IL-13 antibodies for the treatment of atopic dermatitis

Abstract

Provided herein are methods, uses of anti-IL-13 antibodies, such as lebrikizumab, and pharmaceutical compositions for treating atopic dermatitis in pediatric patients. Also provided herein are doses and dosing regimens for methods, and uses of anti-IL-13 antibodies, such as lebrikizumab, for treating atopic dermatitis in pediatric patients.

Description

[Technical field]

[0001] The present invention relates to methods, uses of anti-IL-13 antibodies, such as lebrikizumab, and pharmaceutical compositions for treating atopic dermatitis in pediatric patients. The present invention also relates to doses and dosing regimens for the methods and uses of anti-IL-13 antibodies, such as lebrikizumab, for treating atopic dermatitis in pediatric patients. [Background technology]

[0002] Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease characterized by exudative erythema, dryness, lichenification, and pruritus. It is one of the most common inflammatory skin disorders in developed countries, with a lifetime prevalence of 10%-20% (Deckers et al., PLoS One 2012;7:e39803; Weidinger et al., Lancet 2016;387:1109-22; Weidinger et al., Nature Reviews Disease Primers 2018;4:1). According to estimates from the International Study of Asthma and Allergies in Childhood (ISAAC), AD affects 15%-20% of children and 1%-3% of adults worldwide.

[0003] AD is more common in children than adults and is often first diagnosed in children (Silverberg, Ann Allergy Asthma Immunol. 2019;123(2):144-151). Most cases of AD begin before age 5 (85%) and tend to be associated with allergic sensitization (Bieber et al., N Engl J Med. 2008;358:1483-94; Kim et al., J Am Acad Dermatol. 2016;75(4):681-687.e11; Silverberg and Duran-McKinster, Dermatol Clin. 2017;35:351-363). The prevalence of AD peaks in childhood (estimated 14%), declines in adolescence (approximately 8%), and remains stable through adulthood (6%-8%). AD is a chronic disease. Although AD may spontaneously remit in young children, it is often the first manifestation of a disorder that causes allergic rhinitis, asthma, and food allergies, commonly known as the atopic march (Illi, J Allergy Clin Immunol. 2004;113:925-31; Spergel, Immunol Allergy Clin North Am 2010;30:269-80; Davidson, J Allergy Clin Immunol. 2019 Jan 9.pii:S0091-6749(19)30014-4). Children with moderate to severe AD have an approximately 50% risk of developing asthma and a 75% risk of developing allergic rhinitis (Thomsen, ISRN Allergy 2014;2014:1-7).

[0004] Interleukin (IL)-13 is a key mediator of T-helper type 2 (Th2) inflammation and signals through the heterodimeric receptor IL-4Rα / IL-13Rα1. A summary of several lines of evidence suggests that IL-13 is a major pathogenic component in AD. Increased expression of IL-13 has been consistently reported in AD skin (Tsoi L, et al. Journal of Investigative Dermatology. 2019; 139(7): 1480-1489, Bieber T. Allergy. 2020; 75(1): 54-62), and several reports have suggested a relationship between IL-13 expression and disease severity (La Grutta S, et al., Allergy 60: 391-5

[2005] ). Increased IL-13 has also been reported in the serum of AD patients (Novak N, et al., J Invest Dermatol 2002;119:870-5, WO2016149276), and several studies have reported an increase in IL-13-expressing T cells in the blood of AD patients (Akdis M, et al., J Immunol 1997;159:4611-9, Aleksza M, et al., Br J Dermatol 2002;147:1135-41, La Grutta S, et al., Allergy 2005;60:391-5).

[0005] Therapeutic approaches for AD mainly consist of trigger avoidance, skin moisturization by bathing, and the use of moisturizers and anti-inflammatory therapies such as topical corticosteroids (TCS). In many patients, treatment with TCS provides some symptomatic relief but does not necessarily adequately control the disease. In patients with persistent moderate to severe disease who do not adequately respond to TCS, step-up options include topical calcineurin inhibitors (TCNIs), phototherapy, and immunosuppressants such as oral corticosteroids, cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil. These drugs are not available to patients worldwide. Of these, cyclosporine is approved for the treatment of moderate to severe AD in many European countries, and its use is limited to patients aged 16 years and older (for up to 8 weeks [NEORAL®]). Cyclosporine is a potent immunosuppressant that can result in increased susceptibility to infections and decreased cancer immunosurveillance. Other commonly recognized toxicities of cyclosporine include hypertension and renal and hepatic dysfunction.

[0006] With regard to pediatric AD, systemic immunosuppressants are often not recommended by current guidelines because they are associated with a substantial risk of side effects (Chu, Clin Rev Allergy Immunol. 2021;61(2):114-127). In addition to well-described safety concerns, poor patient satisfaction with treatment is reported to be common; less than one-third of patients report satisfaction with their current treatment regimen.

[0007] There remains an unmet medical need for safe and effective therapies and treatment regimens for moderate to severe AD in children. Summary of the Invention

[0008] Provided herein are methods, uses of anti-IL-13 antibodies, such as lebrikizumab, and pharmaceutical compositions for treating atopic dermatitis in pediatric patients. Also provided herein are doses and dosing regimens for the methods and uses of anti-IL-13 antibodies, such as lebrikizumab, for treating atopic dermatitis in pediatric patients.

[0009] In one aspect, provided herein are methods of treating moderate to severe atopic dermatitis in a patient in need thereof, the methods comprising administering lebrikizumab to the patient, the patient being between 6 months and 12 years of age and weighing at least 6 kilograms (kg). In some embodiments, provided herein are methods of treating moderate to severe atopic dermatitis, the methods comprising selecting a patient having moderate to severe atopic dermatitis, being between 6 months and 12 years of age and weighing at least 6 kg, and administering lebrikizumab to the patient. In some embodiments, the patient is treated for a treatment period of 16 weeks. During the treatment period, lebrikizumab is administered to the patient at a dose and frequency selected based on the patient's weight. In some embodiments, if the patient weighs 40 kg or more, lebrikizumab is administered to the patient at 500 mg in weeks 0 and 2, and 250 mg every two weeks from weeks 4 to 14 (e.g., at weeks 4, 6, 8, 10, 12, 14). In some embodiments, if the patient weighs less than 15 kg to 40 kg, lebrikizumab is administered to the patient at 250 mg in week 0, and 250 mg every four weeks from weeks 2 to 14 (e.g., at weeks 2, 6, 10, 14). In some embodiments, if the patient weighs less than 6 kg to 15 kg, lebrikizumab is administered at 125 mg in week 0 and 125 mg every 4 weeks from week 2 through week 14 (e.g., at weeks 2, 6, 10, and 14).

[0010] In another aspect, provided herein are methods of treating moderate to severe atopic dermatitis in a patient in need thereof, comprising administering lebrikizumab to the patient, wherein the patient is between 12 and 18 years old and weighs less than 40 kg. In some embodiments, provided herein are methods of treating moderate to severe atopic dermatitis, comprising selecting a patient having moderate to severe atopic dermatitis, between 12 and 18 years old, and weighing less than 40 kg, and administering lebrikizumab to the patient. In some embodiments, the patient is treated for a treatment period of 16 weeks. During the treatment period, lebrikizumab is administered to the patient at a dose and frequency selected based on the patient's weight. In some embodiments, if the patient weighs less than 15 kg to 40 kg, lebrikizumab is administered to the patient at 250 mg in week 0 and 250 mg every 4 weeks from week 2 to week 14 (e.g., at weeks 2, 6, 10, 14). In some embodiments, if the patient weighs less than 6 kg to 15 kg, lebrikizumab is administered to the patient at 125 mg in week 0 and 125 mg every 4 weeks from week 2 to week 14 (e.g., at weeks 2, 6, 10, 14).

[0011] In another aspect, provided herein are methods of treating moderate to severe atopic dermatitis, the methods comprising: selecting a patient with moderate to severe atopic dermatitis and weighing less than 6 kg to 15 kg; and administering to the patient lebrikizumab at 125 mg at week 0 and 125 mg once every 4 weeks from week 2 to week 14. In some embodiments, the patient is between 6 months and 12 years old. In some embodiments, the patient is between 12 and 18 years old.

[0012] In another aspect, provided herein are methods of treating moderate to severe atopic dermatitis, the methods comprising: selecting a patient with moderate to severe atopic dermatitis and weighing less than 15 kg to 40 kg; and administering to the patient lebrikizumab at 250 mg at week 0 and 250 mg once every 4 weeks from week 2 to week 14. In some embodiments, the patient is between 6 months and 12 years of age. In some embodiments, the patient is between 12 and 18 years of age.

[0013] In another aspect, provided herein are methods of treating moderate to severe atopic dermatitis, the methods comprising selecting a patient with moderate to severe atopic dermatitis and a body weight of 40 kg or greater, and administering to the patient lebrikizumab at 500 mg at weeks 0 and 2, and 250 mg every two weeks from weeks 4 to 14. In some embodiments, the patient is between 6 months and 12 years of age.

[0014] In some embodiments, the patient has an Eczema Area and Severity Index (EASI) score of 16 or greater, an Investigator Global Assessment (IGA) score of 3 or greater, and more than 10% of body surface area (BSA) affected by atopic dermatitis prior to administration of lebrikizumab. In some embodiments, the patient has had an inadequate response to topical corticosteroids prior to administration of lebrikizumab. In some embodiments, if the patient is 6 years of age or older, the patient has had atopic dermatitis for at least 12 months. In some embodiments, if the patient is 6 months to less than 6 years of age, the patient has had atopic dermatitis for at least 6 months.

[0015] In some embodiments, the method further comprises determining the patient's EASI score after the treatment period, e.g., at week 16. In some embodiments, the EASI score determined after the treatment period, e.g., at week 16, is reduced by 75% or more compared to the EASI score determined before administration of lebrikizumab. In some embodiments, the EASI score determined after the treatment period, e.g., at week 16, is reduced by 90% or more compared to the EASI score determined before administration of lebrikizumab.

[0016] In some embodiments, the methods further include determining the patient's IGA score after the treatment period, e.g., at week 16. In some embodiments, the patient's IGA score determined after the treatment period, e.g., at week 16, is 0 or 1, and the IGA score determined after the treatment period, e.g., at week 16, is reduced by 2 or more points compared to the IGA score determined prior to administration of lebrikizumab.

[0017] In some embodiments, the methods further include determining the patient's pruritus numeric rating scale (NRS) score after the treatment period, e.g., at week 16. In some embodiments, the pruritus NRS score determined after the treatment period, e.g., at week 16, is reduced by 4 or more points compared to the pruritus NRS score determined prior to administration of lebrikizumab.

[0018] In some embodiments, the method further comprises determining one or more of the following characteristics of the patient at week 16: (i) percentage of BSA affected by atopic dermatitis, (ii) DLQI, cDLQI, and / or IDLQI, (iii) PRISM, (iv) SCORAD, (v) PROMIS Anxiety, PROMIS Depression, PROMIS Sleep Disorder, and / or PROMIS Sleep Related Disorder, (vi) POEM, (vii) EQ-5D-Y and / or EQ-5D-5L, (viii) mSQAAQ, (ix) DFI, (x) WPAI-AD-CG.

[0019] In some embodiments, lebrikizumab is administered to a patient subcutaneously. In some embodiments, lebrikizumab is administered to a patient using a subcutaneous administration device, such as a prefilled syringe, a disposable pen injection device, a microneedle device, a microinfuser device, a needleless injection device, or an autoinjector device.

[0020] In another aspect, provided herein is lebrikizumab, or a pharmaceutical composition comprising lebrikizumab, for use in treating moderate to severe atopic dermatitis in a patient aged between 6 months and 12 years and weighing at least 6 kg. Also provided is the use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient aged between 6 months and 12 years and weighing at least 6 kg.

[0021] In another aspect, provided herein is lebrikizumab, or a pharmaceutical composition comprising lebrikizumab, for use in treating moderate to severe atopic dermatitis in a patient between 12 and 18 years of age and weighing less than 40 kg. Also provided is the use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient between 12 and 18 years of age and weighing less than 40 kg.

[0022] In another aspect, provided herein is lebrikizumab, or a pharmaceutical composition comprising lebrikizumab, for use in treating moderate to severe atopic dermatitis in a patient weighing less than 6 kg to 15 kg. Also provided is the use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient weighing less than 6 kg to 15 kg. In some embodiments, lebrikizumab is administered to such a patient at 125 mg in week 0 and 125 mg once every 4 weeks from week 2 to week 14. In some embodiments, the patient is between 6 months and 12 years old. In some embodiments, the patient is between 12 and 18 years old.

[0023] In another aspect, provided herein is lebrikizumab, or a pharmaceutical composition comprising lebrikizumab, for use in treating moderate to severe atopic dermatitis in a patient having a body weight of less than 15 kg to 40 kg. Also provided is the use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient having a body weight of less than 15 kg to 40 kg. In some embodiments, lebrikizumab is administered to such a patient at 250 mg in week 0 and 250 mg once every 4 weeks from week 2 to week 14. In some embodiments, the patient is between 6 months and 12 years of age. In some embodiments, the patient is between 12 and 18 years of age.

[0024] In another aspect, provided herein is lebrikizumab, or a pharmaceutical composition comprising lebrikizumab, for use in treating moderate to severe atopic dermatitis in a patient weighing 40 kg or more. Also provided is the use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient weighing 40 kg or more. In some embodiments, lebrikizumab is administered to such a patient at 500 mg in weeks 0 and 2, and at 250 mg once every two weeks from weeks 4 to 14. In some embodiments, the patient is between 6 months and 12 years of age.

[0025] In some embodiments, the methods, uses, and pharmaceutical compositions described herein further comprise administering to the patient one or more topical corticosteroids. In some embodiments, the topical corticosteroid is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone. In some embodiments, the topical corticosteroid is administered simultaneously with lebrikizumab. [Brief description of the drawings]

[0026] [Figure 1]FIG. 1 is a schematic diagram of the Phase 3 study design (KGBI) described in Example 1. Abbreviations: pts=participants, PK=pharmacokinetics, TCS=topical corticosteroid, V=visit, W=week. Footnotes: a Post-treatment safety follow-up will occur at week 26 (or approximately 12 weeks after the last dose of study intervention). b Participants who complete the study are eligible to enroll in a long-term extension study. "Decision" in the schema indicates an interim PK and safety assessment evaluating the first 30 participants enrolled from cohort 1, prior to enrollment of younger participants from cohort 2. [Diagram 2] Schematic diagram of the Phase 3 study design (KGBJ) described in Example 2. Abbreviations: V = visit, W = week. Footnotes: a Post-treatment safety follow-up will occur at week 62 (or approximately 12 weeks after the last dose of lebrikizumab). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] Provided herein are methods, uses of anti-IL-13 antibodies, such as lebrikizumab, and pharmaceutical compositions for treating atopic dermatitis in pediatric patients. Also provided herein are doses and dosing regimens for the methods and uses of anti-IL-13 antibodies, such as lebrikizumab, for treating atopic dermatitis in pediatric patients.

[0028] In one aspect, provided herein are methods of treating moderate to severe atopic dermatitis in a patient in need thereof, the methods comprising administering lebrikizumab to the patient, the patient being between 6 months and 12 years of age and weighing at least 6 kilograms (kg). In some embodiments, provided herein are methods of treating moderate to severe atopic dermatitis, the methods comprising selecting a patient having moderate to severe atopic dermatitis, being between 6 months and 12 years of age and weighing at least 6 kg, and administering lebrikizumab to the patient. In some embodiments, the patient is treated for a treatment period of 16 weeks. During the treatment period, lebrikizumab is administered to the patient at a dose and frequency selected based on the patient's weight. In some embodiments, if the patient weighs 40 kg or more, lebrikizumab is administered to the patient at 500 mg in weeks 0 and 2, and 250 mg every two weeks from weeks 4 to 14 (e.g., at weeks 4, 6, 8, 10, 12, 14). In some embodiments, if the patient weighs less than 15 kg to 40 kg, lebrikizumab is administered to the patient at 250 mg in week 0, and 250 mg every four weeks from weeks 2 to 14 (e.g., at weeks 2, 6, 10, 14). In some embodiments, if the patient weighs less than 6 kg to 15 kg, lebrikizumab is administered at 125 mg in week 0 and 125 mg every 4 weeks from week 2 through week 14 (e.g., at weeks 2, 6, 10, and 14).

[0029] In another aspect, provided herein are methods of treating moderate to severe atopic dermatitis in a patient in need thereof, comprising administering lebrikizumab to the patient, wherein the patient is between 12 and 18 years old and weighs less than 40 kg. In some embodiments, provided herein are methods of treating moderate to severe atopic dermatitis, comprising selecting a patient having moderate to severe atopic dermatitis, between 12 and 18 years old, and weighing less than 40 kg, and administering lebrikizumab to the patient. In some embodiments, the patient is treated for a treatment period of 16 weeks. During the treatment period, lebrikizumab is administered to the patient at a dose and frequency selected based on the patient's weight. In some embodiments, if the patient weighs less than 15 kg to 40 kg, lebrikizumab is administered to the patient at 250 mg in week 0 and 250 mg once every 4 weeks from week 2 to week 14 (e.g., at weeks 2, 6, 10, 14). In some embodiments, if the patient weighs less than 6 kg to 15 kg, lebrikizumab is administered to the patient at 125 mg in week 0 and 125 mg once every 4 weeks from week 2 to week 14 (e.g., at weeks 2, 6, 10, 14).

[0030] In another aspect, provided herein are methods of treating moderate to severe atopic dermatitis, the methods comprising: selecting a patient with moderate to severe atopic dermatitis and weighing less than 6 kg to 15 kg; and administering to the patient lebrikizumab at 125 mg at week 0 and 125 mg once every 4 weeks from week 2 to week 14. In some embodiments, the patient is between 6 months and 12 years old. In some embodiments, the patient is between 12 and 18 years old.

[0031] In another aspect, provided herein are methods of treating moderate to severe atopic dermatitis, the methods comprising: selecting a patient with moderate to severe atopic dermatitis and weighing less than 15 kg to 40 kg; and administering to the patient lebrikizumab at 250 mg at week 0 and 250 mg once every 4 weeks from week 2 to week 14. In some embodiments, the patient is between 6 months and 12 years of age. In some embodiments, the patient is between 12 and 18 years of age.

[0032] In another aspect, provided herein are methods of treating moderate to severe atopic dermatitis, the methods comprising selecting a patient with moderate to severe atopic dermatitis and a body weight of 40 kg or greater, and administering to the patient lebrikizumab at 500 mg at weeks 0 and 2, and 250 mg every two weeks from weeks 4 to 14. In some embodiments, the patient is between 6 months and 12 years of age.

[0033] In some embodiments, the patient has an Eczema Area and Severity Index (EASI) score of 16 or greater, an Investigator Global Assessment (IGA) score of 3 or greater, and more than 10% of the body surface area (BSA) affected by atopic dermatitis prior to administration of lebrikizumab. In some embodiments, the patient has had an inadequate response to topical corticosteroids prior to administration of lebrikizumab. In some embodiments, if the patient is 6 years of age or older, the patient has had atopic dermatitis for at least 12 months. In some embodiments, if the patient is 6 months to less than 6 years of age, the patient has had atopic dermatitis for at least 6 months.

[0034] In some embodiments, moderate to severe atopic dermatitis can be determined by the American Academy of Dermatology Criteria for the Diagnosis and Assessment of Atopic Dermatitis (Eichenfield et al., J Am Acad Dermatol. 2014;70(2):338-351). Essential features that must be present for a diagnosis of AD include pruritus and acute, subacute, or chronic eczema of typical morphology and age-specific patterns, or a history of chronic or recurrent disease. Age-specific patterns include: involvement of the face, neck, and extensor muscles in infants and children, current or previous flexor involvement in any age group, and sparing of the groin and axillary regions. Key features are seen in most cases and support a diagnosis of AD, including early age onset, atopy (personal and / or family history, and / or IgE reactivity), and dryness. Clinical associations that help suggest a diagnosis of AD, but are too nonspecific to be used to define or detect AD for research and epidemiological studies, include atypical vascular responses such as facial pallor, white dermatographia, and delayed pallor reaction, other local findings such as keratosis pilaris or pityriasis alba or hyperlinear palms or ichthyosis, ocular or periorbital changes, perioral changes or periauricular lesions, and perifollicular accentuation or lichenification or prurigo lesions. The diagnosis of AD also depends on excluding conditions such as scabies, seborrheic dermatitis, contact dermatitis (irritant or allergic), ichthyosis, cutaneous T-cell lymphoma, psoriasis, photosensitive dermatoses, immunodeficiency disorders, or erythroderma of other causes.

[0035] The severity of atopic dermatitis can also be determined by the "Hanifin and Rajka criteria" described in the diagnostic criteria of Hanifin and Rajka described in Acta Derm Venereol (Stockh) 1980; Suppl 92: 44-7, or the "Rajka and Langeland criteria" described in Rajka G and Langeland T, Acta Derm Venereol (Stockh) 1989; 144 (Suppl): 13-4.

[0036] Lebrikizumab is an IgG4 monoclonal antibody that binds human IL-13 with high affinity and blocks IL-13 signaling through the IL-4Ra / IL-13Ra1 heterodimeric receptor. The amino acid sequence of lebrikizumab is provided in Table 1. Lebrikizumab comprises three heavy chain CDRs: HCDR1 of SEQ ID NO: 1, HCDR2 of SEQ ID NO: 2, and HCDR3 of SEQ ID NO: 3, and three light chain CDR3s: LCDR1 of SEQ ID NO: 4, LCDR2 of SEQ ID NO: 5, and LCDR3 of SEQ ID NO: 6. Lebrikizumab comprises a heavy chain variable region (VH) of SEQ ID NO: 7 and a light chain variable region (VL) of SEQ ID NO: 8. Lebrikizumab comprises a heavy chain (HC) of SEQ ID NO: 9 and a light chain (LC) of SEQ ID NO: 10. C-terminal clipping of an IgG antibody can occur when one or two C-terminal amino acids are removed from the heavy chain of an IgG antibody. For example, the C-terminal lysine (K), if present, can be truncated or clipped from the heavy chain. The penultimate glycine can be similarly truncated or clipped from the heavy chain. Modification of the N-terminal amino acid of an IgG can also occur. For example, an N-terminal glutamine (Q) or glutamic acid (E) can spontaneously cyclize to pyroglutamic acid (pE). SEQ ID NO: 9 reflects these potential modifications of the lebrikizumab heavy chain.

[0037] [Table 1]

[0038] Lebrikizumab can be formulated into a pharmaceutical composition suitable for administration to a patient with a suitable carrier or excipient. For example, lebrikizumab can be formulated in a pharmaceutical composition as described in WO 2013 / 066866. The pharmaceutical composition can include 125 mg, 250 mg, or 500 mg of lebrikizumab. In some embodiments, the concentration of lebrikizumab in the pharmaceutical composition is 100 mg / mL to 150 mg / mL, e.g., 125 mg / mL. The pharmaceutical composition can also include 5 mM to 40 mM histidine acetate buffer, pH 5.4 to 6.0. In some embodiments, the pharmaceutical composition further includes a polyol (e.g., a sugar) having a concentration of 100 mM to 200 mM, and / or a surfactant (e.g., polysorbate 20) having a concentration of 0.01% to 0.1%. In one embodiment, the pharmaceutical composition comprises 125 mg / mL lebrikizumab, 20 mM histidine acetate buffer, pH 5.7, 175 mM sucrose, and 0.03% polysorbate 20.

[0039] In some embodiments, lebrikizumab is administered to a patient subcutaneously. In some embodiments, lebrikizumab is administered to a patient using a subcutaneous administration device. The subcutaneous administration device may be selected from a pre-filled syringe, a disposable pen injection device, a microneedle device, a microinfuser device, a needleless injection device, or an auto-injector device. A variety of subcutaneous administration devices, including auto-injector devices, are known in the art and are commercially available. Exemplary devices include, but are not limited to, pre-filled syringes (such as BD HYPAK SCF®, READYFILL™, and STERIFILL SCF™ from Becton Dickinson, CLEARSHOT™ copolymer pre-filled syringes from Baxter, and Daikyo Seiko CRYSTAL ZENITH® pre-filled syringes available from West Pharmaceutical Services), disposable pen injection devices such as the BD Pen from Becton Dickinson, ultra-sharp and microneedle devices (such as INJECT-EASE™ and microinfuser devices from Becton Dickinson, and H-PATCH™ available from Valeritas), and needle-free injection devices (such as BIOJECTOR® and IJECT® available from Bioject, and SOF-SERTER® and patch devices available from Medtronic). In some embodiments, the subcutaneous administration device is an auto-injector device described in WO 2008 / 112472, WO 2011 / 109205, WO 2014 / 062488, and / or WO 2016 / 089864.

[0040] In some embodiments, the patient is treated with lebrikizumab for a treatment period of 12 to 68 weeks, e.g., 12 weeks, 14 weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, 24 weeks, 26 weeks, 28 weeks, 30 weeks, 32 weeks, 34 weeks, 36 weeks, 38 weeks, 40 weeks, 42 weeks, 44 weeks, 46 weeks, 48 ​​weeks, 50 weeks, 52 weeks, 54 weeks, 56 weeks, 58 weeks, 60 weeks, 62 weeks, 64 weeks, 66 weeks, 68 weeks. In some embodiments, the patient is treated with lebrikizumab for a treatment period of 16 weeks. In some embodiments, the patient is treated with lebrikizumab for a treatment period of 52 weeks. In some embodiments, the patient is treated with lebrikizumab for a treatment period of 68 weeks. In some embodiments, the patient is treated with lebrikizumab for a treatment period of 16 weeks, followed by a maintenance period of 52 weeks.

[0041] In some embodiments, lebrikizumab is administered to a patient at a loading dose of 250 mg or 500 mg, followed by subsequent doses of 125 mg or 250 mg for the remainder of the treatment period. The loading dose can be administered to a patient several times (e.g., once or twice) at the beginning of treatment. After the loading dose, lebrikizumab can be administered to a patient at subsequent doses once every 4 weeks or once every 2 weeks. In some embodiments, lebrikizumab is administered at a loading dose of 125 mg at week 0, followed by subsequent doses of 125 mg once every 4 weeks starting at week 2 for the remainder of the treatment period. In some embodiments, lebrikizumab is administered at a loading dose of 250 mg at week 0, followed by subsequent doses of 250 mg once every 4 weeks starting at week 2 for the remainder of the treatment period. In some embodiments, lebrikizumab is administered at a loading dose of 500 mg at weeks 0 and 2, followed by subsequent doses of 250 mg every 2 weeks starting at week 4 for the remainder of the treatment period.

[0042] In some embodiments, lebrikizumab is administered to the patient at a dose and frequency selected based on the patient's weight. In some embodiments, if the patient weighs less than 6 kg to 15 kg, lebrikizumab is administered at 125 mg in week 0 and 125 mg once every 4 weeks starting from week 2 for the remainder of the treatment period. In some embodiments, if the patient weighs less than 15 kg to 40 kg, lebrikizumab is administered to the patient at 250 mg in week 0 and 250 mg once every 4 weeks starting from week 2 for the remainder of the treatment period. In some embodiments, if the patient weighs 40 kg or more, lebrikizumab is administered to the patient at 500 mg in weeks 0 and 2, and 250 mg once every 2 weeks starting from week 4 for the remainder of the treatment period.

[0043] In some embodiments, the treatment period is 16 weeks. In some embodiments, if the patient weighs less than 6 kg to 15 kg, lebrikizumab is administered to the patient at 125 mg in week 0 and 125 mg once every 4 weeks from week 2 to week 14 (e.g., at weeks 2, 6, 10, 14). In some embodiments, if the patient weighs less than 15 kg to 40 kg, lebrikizumab is administered to the patient at 250 mg in week 0 and 250 mg once every 4 weeks from week 2 to week 14 (e.g., at weeks 2, 6, 10, 14). In some embodiments, if the patient weighs 40 kg or more, lebrikizumab is administered to the patient at 500 mg in weeks 0 and 2, and 250 mg every two weeks from week 4 through week 14 (e.g., at weeks 4, 6, 8, 10, 12, and 14).

[0044] During and after the treatment period, the patient may be evaluated for one or more features of the Atopic Dermatitis Disease Severity Measures (ADDSM), which determine certain signs, symptoms, characteristics, or parameters associated with atopic dermatitis and which can be assessed quantitatively or qualitatively.Exemplary ADDSMs include, but are not limited to, the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Body Surface Area (BSA), Severity Scoring of Atopic Dermatitis (SCORAD), Numerical Rating Scale for Pruritus (NRS), Parent-Reported Itch Severity Measure (PRISM), Dermatology Life Quality Index (DLQI) score or children's DLQI (cDLQI) or infants' DLQI (IDLQI), modified Subcutaneous Administration Assessment Questionnaire (mSQAAQ), Patient-Reported Outcomes Measurement Information System (PRAQ), and the Pruritus Assessment and Evaluation System (PAIS). These include the PROMIS Quality of Life Assessment and Treatment System (PROMIS), PROMIS Anxiety, PROMIS Depression, PROMIS Sleep Disorders, PROMIS Sleep-Related Disorders, Patient-Oriented Eczema Measure (POEM), European Quality of Life-5 Dimensions-Youth version (EQ-5D-Y), European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L), Dermatitis Family Impact (DFI), and Work Productivity and Activity Impairment Questionnaire: Atopic Dermatitis Caregiver (WPAI-AD-CG).

[0045] ADDSM can be measured at baseline (before administration of lebrikizumab) and at one or more time points after administration of lebrikizumab. For example, ADDSM can be measured at the end of week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12, week 13, week 14, week 15, week 16, or more after the first treatment with lebrikizumab. The difference between the value of ADDSM at a particular time point after the start of treatment and the value of ADDSM at baseline is used to establish whether there has been an improvement (e.g., a decrease) in ADDSM.

[0046] The "Eczema Area and Severity Index" or "EASI" is an investigator-administered 20-item scale in adults and children that assesses two aspects of AD: the extent of disease in four body regions (head / neck, trunk, upper and lower extremities), and four clinical signs (erythema, edema / papulation, excoriation, and lichenification). Clinical signs are rated for severity on a scale of 0 (absent) to 3 (severe) (Hanifin et al., Exp Dermatol. 2001;10:11-18). Scores are summed for each of the four body regions. The percentage of BSA assigned for each part of the body is 10% for head / neck, 20% for upper extremities, 30% for trunk, and 40% for lower extremities, respectively. Each subtotal score is multiplied by the BSA represented by that region. The multipliers for the region scores differ to reflect the relative proportions of the body regions in young children. In addition, an area score of 0 to 6 is assigned to each body region depending on the percentage of AD-affected skin in that area: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each body area score is multiplied by the affected area. The resulting EASI ranges from 0 to 72 points, with the highest score indicating a worse severity of AD. The recall period for this scale is the present time.

[0047] The "Investigator Global Assessment" or "IGA" is an investigator-administered single-item scale to assess the severity of participants' AD (Simpson E, et al. J Am Acad Dermatol. 2020;83(3):839-846). The IGA consists of a 5-point scale ranging from 0 (no abnormalities) to 4 (severe), with scores selected using the descriptor that best describes the overall appearance of the lesion at a given time point (see Table 2).

[0048] [Table 2]

[0049] Body surface area (BSA) is an investigator-reported assessment that estimates the extent of a participant's AD disease or skin involvement. BSA is expressed as a percentage of total body surface and reported by body location. BSA is determined by the investigator using the approximately 1% BSA rule on the palm of the participant's hand.

[0050] The pruritus numerical rating scale (NRS) is a participant-administered 11-point scale used by participants aged 6 years and older to rate the severity of the participant's worst itch over the past 24 hours, with 0 indicating "no itch" and 10 indicating "worst itch imaginable." Ratings are recorded daily by participants (Yosipovitch et al., Br J Dermatol. 2019;181(4):761-769). The pruritus NRS measures the itch most commonly felt by participants with AD. Thus, the questions are designed for self-report. When possible, participants should read and complete the questions alone. If necessary, a caregiver (parent or other person) can read the questions and answer options to the person with AD. However, it is important that the participant's selected answers to the questions are entered directly into the questions. Caregivers should not influence or question the answers given by the person with AD. The pruritus NRS baseline mean score for maximum itch intensity is determined based on daily scores for the 7 days immediately prior to randomization. A minimum of 4 scores out of 7 days are required to calculate a baseline mean score.

[0051] The "Parent-Reported Itch Severity Scale" or PRISM is a single-item parent / caregiver-administered scale that reports the overall severity of a child's itch. Parents / caregivers report the overall severity of their child's itch based on the child's observed behavior over the past 24 hours. Response options range from "no itch," "mild," "moderate," "severe," and "very severe." The PRISM is completed by parents / caregivers for participants under the age of 6. Responses are required on a minimum of 4 out of 7 days to calculate a baseline mean response.

[0052] The "Scoring Severity of Atopic Dermatitis" or "SCORAD" index is an investigator- and participant-administered nine-item assessment evaluating three aspects: (i) the extent of AD (1 item) is assessed by the investigator as a percentage of each defined body area and reported as the sum of all areas (maximum score is 100%); (ii) the severity of six specific symptoms of AD: erythema, edema / papulation, oozing / crusting, excoriation, lichenification and dryness (6 items) is assessed by the investigator using a four-point scale (i.e., none=0, mild=1, moderate=2, severe=3) with a maximum possible total of 18 points; (iii) subjective symptoms of pruritus and sleep loss (2 items) are assessed by the participant via a 10 cm visual analogue scale. Symptoms (itchiness and insomnia) are recorded by the participant or caregiver on a visual analog scale, with 0 being no symptoms and 10 being the worst symptoms imaginable, with a maximum possible score of 20. For participants under 8 years of age, the SCORAD is completed by the caregiver. The formula for the SCORAD index is A / 5+7B / 2+C. In this formula, A is defined as range (0-100), B is defined as severity (0-18), and C is defined as subjective symptoms (0-20). The maximum possible SCORAD score calculated based on the above three aspects is 103. Higher scores indicate a worse or more severe condition (Stalder and Taieb, Dermatology. 1993; 186(1):23-31; Oranje et al., Br J Dermatol. 2007; 157(4):645-648; Schram et al., Allergy. 2012; 67(1):99-106). Recall periods are the current time for extent and intensity and the average of the last 3 days / nights for subjective symptoms of AD.

[0053] The Dermatology Quality of Life Index (DLQI) is a participant-administered, 10-item, validated (Quality of Life, QoL) questionnaire in adults covering six domains including symptoms and emotions, daily activities, leisure, work and school, relationships, and treatment. The recall period for this scale is over the "last week." Response categories include "not at all," "a little," "a lot," and "very much," with corresponding scores of 0, 1, 2, and 3, respectively, with unanswered (or "not applicable") responses scored as 0. Scores range from 0 to 30, with higher scores indicating greater impairment of QoL. A DLQI total score of 0–1 is considered not to affect participants' health-related QoL (Hongbo et al., J Invest Dermatol. 2005;125(4):659-664), and a 4-point change from baseline is considered the threshold for the minimal clinically important difference (Khilji et al. 2002, Br J Dermatol. 2002;147(suppl62):25-54, Basra et al., Dermatology. 2015;230(1):27-33). The recall period for the DLQI is the past week. Participants aged 4–17 years should complete the pediatric DLQI (cDLQI) questionnaire and continue to complete the cDLQI for the duration of the study (Lewis-Jones MS, Finlay AY. Br J Dermatol. 1995;132:942-949). For children under 4 years of age (i.e. up to 3 years 11 months of age), caregivers should complete the infant DLQI (IDQOL) questionnaire and continue to complete the IDQOL for the duration of the study (Lewis-Jones et al., Br J Dermatol. 2001;144(1):104-110; Basra et al., Br J Dermatol. 2013;169(4):760-768).

[0054] The modified Subcutaneous Administration Assessment Questionnaire (mSQAAQ) uses 10 questions that provide an assessment of the ease and reliability of use, e.g., acceptability and tolerability, of the use of a device to administer a subcutaneous injection of an investigational drug. Participants' parents / caregivers respond to 10 questionnaire items regarding characteristics related to the use of the administration device using a 7-point Likert scale ("strongly disagree" to "strongly agree") immediately after completing the injection. Characteristics assessed include ease of learning how to use the device, ease of use, ease of storing the device, confidence in ability to use the device, and confidence in completing the injection (Callis Duffin et al. 2016). Parents / caregivers complete a paper questionnaire.

[0055] PROMIS (Patient-Reported Outcomes Measurement Information System) is a set of person-centered scales that assess and monitor physical, mental, and social health in adults and children (PROMIS WWW). The PROMIS scales include short versions of anxiety and depression, which assess participants' symptoms over the past week. It can be used in the general population and in individuals living with chronic conditions.

[0056] The PROMIS Anxiety scale assesses the following items: self-reported fear (fear, panic), distressing anxiety (worry, fear), hyperarousal (tension, nervousness, restlessness), and physical symptoms related to arousal (palpitations, dizziness) (PROMIS Anxiety 2019, available at https: / / www.healthmeasures.net / images / PROMIS / manuals / PROMIS_Anxiety_Scoring_Manual.pdf). The PROMIS Anxiety Short Form (8 questions, 8a v2.0) is available for children self-report (ages 8-18 years) and for parents / caregivers acting as proxy reporters for children (younger ages 5 years and older). Children under 5 years of age do not complete this assessment. Both the children's self-report and proxy-report versions assess anxiety "in the past 7 days." Response options range from 1=never to 2=rarely, 3=sometimes, 4=often, and 5=almost always. The total raw score was converted to a T-score, with higher scores representing greater anxiety.

[0057] The PROMIS Depression scale assesses the following items: self-reported negative mood (sadness, guilt), self-view (self-criticism, feelings of worthlessness), social cognition (loneliness, interpersonal alienation), and diminished positive affect and engagement (loss of interest, meaning, and purpose) (PROMIS Depression 2019, available at https: / / www.healthmeasures.net / images / PROMIS / manuals / PROMIS_Depression_Scoring_Manual.pdf). PROMIS Depression Short Forms (8a v2.0 and 6a v2.0) are available for child self-report (ages 8-18 years) and for parents / caregivers who act as proxy reporters for children (younger ages 5 years and older). Children under 5 years of age do not complete this assessment. Both the child self-report and proxy-report versions assess depression "in the past 7 days." Response options range from 1=never to 2=rarely, 3=sometimes, 4=often, and 5=almost always. Total raw scores were converted to T scores, with higher scores representing greater depression.

[0058] The PROMIS Sleep Disorders instrument assesses self-reported perceptions of sleep quality, sleep depth, and sleep-related restoration. This includes perceived difficulties and concerns about falling asleep or staying asleep, and perceptions of sleep adequacy and satisfaction. The Short Sleep Disorders is universal, not disease-specific. It assesses sleep disturbances over the past 7 days. This measurement is administered wherever mobility is possible. The PROMIS Pediatric Short-Form Sleep Disorders (8 questions, 8a v1) is available for child self-report (ages 8-18 years) and for parents / caregivers who act as proxy reporters for children (younger ages 5 years and older). Children under 5 years of age do not complete this assessment. Both the child self-report and proxy-report versions assess anxiety "in the past 7 days." Response options range from 1=never to 2=rarely, 3=sometimes, 4=often, and 5=almost always. The total raw score was converted to a T-score, with higher scores representing greater anxiety (Yu L et al., Behav Sleep Med. 2011;10(1):6-24).

[0059] The PROMIS Sleep-Related Disorders item bank focuses on self-reported perceptions of alertness, sleepiness, and fatigue during normal waking hours, as well as perceived impairments during wakefulness related to sleep problems or impaired wakefulness. Sleep-Related Disorders measures function within the context of alertness, sleepiness, and overall sleep-wake function. The short version of Sleep-Related Disorders is universal, not disease-specific. It assesses sleep-related disorders over the past 7 days. This measurement is administered wherever mobility is possible. PROMIS Pediatric Short Version-Sleep-Related Disorders (8 questions, 8a v1) is available for pediatric self-report (ages 8-18 years) and for parents / caregivers who act as proxy reporters for their children (younger ages 5 years and older). Children under 5 years of age do not complete this assessment. Both the pediatric self-report and proxy-report versions assess anxiety "in the past 7 days." Response options range from 1=never to 2=rarely, 3=sometimes, 4=often, and 5=almost always. The total raw score was converted to a T-score, with higher scores representing greater anxiety (Yu L et al., Behav Sleep Med. 2011;10(1):6-24).

[0060] The European Quality of Life-Five Dimensions-Young People version (EQ-5D-Y) is a widely used generic questionnaire that assesses health status "today" (The EuroQol Group). The EQ-5D-Y is self-administered for pediatric participants aged 8 years and older, and completed by a parent / caregiver (proxy) for children aged 4-8 years. The assessment is not completed for children under 4 years of age, as per the developer's recommendation. The questionnaire consists of two parts. The first part assesses five dimensions with three possible response levels (no problems, some problems, or many problems): mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. This part of the EQ-5D-Y can be used to generate a health status index score, which is often used to calculate quality-adjusted life years for use in health economic analyses. A health status index score is calculated based on responses to the three dimensions, providing a single value on a scale ranging from less than 0 (zero being a health state equivalent to death and negative values ​​being rated as worse than death) to 1 (perfect health), with higher scores indicating better health utility values. The second part of the questionnaire consists of a visual analogue scale on which participants rate their perceived health state from 0 ("the worst health you can imagine") to 100 ("the best health you can imagine"). Published studies by EuroQol group members have shown evidence of the feasibility, reliability, and validity of the instrument (Ravens-Sieberer et al., Qual Life Res. 2010;19(6):887-897).

[0061] The European Quality of Life-Five Dimensions-Five Levels (EQ-5D-5L, EuroQol Research Foundation) is a standardized five-item self-administered instrument for use as a measure of health outcomes. It provides a simple descriptive profile and a single index value for health status that can be used in clinical and economic evaluations of health care as well as population health surveys. The European Quality of Life-Five Dimensions-Five Levels assesses five dimensions of health: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. The 5L version scores each dimension with five levels: no problems, slight problems, moderate problems, serious problems, and unable to perform / extreme problems. A total of 3125 health states are possible. In addition to the health profile, a single health state index value can be derived based on a formula that weights each of the levels in each dimension. This index value ranges from less than 0 (where 0 is a health state equivalent to death and negative values ​​are rated as worse than death) to 1 (perfect health). In addition, the EQ visual analogue scale scores the respondent's self-rated health on a vertically graduated (0–100) visual analogue scale. Participants rate his / her perceived health from 0 (worst imaginable health) to 100 (best imaginable health). Together with the health status data, it provides a composite picture of the respondent's health status.

[0062] The Patient-Oriented Eczema Scale (POEM) is a caregiver-administered, seven-item scale that assesses disease severity in children and adults. Participants answer questions about the frequency of seven symptoms (itching, sleep disturbance, bleeding, weeping / oozing, cracking, peeling, and dryness / chapping) over the past week. Response categories include "none," "1-2 days," "3-4 days," "5-6 days," and "every day," with corresponding scores of 0, 1, 2, 3, and 4, respectively. Scores range from 0 to 28, with higher total scores indicating greater severity (Charman et al., Arch Dermatol. 2004;140(12):1513-1519). Higher scores indicate poorer quality of life. Caregivers are expected to complete all assessments of the POEM, even if participants reach adult age during the study period.

[0063] The Dermatitis Family Impact (DFI) questionnaire is a caregiver-administered 10-question validated QoL questionnaire designed to assess the impact of AD on the QoL of parents and family members of children with AD (Lawson et al., Br J Dermatol. 1998;138(1):107-113; Dodington et al., Br J Dermatol. 2013;169(1):31-46). The recall period is over the "last week". Response options include "not at all", "a little", "quite a bit", and "very much", with corresponding scores of 0, 1, 2, and 3, respectively. Scores range from 0 to 30, with higher scores indicating greater impairment of QoL. Caregivers are expected to complete all assessments of Dermatitis Family Impact even if participants reach adult age during the study period.

[0064] The Work Productivity and Activity Impairment Questionnaire: Atopic Dermatitis Caregiver (WPAI-AD-CG) assesses the impact of the participant's AD on the parent / caregiver's work productivity over the past 7 days. The WPAI-AD-CG consists of six items categorized into four domains: absenteeism (work time lost), sickness work (impairment at work / reduced effectiveness at work), work productivity loss (overall work impairment / absenteeism and sickness work), and activity impairment. Scores are calculated as a disability percentage (Reilly et al., Pharmacoeconomics. 1993;4(5):353-365), with higher scores indicating greater impairment and less productivity. Caregivers are expected to complete all assessments of the WPAI-AD-CG, even if the participant reaches adult age during the study period.

[0065] In some embodiments, the patient's EASI score is determined after a treatment period, e.g., at week 16. In some embodiments, the patient's EASI score determined after a treatment period, e.g., at week 16, is reduced by 50% or more compared to the EASI score determined before administration of lebrikizumab, meaning that the patient has achieved "EASI50". In some embodiments, the patient's EASI score determined after a treatment period, e.g., at week 16, is reduced by 75% or more compared to the EASI score determined before administration of lebrikizumab, meaning that the patient has achieved "EASI75". In some embodiments, the patient's EASI score determined after a treatment period, e.g., at week 16, is reduced by 90% or more compared to the EASI score determined before administration of lebrikizumab, meaning that the patient has achieved "EASI90".

[0066] In some embodiments, the patient's IGA score is determined after the treatment period, e.g., at week 16. In some embodiments, the patient's IGA score determined after the treatment period, e.g., at week 16, is 0 or 1, and the IGA score determined after the treatment period, e.g., at week 16, is reduced by 2 or more points compared to the IGA score determined prior to administration of lebrikizumab.

[0067] In some embodiments, the patient's pruritus NRS score is determined after the treatment period, e.g., at week 16. In some embodiments, the patient's pruritus NRS score determined after the treatment period, e.g., at week 16, is reduced by 4 or more points compared to the pruritus NRS score determined prior to administration of lebrikizumab.

[0068] In some embodiments, one or more of the following patient characteristics are determined after the treatment period, e.g., at week 16: (i) percentage of BSA affected by atopic dermatitis, (ii) DLQI, cDLQI, and / or IDLQI, (iii) PRISM, (iv) SCORAD, (v) PROMIS Anxiety, PROMIS Depression, PROMIS Sleep Disorder, and / or PROMIS Sleep-Related Disorder, (vi) POEM, (vii) EQ-5D-Y and / or EQ-5D-5L, (viii) mSQAAQ, (ix) DFI, (x) WPAI-AD-CG.

[0069] In another aspect, provided herein is lebrikizumab, or a pharmaceutical composition comprising lebrikizumab, for use in treating moderate to severe atopic dermatitis in a patient aged between 6 months and 12 years and weighing at least 6 kg. Also provided is the use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient aged between 6 months and 12 years and weighing at least 6 kg.

[0070] In another aspect, provided herein is lebrikizumab, or a pharmaceutical composition comprising lebrikizumab, for use in treating moderate to severe atopic dermatitis in a patient between 12 and 18 years of age and weighing less than 40 kg. Also provided is the use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient between 12 and 18 years of age and weighing less than 40 kg.

[0071] In another aspect, provided herein is lebrikizumab, or a pharmaceutical composition comprising lebrikizumab, for use in treating moderate to severe atopic dermatitis in a patient weighing less than 6 kg to 15 kg. Also provided is the use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient weighing less than 6 kg to 15 kg. In some embodiments, lebrikizumab is administered to such a patient at 125 mg in week 0 and 125 mg once every 4 weeks from week 2 to week 14. In some embodiments, the patient is between 6 months and 12 years old. In some embodiments, the patient is between 12 and 18 years old.

[0072] In another aspect, provided herein is lebrikizumab, or a pharmaceutical composition comprising lebrikizumab, for use in treating moderate to severe atopic dermatitis in a patient having a body weight of less than 15 kg to 40 kg. Also provided is the use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient having a body weight of less than 15 kg to 40 kg. In some embodiments, lebrikizumab is administered to such a patient at 250 mg in week 0 and 250 mg once every 4 weeks from week 2 to week 14. In some embodiments, the patient is between 6 months and 12 years of age. In some embodiments, the patient is between 12 and 18 years of age.

[0073] In another aspect, provided herein is lebrikizumab, or a pharmaceutical composition comprising lebrikizumab, for use in treating moderate to severe atopic dermatitis in a patient weighing 40 kg or more. Also provided is the use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient weighing 40 kg or more. In some embodiments, lebrikizumab is administered to such a patient at 500 mg in weeks 0 and 2, and at 250 mg once every two weeks from weeks 4 to 14. In some embodiments, the patient is between 6 months and 12 years of age.

[0074] In some embodiments, the methods, uses, and pharmaceutical compositions described herein further comprise administering one or more topical corticosteroids (TCS) to the patient. Exemplary topical corticosteroids include, but are not limited to, triamcinolone acetonide, hydrocortisone, and a combination of triamcinolone acetonide and hydrocortisone. Triamcinolone acetonide is typically formulated in a cream at a concentration of 0.1%, and hydrocortisone is typically formulated in a cream at a concentration of 1% or 2.5%. Certain topical corticosteroids, such as, for example, betamethasone dipropionate, clobetasol propionate, diflorasone acetate, fluocinonide, and halobetasol propionate, are considered to be highly potent. Certain topical corticosteroids, such as, for example, amcinonide, desoximetasone, halcinonide, and triamcinolone acetonide, are considered to be highly potent. Certain topical corticosteroids, such as, for example, betamethasone valerate, clocortolone pivalate, fluocinolone acetonide, flurandrenolide, fluocinonide, fluticasone propionate, hydrocortisone butyrate, hydrocortisone valerate, mometasone furoate, and prednicarbate, are considered to be of medium potency. Certain topical corticosteroids, such as, for example, alclometasone dipropionate, desonide, and hydrocortisone, are considered to be of low potency. TCS can be applied to the affected area once a day, twice a day, three times a day, or as needed. TCS use can be recorded using a diary. In some embodiments, the patient is inadequately controlled by topical corticosteroids prior to administration of lebrikizumab. In some embodiments, the topical corticosteroid is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone. In some embodiments, the topical corticosteroid is administered simultaneously or sequentially with lebrikizumab. In some embodiments, the topical corticosteroid is administered simultaneously with lebrikizumab.

[0075] As used herein, the terms "a," "an," "the," and similar terms as used in the context of this disclosure (particularly in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated or clearly contradicted by context.

[0076] The term "about" as used herein means sufficiently close to the stated numerical value, for example, ±10% of the stated numerical value.

[0077] As used herein, the term "antibody" refers to an immunoglobulin molecule that binds to an antigen. Antibody embodiments include monoclonal, polyclonal, human, humanized, chimeric, or conjugated antibodies. The antibody may be of any class (e.g., IgG, IgE, IgM, IgD, IgA) and any subclass (e.g., IgG1, IgG2, IgG3, IgG4).

[0078] An exemplary antibody is an immunoglobulin G (IgG) type antibody composed of four polypeptide chains: two heavy chains (HC) and two light chains (LC) cross-linked via interchain disulfide bonds. The amino-terminal portion of each of the four polypeptide chains contains a variable region of about 100-125 or more amino acids that is primarily responsible for antigen recognition. The carboxy-terminal portion of each of the four polypeptide chains contains a constant region that is primarily responsible for effector function. Each heavy chain is composed of a heavy chain variable region (VH) and a heavy chain constant region. Each light chain is composed of a light chain variable region (VL) and a light chain constant region. The IgG isotype can be further divided into subclasses (e.g., IgG1, IgG2, IgG3, and IgG4).

[0079] The VH and VL regions can be further subdivided into hypervariable regions, called complementarity determining regions (CDRs), interspersed with more conserved regions, called framework regions (FRs). The CDRs are exposed on the surface of the protein and are the regions of the antibody that are important for antigen-binding specificity. Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. Herein, the three CDRs of the heavy chain are referred to as "HCDR1, HCDR2, and HCDR3" and the three CDRs of the light chain are referred to as "LCDR1, LCDR2, and LCDR3". The CDRs contain most of the residues that form specific interactions with the antigen.The assignment of amino acid residues to CDRs can be performed using the methods described in Kabat (Kabat et al., "Sequences of Proteins of Immunological Interest," National Institutes of Health, Bethesda, Md. (1991)), Chothia (Chothia et al., "Canonical structures for the hypervariable regions of immunoglobulins," Journal of Molecular Biology, 196, 901-917 (1987), Al-Lazikani et al., "Standard conformations for the canonical structures of immunoglobulins," Journal of Molecular Biology, 273, 927-948 (1997)), North (North et al., "A New Clustering of Antibody CDR Loop Conformations," Journal of Molecular Biology, 406, 228-256 (2011)), or IMGT (the international ImMunoGeneTics This can be done according to well-known schemes, including those described in the Imgt.RTM. database, available at www.imgt.org, see Lefranc et al., Nucleic Acids Res. 1999;27:209-212.

[0080] As used herein, the terms "bind" and "binds", unless otherwise specified, are intended to mean the ability of a protein or molecule to form a chemical bond or attractive interaction with another protein or molecule, resulting in proximity of the two proteins or molecules as determined by common methods known in the art.

[0081] The term "flare" as used herein refers to an increase in signs and / or symptoms that leads to an escalation of therapy, which may be an increase in dosage, a switch to a higher potency class of drug, or the initiation of another drug.

[0082] The term "human IL-13" refers to human interleukin 13 (also known as P600), an immunoregulatory cytokine produced primarily by activated Th2 cells. There are two known human IL-13 isoforms: isoform a and isoform b. As used herein, the term "human IL-13" refers collectively to all human IL-13 isoforms. The amino acid sequence of human IL-13 isoform a can be found at NCBI accession number NP_002179.2. The amino acid sequence of human IL-13 isoform b can be found at NCBI accession number NP_001341922.1.

[0083] As used herein, the term "inadequate response" refers to the failure to achieve good disease control of atopic dermatitis (e.g., failure to achieve an IGA≦2 or EASI 75) after use of treatment for the period recommended by the product prescribing information, or the occurrence of atopic dermatitis flares during treatment.

[0084] The term "intolerance" as used herein refers to unacceptable toxicity (e.g., elevated creatinine, elevated liver function tests, uncontrolled hypertension, anesthesia, headache, nausea, hirsutism) or the need for a drug in a dose or for a duration greater than that specified in the prescribing information.

[0085] As used herein, the term "patient" refers to a human patient.

[0086] As used herein, the term "topical corticosteroids" or "TCS" includes topical corticosteroids of groups I, II, III, and IV. According to the World Health Organization's Anatomical Therapeutic Chemical (ATC) Classification System, corticosteroids are classified as weak (group I), moderately potent (group II), and potent (group III), and very potent (group IV) based on their activity relative to hydrocortisone. Group IV TCS (very potent) are up to 600 times more potent than hydrocortisone and include clobetasol and halcinonide. Group III TCS (potent) are 50-100 times more potent than hydrocortisone and include, but are not limited to, betamethasone valerate, betamethasone dipropionate, diflucortolone valerate, hydrocortisone-17-butyrate, mometasone furoate, and methylprednisolone aceponate. Class II TCS (moderately potent) are 2-25 times more potent than hydrocortisone and include, but are not limited to, clobetasone butyrate and triamcinolone acetonide. Class I TCS (weak or mild) include hydrocortisone, prednisolone, and methylprednisolone.

[0087] As used herein, "treatment" or "treating" refers to any process that may slow, control, retard or stop the progression of a disorder or disease disclosed herein, or ameliorate the symptoms of the disorder or disease, but does not necessarily indicate the complete elimination of all symptoms of the disorder or disease. Treatment includes the administration of a protein or nucleic acid or vector or composition for the treatment of a disease or condition in a patient, particularly a human. EXAMPLES

[0088] Example 1. A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lebrikizumab Compared to Placebo in Participants Aged 6 Months to Less Than 18 Years with Moderate to Severe Atopic Dermatitis (KGBI) This is a randomized, double-blind, placebo-controlled, phase 3 study to evaluate the efficacy, safety, and pharmacokinetics of lebrikizumab in participants aged 6 months to <18 years with moderate to severe AD. The study design is shown in Figure 1. Participants will be divided into two cohorts. Participants in cohort 1 will be aged 6 months to <18 years, including 12 years to <18 years, weighing <40 kg, and 6 years to <12 years, who may weigh 40 kg or more. Participants in cohort 2 will be aged 6 months to <6 years, including 2 years to <6 years, and 6 months to <2 years.

[0089] Enrollment in the study will be staggered by age. Older participants in Cohort 1 will be enrolled in the study first. An interim analysis will evaluate PK and safety parameters from the first 30 participants from Cohort 1 who complete Week 16 (or discontinue early) before enrolling younger participants in Cohort 2.

[0090] Objectives and Evaluation Items: The following primary, secondary, and exploratory objectives and endpoints will be assessed for this study: Statistical analyses of the primary and key secondary endpoints will be performed.

[0091] [Table 3-1]

[0092] [Table 3-2]

[0093] Study design: The study has four treatment periods: Study Periods I-IV. In Study Period I, appropriate informed consent and assent forms will be signed before any study procedures are performed. The investigator will review symptoms, risk factors, medical history, vaccination history, concomitant medications, and other inclusion and exclusion criteria to confirm eligibility. In Study Period II, standardized TCS treatment will be initiated for all participants and continued until the end of the study.

[0094] Study Period III is the double-blind treatment period, during which eligible participants are randomly assigned in a 2:1 ratio to receive either lebrikizumab or placebo. The lebrikizumab dose will be selected based on the participant's weight (see Table 4).

[0095] [Table 4]

[0096] Study Period IV is the post-treatment safety follow-up period. For participants who discontinue the study early or who complete the study through week 16 but do not enroll in the long-term extension study, a safety follow-up assessment will occur 12 weeks after the last dose for final clinical and safety evaluations. Participants who complete the study through week 16 without requiring the use of systemic rescue medications are eligible to enroll in the long-term extension study to evaluate the long-term safety of lebrikizumab.

[0097] Patient Population: Approximately 300 participants will be enrolled and randomized in a 2:1 ratio (200 participants:100 participants) to lebrikizumab or placebo.

[0098] Inclusion Criteria: Patients eligible for inclusion in this study must meet all of the following criteria: 1. Age and weight requirements: (1) 6 months to under 12 years old and weighing at least 6 kg, or (2) 12 years to under 18 years old and weighing less than 40 kg. 2. Have been diagnosed with AD prior to screening, as described by the American Academy of Dermatology criteria, for at least (1) 12 months if the participant is 6 years of age or older, or (2) 6 months if the participant is 6 months to <6 years of age (Eichenfield et al., J Am Acad Dermatol. 2014;70(2):338-351). 3. EASI score ≥ 16 at screening and baseline visits. 4. IGA score ≥ 3 (on a scale of 0 [normal] to 4 [severe]) at screening and baseline visits. 5. AD-related body surface area (BSA) ≥ 10% at screening and baseline visits. 6. History of inadequate response to treatment with topical medications. Inadequate response is defined as failure to achieve stable long-term disease control within 6 months of screening after use of at least moderate potency TCS for at least 4 weeks or the maximum period recommended by the product prescribing information (e.g., 14 days for extra-strength TCS), whichever is shorter. 7. Willing and able to comply with all clinic visits and study-related procedures and questionnaires. 8. For female participants of childbearing potential, remain abstinent or use highly effective contraception. 9. A parent or legal guardian must be able to read, understand, and give written informed consent for their child to participate in this study.

[0099] Exclusion Criteria: Participants will be excluded from the study if any of the following criteria apply: 1. Currently enrolled in, or has participated within the past 8 weeks in, a clinical study involving an investigational intervention or any other type of medical research that is deemed scientifically or medically incompatible with this study. 2. Treatment prior to the Baseline Visit with: a. Investigational drug for 8 weeks or less or 5 half-lives, whichever is longer. b. Dupilumab within 8 weeks. NOTE: Enrollment of participants with prior use of dupilumab will be limited to less than 20%. c. B-cell depleting biologics, including rituximab, for up to 6 months or until lymphocyte and CD19+ lymphocyte counts return to normal, whichever is longer. d. Other biological agents with a half-life (if known) or within 16 weeks, whichever is longer. 3. Previously randomized in any other study investigating lebrikizumab. 4. Have experienced hypersensitivity to any of the active substances or excipients. 5. Treatment with topical investigational medication within 2 weeks prior to the baseline visit. 6. Have had significant adverse reactions to TCS, such as intolerance to treatment, hypersensitivity reactions, significant skin atrophy, and systemic effects, as assessed by the investigator or treating physician that would prevent further use during the study. 7. Treatment with any of the following medications within 4 weeks prior to the Baseline Visit, or any condition that, in the opinion of the Investigator, is likely to require such treatment during the first 4 weeks of study treatment: a. Immunosuppressive / immunomodulatory medications (e.g., systemic corticosteroids, cyclosporine, mycophenolate mofetil, IFN-g, JAK inhibitors, azathioprine, methotrexate). b. Phototherapy and photochemotherapy for AD. 8. Regular use of tanning booths / parlors (>2 visits per week) within 4 weeks of the screening visit. 9. Use of cannabis or cannabinoids for the treatment of pruritus, pain, and AD. 10. I am currently receiving increased doses of allergen immunotherapy (allergy injections). 11. Have received Bacillus Calmette-Guerin vaccination or treatment within 4 weeks prior to randomization. 12. Has received any live vaccine (i.e., live attenuated vaccine) within 4 weeks prior to randomization or intends to receive a live vaccine during the study. 13. Have a current or recent acute active infection requiring treatment with a systemic antibiotic, antiviral, anthelmintic, antiprotozoal, or antifungal agent within 2 weeks prior to screening; by the time of the randomization visit, participants must have no symptoms or signs of confirmed or suspected infection and must have completed any appropriate anti-infective treatment. 14. Have had any of the following types of infections within 3 months of screening or developed any of these infections before baseline: a. Severe (requiring hospitalization and / or intravenous or equivalent oral antibiotic treatment); b. Opportunistic (as defined by Winthrop et al., Ann Rheum Dis. 2015;74(12):2107-2116). Note: Shingles is considered active and ongoing until all vesicles have dried and crusted. c. Recurrent (including but not limited to recurrent cellulitis or chronic osteomyelitis). 15. Having HIV infection. 16. Have current or chronic infection with HBV, i.e. are positive for HBsAg and / or positive for HBV DNA. 17. Currently have infection with HCV, i.e., are positive for HCV RNA. 18. Known active tuberculosis infection. 19. Have known active internal parasitic infections or are at high risk of these infections. 20. Has a history or presence of any underlying disease or surgical, physical, psychological, or medical condition that, in the opinion of the Investigator, potentially affects participant safety within the study or interferes with the interpretation of the data. 21. Have any of the following specific abnormalities on screening laboratory tests: a. AST or ALT ≥ 2 × upper limit of normal (ULN) b. ALP ≥ 2 × ULN (Note: Participants may be allowed to enroll if they have no other evidence of liver, bone, or other abnormalities, but cases must be reviewed by a medical monitor prior to enrollment and deemed not clinically significant). c. Total bilirubin ≥ 1.5 x ULN (Note: Participants may be allowed to enroll if they have no other evidence of hepatic or other abnormalities, but cases must be reviewed by a medical monitor prior to enrollment and determined to be not clinically significant). d. Total white blood cell count <2500 cells / μL (<2.50 × 10 3 / μL or <2.50GI / L) 22. Uncontrolled chronic disease that may require bursts of oral corticosteroids. 23. Uncontrolled asthma defined by: Use of systemic steroids (oral or injected) for asthma symptoms in the past 6 months, or b. Emergency room, hospital, urgent care, or physician visit for uncontrolled asthma symptoms (cough, shortness of breath, chest tightness, wheezing) in the past six months; or c. Use of a rescue inhaler or nebulizer more than twice per week for non-exercise related asthma symptoms for at least 1 month (past 6 months); or d. Waking up at night due to asthma symptoms (coughing, wheezing, shortness of breath) more than twice a month 24. Have clinically significant laboratory results outside the reference range at the Screening visit, in the opinion of the Investigator. 25. Presence of cutaneous comorbidities that may interfere with study evaluation. 26. Has a history of chronic alcohol abuse, intravenous drug abuse, or other illicit drug abuse within 2 years prior to screening. 27. History of malignancy, including mycosis fungoides, within 5 years prior to the screening visit. (Exceptions: completely treated intraepithelial carcinoma of the cervix or completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin. 28. Pregnant or breastfeeding, or planning to become pregnant or breastfeed during the study. 29. In the opinion of the investigator, not suitable for inclusion in the study.

[0100] Example 2. A Phase 3, Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety of Lebrikizumab in Participants Aged 6 Months to Under 18 Years with Moderate to Severe Atopic Dermatitis (KGBJ) This open-label Phase 3 study is designed to evaluate the long-term safety of lebrikizumab in participants aged 6 months to less than 18 years with moderate to severe atopic dermatitis. Participants who completed the KGBI (see Example 1) study through week 16 without requiring the use of systemic rescue medications are eligible to enroll in this study, KGBJ.

[0101] Objectives and Evaluation Items: The following primary, secondary, and exploratory objectives and endpoints will be assessed for this study: Statistical analyses of the primary and key secondary endpoints will be performed.

[0102] [Table 5-1]

[0103] [Table 5-2]

[0104] Study design: This is an open-label, Phase 3 study to evaluate the long-term safety of lebrikizumab in participants aged 6 months to 18 years with moderate to severe AD.

[0105] Participants who complete the KGBI study through week 16 without requiring the use of systemic rescue medications are eligible to enroll in Study KGBJ, which is designed to evaluate the long-term safety of lebrikizumab for moderate-to-severe atopic dermatitis.

[0106] Participants are considered enrolled once all baseline procedures are completed and the investigator determines the participant meets the inclusion and exclusion criteria. The planned treatment duration for each participant is approximately 52 weeks. All participants will enter a post-treatment follow-up period 12 weeks after their last dose of lebrikizumab.

[0107] Table 6 describes the doses and frequency of lebrikizumab used in this clinical study.

[0108] [Table 6]

[0109] Patient Population: Approximately 250 participants will be enrolled to receive lebrikizumab.

[0110] Inclusion Criteria: Participants are eligible for inclusion in the study only if all of the following criteria apply: 1. Received treatment at Study KGBI and successfully completed study treatment and the final Study KGBI visit. 2. For female participants of childbearing potential, use highly effective contraception consistent with local regulations. 3. Willing and able to comply with all clinic visits and study-related procedures and questionnaires. 4. Provide written informed consent.

[0111] Exclusion Criteria: Participants will be excluded from the study if any of the following criteria apply: 1. During participation in Study KGBI, a participant experiences a serious adverse event (SAE) considered to be related to lebrikizumab that, in the opinion of the investigator or medical monitor, may indicate that continued treatment with lebrikizumab may present an unreasonable risk to the participant. * . 2. Develop an adverse event (AE) during participation in Study KGBI that is considered to be related to lebrikizumab and that leads to discontinuation of study treatment, which, in the opinion of the investigator or medical monitor, may indicate that continued treatment with lebrikizumab may present an unreasonable risk to the participant. * . 3. Met protocol-defined criteria for permanent study drug discontinuation in Study KGBI if deemed related to lebrikizumab or led to investigator- or sponsor-initiated withdrawal of the participant from the study (e.g., noncompliance, failure to complete study assessments) * . * Note about Exclusion Criteria 1-3: If Study KGBI is still blinded at the time of rollover to Study KGBJ, conditions considered related to study treatment will be considered related to lebrikizumab. 4. Pregnant or breastfeeding, or planning to become pregnant or breastfeed during the study.

Claims

1. 1. A method of treating moderate to severe atopic dermatitis in a patient in need of treatment, said method comprising administering lebrikizumab to said patient, said patient being between 6 months and 12 years of age and weighing at least 6 kilograms (kg).

2. 1. A method for treating moderate to severe atopic dermatitis, comprising: Selecting patients with moderate to severe atopic dermatitis, aged between 6 months and 12 years, and weighing at least 6 kg; administering lebrikizumab to said patient.

3. 1. A method of treating moderate to severe atopic dermatitis in a patient in need of treatment, said method comprising administering lebrikizumab to said patient, said patient being between 12 and 18 years of age and weighing less than 40 kg.

4. 1. A method for treating moderate to severe atopic dermatitis, comprising: Selecting patients with moderate to severe atopic dermatitis, aged between 12 and 18 years, and weighing less than 40 kg; administering lebrikizumab to said patient.

5. The method of any one of claims 1 to 4, wherein the patient is treated for a treatment period of 16 weeks.

6. 6. The method of any one of claims 1-5, wherein lebrikizumab is administered to the patient at 125 mg at week 0 and 125 mg once every 4 weeks from week 2 through week 14 if the patient has a body weight of less than 6 kg to 15 kg.

7. 6. The method of any one of claims 1-5, wherein lebrikizumab is administered to the patient at 250 mg at week 0 and 250 mg once every 4 weeks from week 2 through week 14 if the patient has a body weight of less than 15 kg to 40 kg.

8. 6. The method of any one of claims 1, 2, or 5, wherein lebrikizumab is administered to the patient at 500 mg at weeks 0 and 2, and 250 mg every two weeks from weeks 4 through 14, if the patient has a body weight of 40 kg or greater.

9. 1. A method for treating moderate to severe atopic dermatitis, comprising: selecting a patient with moderate to severe atopic dermatitis and a body weight of 6 kg to less than 15 kg; administering to the patient lebrikizumab at 125 mg at week 0 and 125 mg every 4 weeks from week 2 through week 14.

10. 1. A method for treating moderate to severe atopic dermatitis, comprising: selecting a patient having moderate to severe atopic dermatitis and weighing less than 15 kg to 40 kg; administering to the patient lebrikizumab at 250 mg at week 0 and 250 mg every 4 weeks from week 2 through week 14.

11. 1. A method for treating moderate to severe atopic dermatitis, comprising: Selecting a patient with moderate to severe atopic dermatitis and weighing 40 kg or more; administering to the patient lebrikizumab at 500 mg at weeks 0 and 2, and 250 mg every two weeks from weeks 4 through 14.

12. The method according to any one of claims 9 to 11, wherein the patient is between 6 months and 12 years old.

13. The method of claim 9 or 10, wherein the patient is between 12 and 18 years old.

14. 14. The method of any one of claims 1-13, wherein the patient has an Eczema Area and Severity Index (EASI) score of 16 or greater, an Investigator Global Assessment (IGA) score of 3 or greater, and more than 10% of the body surface area (BSA) affected by atopic dermatitis prior to administration of lebrikizumab.

15. The method of any one of claims 1-14, wherein the patient had an inadequate response to topical corticosteroids prior to administration of lebrikizumab.

16. The method of any one of claims 1 to 15, wherein the patient has had atopic dermatitis for at least 12 months if aged 6 years or older.

17. 16. The method of any one of claims 1, 2, 5-12, or 14-15, wherein the patient has had atopic dermatitis for at least 6 months if the patient is between 6 months and under 6 years of age.

18. The method of any one of claims 1 to 17, wherein lebrikizumab is administered subcutaneously to the patient.

19. 19. The method of any one of claims 1 to 18, further comprising determining the patient's EASI score at 16 weeks.

20. 20. The method of claim 19, wherein the EASI score determined at week 16 is reduced by 75% or more compared to the EASI score determined prior to administration of lebrikizumab.

21. 20. The method of claim 19, wherein the EASI score determined at week 16 is reduced by 90% or more compared to the EASI score determined prior to administration of lebrikizumab.

22. 22. The method of any one of claims 1 to 21, further comprising determining the IGA score of the patient at week 16.

23. 23. The method of claim 22, wherein the IGA score determined at week 16 is 0 or 1, and wherein the IGA score determined at week 16 is reduced by 2 or more points compared to the IGA score determined prior to administration of lebrikizumab.

24. 24. The method of any one of claims 1 to 23, further comprising determining the patient's Pruritis Numeric Rating Scale (NRS) score at 16 weeks.

25. 25. The method of claim 24, wherein the pruritus NRS score determined at week 16 is reduced by 4 or more points compared to the pruritus NRS score determined prior to administration of lebrikizumab.

26. At week 16, the patients had the following characteristics: i. The percentage of BSA affected by atopic dermatitis; ii. DLQI, cDLQI, and / or IDLQI; iii. PRISM, iv. SCORAD, v. PROMIS anxiety, PROMIS depression, PROMIS sleep disorder, and / or PROMIS sleep-related disorder; vi. POEM, vii. EQ-5D-Y and / or EQ-5D-5L; viii. mSQAAQ, ix. DFI, x. WPAI-AD-CG The method of any one of claims 1 to 25, further comprising determining one or more of:

27. The method of any one of claims 1-26, wherein lebrikizumab is administered to the patient using a subcutaneous administration device.

28. 28. The method of claim 27, wherein the subcutaneous administration device is selected from a pre-filled syringe, a disposable pen injection device, a microneedle device, a microinfuser device, a needle-free injection device, or an autoinjector device.

29. 29. The method of any one of claims 1 to 28, wherein the method further comprises administering one or more topical corticosteroids to the patient.

30. 30. The method of claim 29, wherein the one or more topical corticosteroids is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone.

31. 31. The method of claim 29 or 30, wherein the one or more topical corticosteroids are administered simultaneously with lebrikizumab.

32. Lebrikizumab for use in the treatment of moderate to severe atopic dermatitis in patients aged 6 months to 12 years and weighing at least 6 kg.

33. Lebrikizumab for use in the treatment of moderate to severe atopic dermatitis in patients aged 12 to 18 years and weighing less than 40 kg.

34. 34. The lebrikizumab for use according to claim 32 or 33, wherein the patient is treated for a treatment period of 16 weeks.

35. 35. The lebrikizumab for use according to any one of claims 32 to 34, wherein lebrikizumab is administered to said patient at 125 mg at week 0 and 125 mg once every 4 weeks from week 2 to week 14 if said patient has a body weight of less than 6 kg to 15 kg.

36. 35. The lebrikizumab for use according to any one of claims 32 to 34, wherein lebrikizumab is administered to said patient at 250 mg at week 0 and 250 mg once every 4 weeks from week 2 to week 14 if said patient has a body weight of less than 15 kg to 40 kg.

37. 35. The lebrikizumab for use according to claim 32 or 34, wherein lebrikizumab is administered to said patient at 500 mg at weeks 0 and 2 and at 250 mg once every two weeks from weeks 4 to 14 if said patient has a body weight of 40 kg or greater.

38. 1. Lebrikizumab for use in the treatment of moderate to severe atopic dermatitis in a patient having a body weight of 6 kg to less than 15 kg, wherein lebrikizumab is administered to said patient at 125 mg at week 0 and 125 mg once every 4 weeks from week 2 to week 14.

39. 1. Lebrikizumab for use in the treatment of moderate to severe atopic dermatitis in a patient having a body weight of 15 kg to less than 40 kg, wherein lebrikizumab is administered to said patient at 250 mg at week 0 and 250 mg once every 4 weeks from week 2 to week 14.

40. 1. Lebrikizumab for use in the treatment of moderate to severe atopic dermatitis in a patient weighing 40 kg or more, wherein lebrikizumab is administered to said patient at 500 mg at weeks 0 and 2, and 250 mg once every two weeks from weeks 4 to 14.

41. The lebrikizumab for use according to any one of claims 38 to 40, wherein the patient is between 6 months and 12 years old.

42. 40. The lebrikizumab for use according to claim 38 or 39, wherein the patient is between 12 and 18 years of age.

43. 43. Lebrikizumab for use according to any one of claims 32 to 42, wherein the patient has an Eczema Area and Severity Index (EASI) score of 16 or greater, an Investigator Global Assessment (IGA) score of 3 or greater, and more than 10% of the body surface area (BSA) affected by atopic dermatitis prior to administration of lebrikizumab.

44. 44. The method of claim 32, wherein the patient has had an inadequate response to topical corticosteroids prior to administration of lebrikizumab.

45. 45. The lebrikizumab for use according to any one of claims 32 to 44, wherein the patient, if 6 years of age or older, has had atopic dermatitis for at least 12 months.

46. 45. The lebrikizumab for use according to any one of claims 32, 34-41, or 43-44, wherein the patient has had atopic dermatitis for at least 6 months if the patient is under 6 months of age.

47. The lebrikizumab for use according to any one of claims 32 to 46, wherein the lebrikizumab is administered subcutaneously to the patient.

48. 48. The lebrikizumab for use according to any one of claims 32 to 47, wherein the patient is further administered one or more topical corticosteroids.

49. 49. The lebrikizumab for use according to claim 48, wherein the one or more topical corticosteroids is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone.

50. 50. The method of claim 48 or 49, wherein the one or more topical corticosteroids are administered simultaneously with lebrikizumab.

51. 1. Use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient aged between 6 months and 12 years and weighing at least 6 kg.

52. 1. Use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient aged between 12 and 18 years and weighing less than 40 kg.

53. 1. Use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient having a body weight of 6 kg to less than 15 kg, wherein lebrikizumab is administered to the patient at 125 mg at week 0 and at 125 mg once every 4 weeks from week 2 to week 14.

54. 1. Use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient having a body weight of 15 kg to less than 40 kg, wherein lebrikizumab is administered to the patient at 250 mg at week 0 and at 250 mg once every 4 weeks from week 2 to week 14.

55. 1. Use of lebrikizumab in the manufacture of a medicament for treating moderate to severe atopic dermatitis in a patient weighing 40 kg or greater, wherein lebrikizumab is administered to the patient at 500 mg at weeks 0 and 2, and at 250 mg once every two weeks from weeks 4 to 14.

56. A pharmaceutical composition comprising lebrikizumab for treating moderate to severe atopic dermatitis in a patient aged between 6 months and 12 years and weighing at least 6 kg.

57. A pharmaceutical composition comprising lebrikizumab for treating moderate to severe atopic dermatitis in a patient aged between 12 and 18 years and weighing less than 40 kg.

58. 1. A pharmaceutical composition comprising lebrikizumab for treating moderate to severe atopic dermatitis in a patient weighing 6 kg to less than 15 kg, wherein lebrikizumab is administered to the patient at 125 mg at week 0 and at 125 mg once every 4 weeks from week 2 through week 14.

59. 1. A pharmaceutical composition comprising lebrikizumab for treating moderate to severe atopic dermatitis in a patient having a body weight of 15 kg to less than 40 kg, wherein lebrikizumab is administered to said patient at 250 mg at week 0 and at 250 mg once every 4 weeks from week 2 through week 14.

60. 1. A pharmaceutical composition comprising lebrikizumab for treating moderate to severe atopic dermatitis in a patient weighing 40 kg or more, wherein lebrikizumab is administered to the patient at 500 mg at weeks 0 and 2, and at 250 mg once every two weeks from weeks 4 to 14.

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