Peptide administration regimen for chronic inflammatory demyelinating polyneuropathy

Abstract

The present invention relates to a peptide administration regimen for chronic inflammatory demyelinating polyneuropathy (CIDP), and specifically, to a regimen for administering a peptide, comprising an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof, for treating chronic inflammatory demyelinating polyneuropathy.

Description

Peptide therapy for chronic inflammatory demyelinating polyneuropathy

[0001] The present invention relates to a peptide administration therapy for chronic inflammatory demyelinating polyneuropathy (CIDP).

[0002] Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is an autoimmune neurological disorder characterized by demyelination of peripheral nerves, leading to progressive or relapsing motor and sensory decline. It resembles Guillain-Barré Syndrome, but has a more chronic course, with symptoms worsening over several months or alternating between relapses and remissions.

[0003] CIDP is caused by a complex immunological mechanism involving T cells, B cells, macrophages, and autoantibodies, leading to demyelination and peripheral nerve axonal damage. Therefore, corticosteroids, intravenous immunoglobulin (IVIg), and plasmapheresis are currently the standard clinical treatments.

[0004] Among these, corticosteroids are widely used as first-line immunosuppressants and can be effective in temporarily alleviating symptoms. However, their clinical limitations lie in the high risk of serious systemic side effects with long-term administration. Common steroid-related side effects include osteoporosis, weight gain, hyperglycemia, increased risk of infection, hypertension, gastrointestinal disorders, mood disorders, insomnia, and adrenal suppression. These risks are particularly pronounced in patients with chronic CIDP, where long-term administration is often unavoidable. Furthermore, some patients frequently experience clinical problems, such as limited response to steroid treatment or rapid relapse upon discontinuation of treatment.

[0005] Therefore, there is a need for new treatment strategies or agents that can effectively control the disease while avoiding the side effects of steroids.

[0006] Accordingly, the inventors of the present invention have made efforts to develop a therapeutic agent and a dosing regimen thereof that have an effective therapeutic effect while minimizing side effects as a therapeutic agent, and as a result, have completed the present invention by confirming that a safe and excellent effect can be obtained in the treatment of CIDP by intravenously administering an injectable preparation containing the peptide of the present invention to CIDP patients.

[0007] [Prior Art Literature]

[0008] [Non-patent literature]

[0009] Dalakas MC,Advances in the diagnosis, pathogenesis and treatment of CIDP. Nat Rev Neurol. 2011 Aug 16;7(9):507-17.

[0010] K. Kuitwaard et al.,Randomized trial of intravenous immunoglobulin maintenance treatment regimens in chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol. 2021 Jan;28(1):286-296.

[0011] Rostasy KM et al., Progressive muscle weakness after high-dose steroids in two children with CIDP. Pediatric Neurology 2003;29(3):236-238.

[0012] The purpose of the present invention is to provide a peptide administration regimen having an effective therapeutic effect on chronic inflammatory demyelinating polyneuropathy (CIDP) while minimizing side effects.

[0013] In order to achieve the object of the present invention, the present invention provides a pharmaceutical composition for treating chronic inflammatory demyelinating polyneuropathy (CIDP), comprising a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof, wherein the peptide or the pharmaceutically acceptable salt thereof is administered intravenously.

[0014] In addition, the present invention provides a method for treating chronic inflammatory demyelinating polyneuropathy (CIDP), comprising a step of intravenously administering to a subject a pharmaceutical composition comprising a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof.

[0015] In addition, the present invention provides a use for a pharmaceutical composition for treating chronic inflammatory demyelinating polyneuropathy (CIDP), wherein the pharmaceutical composition comprises a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof, and the peptide or the pharmaceutically acceptable salt thereof is administered intravenously.

[0016] In addition, the present invention provides a use for preparing a pharmaceutical composition for treating chronic inflammatory demyelinating polyneuropathy (CIDP), wherein the pharmaceutical composition comprises a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof, and the peptide or the pharmaceutically acceptable salt thereof is administered intravenously.

[0017] According to the present invention, a safe and excellent effect can be obtained in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) by intravenously administering an injectable preparation containing the peptide of the present invention to a patient with CIDP.

[0018] Figure 1 is a diagram showing a clinical trial flow chart of a peptide according to one embodiment of the present invention for patients with chronic inflammatory demyelinating polyneuropathy (CIDP).

[0019] Figure 2 is a schematic diagram showing a dose escalation diagram of a peptide according to one embodiment of the present invention for CIDP patients.

[0020] FIG. 3 is a diagram showing the change in the INCAT (Inflammatory Neuropathy Cause and Treatment) disability score compared to baseline at a certain time point after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0021] FIG. 4 is a diagram confirming the clinical response to the change in INCAT disability score at a certain point in time after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0022] FIG. 5 is a diagram showing the change in the Medical Research Council (MRC) total score at a certain time point after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0023] FIG. 6 is a diagram showing the change in the percentile score of I-RODS (Inflammatory Rasch-Built Overall Disability Scale) at a certain time point after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0024] FIG. 7 is a diagram showing the change in the Timed Up-and-Go (TUG) score at a certain time point after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0025] Figure 8 is a diagram showing the change in mean grip strength at a certain point in time after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0026] FIG. 9 is a diagram showing the change in the ONLS (Overall Neuropathy Limitations Scale) score at a certain time point after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0027] FIG. 10 is a diagram showing the average blood concentration-time pattern of a drug after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0028] Figure 11 is a diagram showing changes in immunophenotype at a certain time point after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0029] Figure 12 is a diagram showing changes in serum IL-6 and TGF-β at a certain point after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0030] Figure 13 is a diagram showing changes in serum C4 complement at a certain point in time after intravenous administration of 120 mg (cohort 1), 240 mg (cohort 2), or 360 mg (cohort 3) of a peptide according to one embodiment of the present invention to CIDP patients.

[0031] The present invention is described in detail below.

[0032] The present invention provides a pharmaceutical composition for treating chronic inflammatory demyelinating polyneuropathy (CIDP), comprising a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof, wherein the peptide or the pharmaceutically acceptable salt thereof is administered intravenously.

[0033] In addition, the present invention provides a method for treating chronic inflammatory demyelinating polyneuropathy (CIDP), comprising a step of intravenously administering to a subject a pharmaceutical composition comprising a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof.

[0034] In addition, the present invention provides a use for a pharmaceutical composition for treating chronic inflammatory demyelinating polyneuropathy (CIDP), wherein the pharmaceutical composition comprises a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof, and the peptide or the pharmaceutically acceptable salt thereof is administered intravenously.

[0035] In addition, the present invention provides a use for preparing a pharmaceutical composition for treating chronic inflammatory demyelinating polyneuropathy (CIDP), wherein the pharmaceutical composition comprises a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof, and the peptide or the pharmaceutically acceptable salt thereof is administered intravenously.

[0036] In the present invention, the “peptide” refers to a polymer composed of two or more amino acids linked by amide bonds (or peptide bonds).

[0037] The peptide of the present invention may be composed of an amino acid represented by SEQ ID NO: 1, and may include an amino acid sequence having a sequence identity of 75% or more, preferably 80% or more, more preferably 90% or more, and most preferably 95% or more, with the amino acid sequence represented by SEQ ID NO: 1. More specifically, the peptide of the present invention may include an amino acid sequence having a sequence identity of 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more with the amino acid sequence represented by SEQ ID NO: 1.

[0038] Additionally, the peptide of the present invention may additionally include a targeting sequence, a tag, a labeled residue, an amino acid sequence manufactured for a specific purpose to increase half-life or peptide stability.

[0039] Additionally, the peptide of the present invention can be obtained using various methods widely known in the art. For example, it can be produced using polynucleotide recombination and protein expression systems, in vitro synthesis through chemical synthesis such as peptide synthesis, and cell-free protein synthesis methods.

[0040] Additionally, a protecting group may be attached to the N- or C-terminus of the peptide to obtain better chemical stability, enhanced pharmacological properties (e.g., half-life, absorbability, potency, efficacy, etc.), altered specificity (e.g., broadened biological activity spectrum), or reduced antigenicity. Examples of protecting groups include, but are not limited to, an acetyl group, a fluorenyl methoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol (PEG).

[0041] Additionally, the peptide of the present invention may be in a pharmaceutically acceptable salt form, specifically, but not limited to, an acetate salt.

[0042] In the present invention, the peptide or a pharmaceutically acceptable salt thereof can be administered intravenously in a dosage of 120 mg to 360 mg, and specifically, can be administered intravenously once or multiple times in a dosage of 120 mg to 360 mg.

[0043] Additionally, the composition can be administered intravenously to a subject having CIDP, specifically to a subject having CIDP refractory to corticosteroid treatment, more specifically to a subject having CIDP refractory to corticosteroid treatment, single or multiple intravenous administrations, and even more specifically to a subject having CIDP refractory to corticosteroid treatment, single or multiple intravenous administrations in a dosage of 120 mg to 360 mg.

[0044] Examples of the above corticosteroids include, but are not limited to, prednisone, prednisolone, dexamethasone, methylprednisolone, triamcinolone, betamethasone, and hydrocortisone.

[0045] The above CIDP can be diagnosed according to the 2021 revised guidelines jointly established by the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) (Van den Bergh et al., European Academy of Neurology / Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision. Eur J Neurol. 2021 Nov;28(11):3556-3583).

[0046] CIDP is clinically characterized by progressive, symmetrical muscle weakness in the proximal and distal extremities. This weakness can be observed in both the lower and upper extremities, and is typically bilateral and non-symmetrical. It is also accompanied by sensory abnormalities (e.g., numbness, pain, decreased vibration, or position sense) and decreased or absent deep tendon reflexes, which must persist for at least 8 weeks. Clinical findings are crucial for the suspicion and screening of the disorder prior to electrophysiological evaluation, and the following features are particularly diagnostic: (i) central muscle weakness in the lower extremities that interferes with activities of daily living, (ii) fine motor deficits in the upper extremities (e.g., difficulty buttoning or using chopsticks), (iii) instability during gait, (iv) bilateral loss of ankle reflexes, and (v) sensory ataxia.

[0047] Furthermore, although electrophysiological criteria are required for the confirmation of diagnosis, if clinically typical CIDP findings are observed, it can be used as a primary basis for diagnosis, and if electrophysiological findings are insufficient, the possibility of diagnosis can be strengthened through cerebrospinal fluid examination, neuroimaging MRI, tissue biopsy, and treatment response.

[0048] Furthermore, CIDP requires differential diagnosis from various other conditions. Diabetic polyneuropathy, hereditary neuropathy (Charcot-Marie-Tooth disease), myasthenia gravis, myositis, spinal cord lesions, vasculitic neuropathy, infectious or toxic neuropathy, and malignant tumor-related neuropathy may present with similar clinical features and should be ruled out.

[0049] The subject may be assessed for one or more indicators that determine specific signs, symptoms, dysfunctions, or biomarkers associated with CIDP and that can be qualitatively or quantitatively assessed. Exemplary assessment indicators include, but are not limited to: the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score to assess the degree of impairment in upper and lower extremity function; the Medical Research Council (MRC) total score to quantify the level of whole body muscle strength; the Inflammatory Rasch-Built Overall Disability Scale (I-RODS), a patient-centered assessment tool for daily function; the Timed Up-and-Go (TUG) to assess lower extremity function and mobility; the Mean Grip Strength (MGR) as an indicator of hand function and grip strength recovery; and the Overall Neuropathy Limitations Scale (ONLS) to assess the degree of limitations in activities of daily living in the upper and lower extremities, respectively. The above indicators are discussed elsewhere herein, for example, in Example <2-7>.

[0050] In the present invention, the subject can have improved upper and / or lower limb dysfunction, improved muscle function, and recovered grip strength by administering the composition of the present invention, specifically intravenously, and more specifically single or multiple intravenous administrations, and the improvement can be confirmed through evaluation of the following indicators.

[0051] Specifically, the subject is improved in one or more of the following indices by administration of the composition of the present invention: 1) INCAT disability score; 2) MRC total score; 3) I-RODS; 4) TUG; 5) average grip strength; and 6) ONLS.

[0052] In the above subject, at least one of the above indicators is determined after administration of the composition of the present invention, for example, on the 14th or 28th day.

[0053] More specifically, the INCAT disability score of the subject is determined after administration of the composition of the present invention, for example, on day 14 or day 28. The INCAT disability score of the subject determined after administration, for example, on day 14 or day 28, is reduced by at least 1 point compared to the INCAT disability score determined before administration of the composition of the present invention (baseline).

[0054] Additionally, the MRC total score of the subject is determined after administration of the composition of the present invention, for example, on day 14 or day 28. The MRC total score of the subject determined after administration, for example, on day 14 or day 28, increases by 2 or more points compared to the MRC total score (baseline) determined before administration of the composition of the present invention.

[0055] Additionally, the I-RODS percentile score of the subject is determined after administration of the composition of the present invention, for example, on day 14 or day 28. The I-RODS percentile score of the subject determined after administration, for example, on day 14 or day 28, is converted to a percentile score basis and increases by 4 or more points compared to the baseline.

[0056] Additionally, the TUG of the subject is determined after administration of the composition of the present invention, for example, on day 14 or day 28. After administration, the TUG of the subject determined after administration, for example, on day 14 or day 28, is reduced by at least 4 seconds compared to the TUG (baseline) determined before administration of the composition of the present invention.

[0057] Additionally, the average grip strength of the subject is determined after administration of the composition of the present invention, for example, on day 14 or day 28. After administration, the average grip strength of the subject determined after administration, for example, on day 14 or day 28, increases by at least 8 kPa compared to the average grip strength (baseline) determined before administration of the composition of the present invention.

[0058] Additionally, the ONLS score of the subject is determined after administration of the composition of the present invention, for example, on day 14 or day 28. The ONLS score of the subject determined after administration, for example, on day 14 or day 28, is reduced by at least 1 point compared to the ONLS score determined before administration of the composition of the present invention (baseline).

[0059] In addition, improvement may be observed for more than 4 weeks in the subject by administering the composition of the present invention, specifically by intravenous administration, and more specifically by single or multiple intravenous administrations.

[0060] In addition, CIDP can be treated by inducing activation of regulatory T cells, secretion of anti-inflammatory cytokines (e.g., TGF-β), and / or suppression of inflammatory cytokines (e.g., IL-6) by administering the composition of the present invention to the subject.

[0061] In the present invention, the composition can be formulated as an injection.

[0062] The above injection may contain a buffer; a pH adjusting agent; an isotonic agent; and a surfactant.

[0063] Specifically, the buffer may be included to maintain a stable pH and improve the structural stability of the peptide. The buffer serves to maintain a constant pH in response to slight acidity changes within the formulation, and contributes to ensuring the storage stability and in vivo safety of the formulation. Examples of buffers may include sodium monohydrogen phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate monohydrate, phosphate buffers, histidine / histidine hydrochloride buffers, sodium citrate / citric acid buffers, and any other pharmaceutically acceptable buffer known in the art, and mixtures of these buffers may also be used.

[0064] The pH regulator is used to adjust the pH of the formulation to the target range, and unlike a buffer, it plays a role in securing an initial set value rather than continuously maintaining the pH. Examples of pH regulators that can be used include sodium hydroxide (NaOH), hydrochloric acid (HCl), tromethamine (Tris), lactic acid, acetic acid, citric acid, etc., and one or more of these may be used, but are not limited thereto. In particular, tromethamine can function as both a pH regulator and a buffer. The pH regulator can be selected in an appropriate concentration and type considering the stability of the formulation, inhibition of peptide degradation, biocompatibility, and whether or not it is irritating upon injection, and can be added in stages for precise adjustment within the pH range, if necessary. The injection according to the present invention can be adjusted to a pH of, but is not limited to, 5.0 to 7.0, 5.5 to 6.5, 5.7 to 6.3, or 6.0.

[0065] The above isotonic agent plays a role in maintaining an appropriate osmotic pressure when administering the peptide in the body, and also exhibits the effect of further stabilizing the peptide in the formulation. Examples of the isotonic agent include sugar alcohols, water-soluble inorganic salts, amino acids, etc., and specifically, sodium chloride, which is a water-soluble inorganic salt, can be mentioned. In addition, the isotonic agent may be contained at 0.1 to 2 w / v%, 0.1 to 1.5 w / v%, 0.1 to 1 w / v%, 0.3 to 1 w / v%, 0.5 to 1 w / v%, 0.6 to 0.9 w / v%, or 0.7 to 0.9 w / v% with respect to the total injection.

[0066] The surfactant lowers the surface tension of the protein solution, thereby preventing the protein from adsorbing or aggregating on the hydrophobic surface. Examples of the surfactant include polysorbate 20 or polysorbate 80. In addition, the surfactant may be contained in an amount of 0.001 to 0.1 w / v%, 0.005 to 0.1 w / v%, 0.005 to 0.05 w / v%, 0.007 to 0.03 w / v%, 0.008 to 0.03 w / v%, or 0.009 to 0.015 w / v% based on the total injection.

[0067] Additionally, the injectable formulation may further include one or more additives to enhance the physical and chemical stability of the formulation or improve biocompatibility. Such additives include, but are not limited to, stabilizers, wetting agents, emulsifiers, solubilizers, solvents, osmotic pressure regulators, buffers, preservatives, antioxidants, and lyophilization aids.

[0068] Hereinafter, the present invention will be described in detail by examples.

[0069] However, the following examples are only illustrative of the present invention, and the content of the present invention is not limited to the following examples.

[0070] <Example 1> Preparation of test drug

[0071] Using PSP fragments (PSP monomers), trimer-type polymers were prepared as shown in Table 1 below. Subsequently, the synthesized peptides were purified using high-performance liquid chromatography (SHIMADZU Prominence HPLC), and the column used was Shiseido capcell pak C18 Column (4.6 × 50 mm). In addition, the mass of the synthesized peptides was confirmed using a mass spectrometer (AXIMA Assurance, MALDI-TOF, Shimadzu).

[0072] Amino acid sequence molecular weight (MW) peptide (KINE-101) PSPPSPPSP (SEQ ID NO: 1) 861.9 g / mol

[0073] Next, an injectable formulation (KINE-101 strain) containing the acetate salt of the synthesized peptide was prepared as shown in Table 2 below.

[0074] KINE-101Main ingredient and dosage formColorless to slightly colored transparent liquid in a colorless transparent vialIngredients and dosage (per 1 mL)Main ingredient: KINE-101 acetate 12.5 mg / mLExcipientsSodium phosphate dibasic monohydrate (USP) 1.38 mg / mLSodium hydroxide (NF) appropriate amountSodium chloride (USP) 8.00 mg / mLPolysorbate 20 (NF) 0.10 mg / mLWater for Injection (USP) appropriate amountStorage methodAirtight container, store frozen (-20±5℃)Use (expiration) periodUp to 36 months from the date of manufacture

[0075] <Example 2> Clinical trial

[0076] A multicenter, open-label, single-dose, stepwise escalation, phase 1 clinical trial was conducted to determine the safety and tolerability of KINE-101 manufactured in <Example 1> in subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) refractory to corticosteroid treatment.

[0077] <2-1> Purpose of clinical trial

[0078] 1) Primary objective: To evaluate the safety and tolerability of a single intravenous dose of KINE-101 in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) refractory to corticosteroid treatment.

[0079] 2) Exploratory objective: To evaluate the efficacy, pharmacokinetics, and pharmacodynamics of KINE-101 after a single intravenous dose in patients with CIDP refractory to corticosteroid treatment.

[0080] <2-2> Number of clinical trial subjects

[0081] It was divided into three cohorts (9 to 18 people), with 3 to 6 people in each cohort.

[0082] <2-3> Criteria for selecting clinical trial subjects

[0083] Clinical trial subjects were selected based on the following selection criteria:

[0084] 1) Adults aged 19 years or older as of the date of consent

[0085] 2) Patients with CIDP who have not responded to corticosteroid treatment for at least 3 months prior to clinical trial registration, or those who cannot be administered or continue to receive corticosteroids for safety reasons.

[0086] 3) Typical CIDP clinical criteria according to the 2021 guidelines of the European Academy of Neurology / Peripheral Nerve Society (EAN / PNS) as CIDP at screening * Those who meet the requirements

[0087] * All of the following criteria must be met:

[0088] - Progressive or recurrent, symmetrical, muscle weakness in the arms and legs, sensory involvement in at least two limbs

[0089] - Symptoms occur and persist for at least 8 weeks

[0090] - Absence or reduction of tendon reflexes in all limbs

[0091] 4) Those with an Inflammatory Neuropathy Cause and Treatment (INCAT) disability score of 2 or more at the time of screening (the 2 points must be entirely due to leg disability).

[0092] 5) Those with a CIDP Disease Activity Status (CDAS) of 3 or higher at the time of screening

[0093] 6) Those who received IVIg at least 2 months prior to administration of clinical trial drugs

[0094] 7) Women of childbearing age ** Or, for men, you or your partner must use highly effective contraception for at least 28 days after taking the investigational drug. *** Those who agree to use

[0095] *** Highly effective contraception:

[0096] Subjects must use at least one of the contraceptive methods below.

[0097] 1) Hormonal contraceptives (oral, vaginal, transdermal, injectable, subcutaneous implants)

[0098] 2) Intrauterine device (IUD, IUS)

[0099] 3) Vasectomy for men, tubal ligation for women of childbearing age

[0100] 4) Absolute Abstinence: If the investigator determines that the subject's age, occupation, lifestyle, or sexual orientation warrants contraception, complete abstinence from sexual intercourse is acceptable. However, periodic abstinence (such as the menstrual cycle method, mucus method, or symptomatic thermographic method), abstinence, or withdrawal are not recognized as appropriate contraceptive methods.

[0101] ** Women of childbearing potential: Women who have experienced menarche and have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or have not been postmenopausal for more than 1 year.

[0102] 8) Those with sufficient venous access to allow drug administration by injection and blood sample collection according to the clinical trial plan.

[0103] 9) Those who are willing to voluntarily participate in the clinical trial and comply with all trial procedures.

[0104] Additionally, subjects who met the following criteria were excluded from the clinical trial:

[0105] 1) Patients with polyneuropathy of other causes, including:

[0106] Multifocal motor neuropathy (MMN); monoclonal gammopathy of uncertain significance with anti-myelin associated glycoprotein immunoglobulin M (IgM) antibodies; hereditary demyelinating neuropathies; polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin change syndromes; lumbosacral plexus neuropathy; polyneuropathy most likely due to diabetes; polyneuropathy most likely due to systemic disease; drug- or toxin-induced polyneuropathy

[0107] 2) Those with a history of myelopathy or confirmed central demyelination

[0108] 3) If you have a known allergy or hypersensitivity to the clinical trial drug or its excipients.

[0109] 4) Those who are judged by the investigator to be unsuitable for clinical trial participation due to reasons such as uncontrolled severe liver disease, central nervous system disease, alcoholism, drug abuse, or mental illness.

[0110] 5) Patients with any other disease that better explains the patient's signs and symptoms, such as significant persistent neurological deficit due to stroke or trauma to the central nervous system (CNS), or peripheral neuropathy due to another cause, such as connective tissue disease or systemic lupus erythematosus.

[0111] 6) Those with a history of malignant tumor within 5 years prior to screening (excluding appropriately treated squamous cell and basal cell carcinoma of the skin, cervical intraepithelial carcinoma, localized prostate cancer, or malignant tumors that have been cured or are judged to have a minimal risk of recurrence within 1 year of screening in the investigator's opinion)

[0112] 7) Those with a history of moderate or severe heart failure or a history of severe cardiovascular disease (e.g., myocardial infarction or ischemic stroke)

[0113] 8) Those with a history of moderate or severe substance or alcohol use disorder within 1 year prior to screening

[0114] 9) Those whose serum pregnancy test result is positive at the time of screening

[0115] 10) Those who plan to donate eggs or sperm, breastfeed, or become pregnant for at least 28 days after administration of clinical trial drugs.

[0116] 11) Those who have been administered systemic immunosuppressants or stimulants (e.g., IFN-γ, IL-2, IL-12, etc.) within 5 times the half-life before administration of the investigational drug (e.g., Pembrolizumab half-life 25 days → at least 18 weeks, Ustekinumab half-life 22 days → at least 16 weeks)

[0117] 12) Those who received plasma exchange treatment within 8 weeks prior to administration of clinical trial drugs

[0118] 13) Those with chronic infections (e.g., bronchiectasis, chronic osteomyelitis, chronic pyelonephritis) or those requiring chronic anti-infective treatment (e.g., antiviral drugs)

[0119] 14) Patients expected to require corticosteroid administration during the clinical trial period. However, topical and inhaled medications are permitted.

[0120] 15) Patients with active hepatitis B or active hepatitis C

[0121] 16) A history of positive human immunodeficiency virus (HIV)1 or HIV2 antibodies, or a positive HIV test result during screening

[0122] 17) Those who show any of the following results in laboratory tests at the time of screening:

[0123] - AST (sGOT) or ALT (sGPT) > 3 times the upper limit of normal range

[0124] - Hb < 9.0g / dL

[0125] - Absolute Neutrophil Count < 1500μl

[0126] - Platelet count < 100×10 3 / μl

[0127] 18) Subjects who have undergone major surgery (e.g., requiring general anesthesia [although not all procedures requiring general anesthesia are necessarily major surgery]) within the 3 months prior to screening, have not fully recovered from the surgery, or have surgery planned during the period in which the subject is expected to participate in the study.

[0128] 19) A person who is judged by the investigator to be unsuitable for clinical trial participation due to other reasons including laboratory test results.

[0129] <2-4> Clinical trial administration method

[0130] As shown in the clinical trial flow chart in Fig. 1, the test drug (KINE-101 120 mg, 240 mg, 360 mg) was administered intravenously as a single dose to Cohort 1 (KINE-101 120 mg), Cohort 2 (KINE-101 240 mg), and Cohort 3 (KINE-101 360 mg) on ​​Visit 2 (Day 1). The KINE-101 extract was prepared into 40 mL according to the dose group and administered intravenously using a syringe pump. The administration method was set to 1 mL / min of the syringe pump infusion speed, and the total infusion volume was 30 mL, and the injection was administered over 30 minutes.

[0131] Specifically, after obtaining consent to participate in the clinical trial, subjects who were finally determined to be eligible for the screening test (≤ 28 days) and met the inclusion / exclusion criteria participated in the clinical trial. Subjects who failed the screening test could be rescreened after discussion between the investigator and sponsor. Rescreened subjects were assigned a new screening number. Subjects were admitted to the hospital the day before Visit 2 (Day 1) to undergo related procedures and were discharged on Visit 4 (Day 3), 48 hours after administration of the study drug. All procedures were performed before discharge. Subjects received a single intravenous dose of the study drug at the planned dose on Visit 2 (Day 1). Safety evaluations (adverse events, laboratory tests, vital signs, physical examinations, and electrocardiograms), including the occurrence of DLTs, as well as efficacy and pharmacokinetic / pharmacodynamic evaluations were performed according to the planned clinical trial schedule up to 14 days after administration of the study drug. Dose escalation was based on a 3+3 design as shown in Figure 2 and review of the previous cohort results. The planned dose groups for KINE-101 were Cohort 1 (120 mg), Cohort 2 (240 mg), and Cohort 3 (360 mg). Once safety and tolerability were confirmed in the previous cohort, the dose was sequentially increased to the next cohort.

[0132] The above 3+3 design was as follows:

[0133] 1. If no DLT occurred in the first 3 subjects enrolled: Increase dose to the next dose group

[0134] 2. If DLT occurs in 1 out of 3 subjects (1 / 3): Enroll 3 additional subjects in the same dose group and evaluate DLT.

[0135] 1) If DLT occurred in 1 out of 6 patients (1 / 3 + 0 / 3; 1 / 6): Increase dose to the next dose group

[0136] 2) If DLT occurred in 2 or more out of 6 subjects (≥2 / 6): Dose escalation was stopped and the dose was defined as unacceptable.

[0137] 3. MTD: Defined as the highest dose at which less than 33% of clinical trial subjects experience DLT.

[0138] <2-5> DLT Evaluation Criteria and Methods

[0139] DLT is defined as a clinically significant event of CTCAE Grade 3 or higher based on the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) Ver. 5.0, and is a result of a definite or reasonably certain causal relationship with the study drug.

[0140] If a subject discontinued the clinical trial for reasons other than DLT within the observation period (up to 14 days after administration), the subject was excluded from the DLT evaluation and a replacement subject was recruited.

[0141] <2-6> Evaluation variables

[0142] Subjects underwent safety evaluation (adverse events, laboratory tests, vital signs, physical examination, electrocardiogram test) and efficacy and pharmacokinetic / pharmacodynamic evaluation according to the planned clinical trial schedule as shown in Table 3 below.

[0143] VisitScreeningTreatmentFollow-upBaselineVisit 1Visit 2Visit 3Visit 4Visit 5Visit 6Day-Day 28~Day 1Day 2Day 3Day 14Day 28±Visit WindowNANANANA±2±2Subject consentXDemographic information 1) XINCAT / CDAS score X military force 2) X-ray prior / concurrent medication 3) XXXXXXSelection / Exclusion CriteriaXPhysical Examination 4) XXXXXXVital Signs 5) XXXXXX electrocardiogram test6) XXXXXX Laboratory Performance Test 7) XXXXXX Pregnancy Test 8) XX Assignment X Administration of clinical trial drugs 9) XEffectiveness assessmentXXXPharmacokinetics Blood collection 10) X Pharmacodynamics Blood Collection 11) XXXXAbnormal Case 12) XXXXX hospitalization 13)XDischargeX1) Demographic information, including the subject's initials, sex, age (date of birth), smoking history, drinking history, and past drug addiction history, was collected at Visit 1 (Screening). 2) Medical history was investigated for medical history within 6 months prior to Visit 1 (Screening) and for current diseases, including diagnosis, date of diagnosis (year and month of diagnosis), and current status. However, for malignant tumors, medical history within 5 years and for moderate or severe substance or alcohol use disorder, medical history within 1 year were investigated. 3) Prior / concomitant medications were collected at every visit from medications used within 4 weeks prior to Visit 1 (Screening) until the end of the clinical trial. 4) Physical examinations included information on height, weight, head / neck, chest / lungs, heart, abdomen, urinary / reproductive system, limbs, musculoskeletal system, lymph nodes, skin, and other body organs. Physical examinations were performed at Visit 1 (Screening), Visit 2 (Day 1 / just before dosing), Visit 3 (Day 2 / 24 hours after starting dosing), Visit 4 (Day 3 / 48 hours after starting dosing), Visit 5 (Day 14), and Visit 6 (Day 28). Height and weight were measured only at Visit 1 (Screening). 5) Vital signs included systolic / diastolic blood pressure, pulse, body temperature, and respiratory rate at Visit 1 (Screening), Visit 2 (Day 1 / just before dosing, 30 minutes / 1 hour / 2 hours / 6 hours / 12 hours after starting dosing), Visit 3 (Day 2 / 24 hours after starting dosing), Visit 4 (Day 3 / 48 hours after starting dosing), Visit 5 (Day 14), and Visit 6 (Day 28). Blood pressure and pulse were measured in a sitting position after resting for at least 5 minutes.6) Electrocardiograms were performed using the standard 12-lead electrocardiogram method at Visit 1 (Screening), Visit 2 (Day 1 / up to 2 hours before starting dosing, up to 2 hours after starting dosing), Visit 3 (Day 2 / 24 hours after starting dosing), Visit 4 (Day 3 / 48 hours after starting dosing), Visit 5 (Day 14), and Visit 6 (Day 28). However, if test results obtained within 7 days prior to Visit 1 (Screening) were available, they could be substituted for the screening test results. However, if there were clinically significant abnormalities (Clinically Significant, CS) results, a screening test was performed. 7) Laboratory tests were performed at Visit 1 (Screening), Visit 2 (Day 1 / immediately before dosing), Visit 3 (Day 2 / 24 hours after starting dosing), Visit 4 (Day 3 / 48 hours after starting dosing), Visit 5 (Day 14), and Visit 6 (Day 28), and were performed after fasting for at least 8 hours, if possible. If test results obtained within 7 days prior to Visit 1 (Screening) were available, those results could be substituted for the screening test results; however, if a clinically significant abnormal (CS) result was found, the screening test was performed. 8) For women of childbearing potential only, pregnancy was confirmed by serum test at Visit 1 (Screening) and Visit 6 (Day 28, EOS). At other visits, pregnancy was confirmed by urine test if necessary at the investigator's discretion. If the urine test result was positive, pregnancy was confirmed by serum test. 9) The investigational drug was administered intravenously at Visit 2 (Day 1) according to the assigned dose group. 10) Pharmacokinetic (PK) blood collection was performed on Visit 2 (Day 1). 11) Pharmacodynamic (PD) blood collection was performed on Visit 2 (Day 1), Visit 4 (Day 3), Visit 5 (Day 14), and Visit 6 (Day 28).12) Adverse events were collected from Visit 2 (Day 1), the day of administration of the clinical trial drug. 13) The subject was admitted the day before Visit 2 (Day 1) to perform the procedures related to Visit 2 (Day 1), Visit 3 (Day 2), and Visit 4 (Day 3). The subject was discharged on Visit 4 (Day 3), 48 hours after administration of the clinical trial drug, and all procedures were performed prior to discharge.

[0144] Here, the primary endpoints (safety assessment) are as follows: adverse events, laboratory tests, vital signs, physical examinations, and electrocardiograms. Here, the exploratory endpoints are as follows:

[0145] 1. Validity evaluation variables

[0146] 1) Change in INCAT (Inflammatory Neuropathy Cause and Treatment) disability score from baseline

[0147] 2) Change in Medical Research Council (MRC) total score from baseline

[0148] 3) Changes in I-RODS (Inflammatory Rasch-Built Overall Disability Scale) from baseline

[0149] 4) Change in TUG (Timed Up-and-Go) score from baseline

[0150] 5) Change in mean grip strength from baseline

[0151] 6) Change in ONLS (Overall Neuropathy Limitations Scale) from baseline

[0152] 2. Pharmacokinetic endpoints: C max , AUC last , AUC inf , CL, t 1 / 2

[0153] 3. Pharmacodynamic evaluation variables

[0154] 1) Immunophenotyping: CD4, CD25, FoxP3, CD39, CD69, CTLA4, LAG-3, TNFR2, TIGIT, CCR5, CXCR3

[0155] * We analyzed the characteristics of T cell subsets initially gated by CD4.

[0156] 2) Serum analysis: IgM, IgG, IL-2, IL-6, IL-10, IL-17, IFN-γ, MCP-1 (monocyte chemoattractant protein-1), TGF-β

[0157] 3) Serum analysis 2: ANA (Antinuclear Antibodies), Anti-SM (smooth muscle) antibody, Anti-RNP (Ribonucleoprotein) antibody, Anti-SSA (Sjogren syndrome A) antibody, Anti-ds DNA antibody, C4 complement

[0158] 4) Other analyses ** : Anemia, Leukopenia, ESR (Erythrocyte Sedimentation Rate), CRP (C-reactive protein)

[0159] ** Laboratory tests were performed at each visit to check for anemia and leukopenia, and changes in ESR and CRP were observed.

[0160] <2-7> Analysis method

[0161] The analysis groups for each evaluation were as follows:

[0162] 1. Safety analysis group: The safety analysis targeted all subjects who received the clinical trial drug.

[0163] 2. Exploratory evaluation analysis group

[0164] 1) Validity analysis group: Validity analysis was conducted on subjects in the safety analysis group who had at least one validity evaluation result excluding the baseline.

[0165] 2) Pharmacokinetic analysis group: The pharmacokinetic analysis group included subjects who had been administered clinical trial drugs and had pharmacokinetic blood collection and pharmacokinetic evaluation results available for analysis.

[0166] 3) Pharmacodynamic analysis group: The pharmacodynamic analysis group included subjects who were administered clinical trial drugs and had analyzable pharmacodynamic evaluation results.

[0167] The analysis method for each evaluation was as follows:

[0168] 1. Safety Analysis

[0169] The safety analysis was conducted on the safety analysis group and was based on adverse events, laboratory tests, vital signs, physical examinations, and electrocardiograms.

[0170] Specifically, all adverse events occurring after administration of the investigational drug were coded and organized using the latest version of the Medical Dictionary for Regulatory Activities (MedDRA). The number and proportion of subjects experiencing adverse events in each dose group were identified. All adverse events were summarized by severity and relevance to the investigational drug.

[0171] The results of hematology and blood chemistry tests, vital signs, etc. were presented in a list of changes from baseline for each visit, and clinical significance (Not Clinically Significant, NCS / Clinically Significant, CS) was also presented in a list.

[0172] For physical examinations, laboratory tests, and electrocardiograms, the results were categorized as normal / abnormal (or normal / clinically insignificant abnormal / clinically significant abnormal) and presented in a list.

[0173] Additionally, a list was provided of subjects who were normal or clinically insignificantly abnormal before administration but changed to clinically significant abnormalities after administration.

[0174] 2. Validity Analysis

[0175] The efficacy analysis was conducted on the efficacy analysis group, and the efficacy evaluation variables are listed below. The list includes screening number, gender, age, scores for each efficacy evaluation variable, and changes from baseline for each dose group.

[0176] 1) INCAT (Inflammatory Neuropathy Cause and Treatment) disability score: The INCAT disability score is a clinical assessment tool that quantifies the degree of impairment of upper and lower extremity function in CIDP patients. Upper and lower extremity function are each evaluated in 6 levels from 0 to 5 points, and the scores on both sides are added up to produce a total score ranging from 0 to 10 points.

[0177] Upper limb function was assessed according to the following criteria. 0 points were given if the subject had no limitations in using his or her arms and hands in daily life; 1 point was given if symptoms were present in one or both arms but did not affect the ability to perform the following functions (zipping and buttoning clothes, washing or combing hair, using a spoon or chopsticks, exchanging coins); 2 points were given if symptoms were present in one or both arms and affected the functions listed above but did not affect any of them; 3 points were given if symptoms were present in one or both arms and one or two of the functions listed above were impossible; 4 points were given if symptoms were present in one or both arms and caused the disability of three or more of the functions listed above but some voluntary movements were still possible; and 5 points were given if all voluntary movements of both arms were impossible.

[0178] Lower extremity function was evaluated according to the subject's walking ability. 0 points were given for no effect on walking, 1 point for effect on walking but able to walk alone outdoors, 2 points for mainly using unilateral supports (cane, crutches, one arm) when walking outdoors, 3 points for mainly using bilateral supports (two canes, both crutches, a walker, both arms) when walking outdoors, 4 points for mainly using a wheelchair when moving around outdoors but able to stand up and take a few steps with assistance, and 5 points for always relying on a wheelchair when moving and unable to stand up and take a few steps even with assistance.

[0179] The INCAT disability score calculated as described above was used to objectively quantify the subject's neurological function and quantitatively assess the therapeutic effect of the drug. By comparing changes in INCAT disability scores before and after administration of the clinical trial drug, we confirmed whether the subject's function improved.

[0180] 2) MRC (Medical Research Council) total score: The MRC total score (MRC sum score) is an indicator that reflects the subject's whole body muscle strength status. It was performed according to the criteria that grades the muscle strength of each muscle group into 6 levels from 0 to 5 points. A total of 6 muscle groups (arm abduction, forearm flexion, wrist extension, thigh flexion, knee extension, and foot dorsiflexion) were evaluated on both sides (left and right) and then summed.

[0181] Muscle strength grades were defined as follows: 0 points for no visible muscle contraction, 1 point for visible muscle contraction but inability to move the limb, 2 points for moving the limb but not overcoming gravity, 3 points for being able to move against gravity, 4 points for being able to move against gravity and resistance, and 5 points for normal muscle strength.

[0182] Each muscle group was selected as follows. In the upper limb, arm abduction, forearm flexion, and wrist extension were evaluated respectively, and in the lower limb, thigh flexion, knee extension, and foot dorsal flexion were evaluated respectively. Each muscle group was measured independently for the left and right sides, and the muscle strength scores for a total of 12 items (6 muscle groups × both sides) were added together to produce a total MRC score with a maximum of 60 points.

[0183] It was used to quantitatively evaluate the effects of muscle recovery or disease improvement in subjects through changes in the total MRC score before and after administration of the clinical trial drug.

[0184] 3) I-RODS (Inflammatory Rasch-Built Overall Disability Scale): I-RODS is a self-report assessment tool developed to multidimensionally reflect the degree of functional disability in CIDP patients. It consists of a total of 24 items, and each item is evaluated by the subject's subjective response to the ability to perform a specific activity.

[0185] Each item is answered with one of three options based on whether the activity can be performed, typically categorized as "easy" (no difficulty at all), "hard" (ability to perform with some difficulty), or "unable" (unable). The questionnaire was based on the patient's recent experiences in daily life.

[0186] The responses are processed based on a Rasch analysis model, and the results are calculated as a raw score between 0 and 48, reflecting the patient's functional ability, or a converted centile score (0-100 scale). A higher score indicates better functional performance. In this study, the standardized converted centile score was utilized to assess the degree of functional improvement before and after treatment.

[0187] I-RODS is used as an indicator to comprehensively evaluate the treatment response of CIDP patients and has been used to quantitatively demonstrate the functional improvement effect of clinical trial drugs.

[0188] 4) TUG (Timed Up-and-Go): The TUG test is a simple functional examination tool that quantitatively evaluates physical function by measuring a series of movements such as getting up from a chair, walking a set distance, and then sitting back down.

[0189] Specifically, the test began with the subject seated in a chair with a backrest. The time required to stand at the command "Start" and walk 3 meters forward to a marked point, then turn around, return to the starting position, and sit back down was measured in seconds. The test was performed as quickly and safely as possible, and the use of walking aids was permitted if necessary.

[0190] The measured time is defined as a TUG score, with lower times indicating better mobility and balance. Generally, a time of less than 10 seconds is considered normal, while a time of more than 20 seconds may indicate impaired mobility or a risk of falling.

[0191] In the present invention, the TUG score was compared before and after administration of a clinical trial drug to quantitatively evaluate whether the subject's walking and lower extremity function improved.

[0192] 5) Mean grip strength: Grip strength was measured using a hand dynamometer, and the measurement was performed using standardized postures and procedures according to international standards.

[0193] During the measurement, subjects sat on a chair with their backs straight, their arms close to their bodies with their elbows bent at 90 degrees, and their wrists held in a neutral position. Their hands were positioned naturally next to their thighs, and they grasped the handles with their palms facing the body. Each subject performed three repeated measurements on both their right and left hands, with appropriate rest periods between measurements to minimize muscle fatigue.

[0194] Each measured grip strength value was recorded in kPa units, and the values ​​measured from the left and right hands were calculated, and the evaluation was based on the dominant hand.

[0195] In the present invention, the upper limb muscle strength and whole body muscle function status of the subject were quantitatively evaluated by comparing the average grip strength values ​​before and after administration.

[0196] 6) ONLS (Overall Neuropathy Limitations Scale): ONLS is a clinical index for quantitatively evaluating functional impairment in CIDP patients. It is composed of evaluating upper and lower limb functions separately to calculate a total score.

[0197] Upper extremity function is assessed on a 5-point scale, based on the subject's ability to perform everyday tasks with their hands (e.g., grasping objects, putting on a shirt, using eating utensils, etc.). Lower extremity function is assessed on a 7-point scale, and scores are given based on the ability to walk independently, use walking aids, and mobility abilities such as climbing stairs. The upper extremity score ranges from 0 (no limitation) to 5 (loss of function), and the lower extremity score ranges from 0 (no limitation) to 7 (complete limitation of movement). The two items are summed to produce an ONLS score ranging from 0 to 12. A higher score indicates more severe functional limitations.

[0198] In the present invention, the effect of improving daily functions of the upper and lower limbs was quantitatively evaluated by comparing the ONLS scores before and after administration.

[0199] Additionally, 'clinical response' and 'minimum clinically meaningful difference (MCID)-based improvement' were defined and presented as follows:

[0200] 1) Clinical response

[0201] - Improved: For INCAT disability scores, a decrease of 1 or more points compared to baseline.

[0202] - Stable: No change from baseline in INCAT disability score

[0203] - Relapsed: For INCAT disability scores, an increase of 1 or more points compared to baseline.

[0204] 2) Minimal clinically important difference based improvement (MCID)

[0205] - Achieved: If the change from baseline at Visit 5 (Day 14) or Visit 6 (Day 28) meets the criteria in Table 4 at least once.

[0206] - Not Achieved: Other

[0207] Evaluation Variable Criteria: INCAT Disability Score decreased by 1 point or more; MRC Total Score increased by 2 points or more; I-RODSI-RODS Percentile Score increased by 4 points or more; TUG decreased by 4 seconds or more; Average Grip Strength increased by 8 kPa or more; ONLS decreased by 1 point or more

[0208] 3. Pharmacokinetic Analysis Statistical analysis for pharmacokinetic evaluation was conducted on the pharmacokinetic analysis group, and the analysis method was as follows:

[0209] 1) Pharmacokinetic Analyte Concentration-Time Profiles

[0210] Descriptive statistics were calculated for blood concentrations at each time point by dose group. The mean blood concentration-time patterns by dose group were presented in linear and log-linear graphs.

[0211] 2) Pharmacokinetic Variables

[0212] Descriptive statistics were calculated for each dose group for pharmacokinetic evaluation variables. To confirm differences between dose groups, evaluation variables were log-transformed and analysis of variance (general linear model) was performed. At this time, t 1 / 2 The evaluation variables were implemented without log transformation.

[0213] If available, AUC last and C maxPharmacokinetic linearity and dose proportionality were confirmed using evaluation variables. The point estimate of the dose factor and its 90% confidence interval were calculated from the results of the analysis of variance with the log-transformed dose as the independent variable and the log-transformed evaluation variable as the dependent variable. Linearity was confirmed by whether the coefficient was significantly different from 0, and dose proportionality was confirmed by whether the 90% confidence interval of the coefficient was within the range of 1-ln(2.0) / ln(3) to 1+ln(2.0) / ln(3).

[0214] 4. Pharmacodynamic analysis

[0215] Statistical analysis for pharmacodynamic evaluation was conducted on the pharmacodynamic analysis group, and the analysis method was as follows:

[0216] 1) Immunophenotyping

[0217] Descriptive statistics were calculated for each dose group at each time point. The mean blood concentration-time profile for each dose group was presented in a linear graph. Where possible, the Friedman test was performed to identify differences across time points.

[0218] 2) Serum Analyte Profiles

[0219] Descriptive statistics were calculated for each dose group at each time point. The mean blood concentration-time profile for each dose group was presented in a linear graph. Where possible, the Friedman test was performed to identify differences across time points.

[0220] 3) Serum Analyte Profiles 2

[0221] Descriptive statistics were calculated for each dose group at each time point. For continuous data, the mean blood concentration-time profile by dose group was presented in a linear graph. Where possible, the Friedman test (continuous data) or Cochran's Q test (categorical data) was performed to identify differences across time points. Items with three or more categories were further divided into two categories (e.g., No / Yes, Normal / Abnormal, NCS / CS).

[0222] 4) Other Pharmacodynamic Variables

[0223] Descriptive statistics were calculated for each dose group at each time point. Anemia and leukopenia were defined as results for blood hemoglobin and white blood cell (WBC) values ​​below the lower limit of the reference range. For continuous data, the mean blood concentration-time profile by dose group was presented in a linear graph. Where possible, the Friedman test (continuous data) or Cochran's Q test (categorical data) was performed to identify differences across time points. For items with three or more categories, these were further divided into two categories.

[0224] <Example 3> Clinical trial results

[0225] <3-1> Safety assessment results

[0226] A total of 9 subjects received a single intravenous dose of KINE-101, and the doses were 3 for 120 mg KINE-101, 3 for 240 mg, and 3 for 360 mg.

[0227] The results of adverse events (TEAEs) that occurred after KINE-101 administration are shown in Table 5.

[0228] KINE-101 120mg (N=3)KINE-101 240mg (N=3)KINE-101 360mg (N=3)All (N=9)Treatment-emergent adverse event n (%) 1 (33.33) 1 (33.33) 1 (33.33) 3 (33.33) 95% CI (0.84, 90.57) (0.84, 90.57) (0.84, 90.57) (7.49, 70.07) No. of events2114Treatment-emergent adverse event with CTCAE grade≥3n(%)0(0.00)0(0.00)0(0.00)0(0.00)95% CI(0.00, 70.76)(0.00, 70.76)(0.00, 70.76)(0.00, 33.63)No. of events0000Treatment-emergent adverse event leading to deathn(%)0(0.00)0(0.00)0(0.00)0(0.00)95% CI(0.00, 70.76)(0.00, 70.76)(0.00, 33.63)No. of events0000Treatment-emergent serious adverse eventn(%)0(0.00)0(0.00)0(0.00)0(0.00)95% CI(0.00, 70.76)(0.00, 70.76)(0.00, 33.63)No. of events0000Treatment-emergent adverse event leading to treatment discontinuationn(%)0(0.00)0(0.00)0(0.00)0(0.00)95% CI(0.00, 70.76)(0.00, 70.76)(0.00, 70.76)(0.00, 33.63)No. of events0000Acute adverse eventn(%)0(0.00)0(0.00)0(0.00)0(0.00)95% CI(0.00, 70.76)(0.00, 70.76)(0.00, 70.76)(0.00, 33.63)No. of events0000- CI = Confidence Interval- The denominator of the percentage is the number of subjects in each group belonging to the safety population.- The 95% CI was calculated using the Clopper-Pearson exact method.- Adverse events occurring during treatment that led to death: Refers to adverse events occurring during treatment in which the [Serious Adverse Event] item is 'Yes' and the [Serious Adverse Event Category] item is 'Results in death or life-threatening'.- Serious adverse events occurring during treatment: Refers to adverse events occurring during treatment in which the [Serious Adverse Event] item is 'Yes'.- Adverse events occurring during treatment that led to treatment discontinuation: Refers to adverse events occurring during treatment in which the [Action taken with IP] item is recorded as 'Dose interruption'.- Acute adverse events: [After administration of the study drug] [Whether an adverse event was observed within 30 minutes] refers to an adverse event that occurred during treatment marked with ‘Yes’.

[0229] As shown in Table 5, four adverse events occurred in three of the nine subjects (33.33%) in the safety assessment analysis group. No adverse events of CTCAE grade 3 or higher, adverse events leading to death or treatment discontinuation, serious adverse events, or acute adverse events occurred. Furthermore, no clinically significant abnormal findings or changes were observed in vital signs, physical examinations, or electrocardiograms performed in this clinical trial (results not presented).

[0230] The above results indicate that KINE-101 has good safety and tolerability in the dose range of 120 mg to 360 mg when administered intravenously as a single dose in patients with CIDP.

[0231] <3-2> Validity evaluation results

[0232] The change in INCAT disability scores at Visit 5 (Day 14) and Visit 6 (Day 28) compared to the baseline by cohort is shown in Figure 3. The baseline is Visit 2 (Day 1).

[0233] In addition, as described above, improvement in MCID in the INCAT disability score was defined as a 'decrease of 1 point or more', and the clinical response was evaluated by classifying it into 'decrease of 1 point or more - improved', 'no change - stable', and 'increase of 1 point or more - relapsed' for the change in INCAT disability score at Visit 5 (Day 14) and Visit 6 (Day 28) compared to the baseline.

[0234] As a result, as shown in Fig. 4, at Visit 5 (Day 14), the KINE-101 120mg group was 100% 'stable', the 240mg group was 67% 'stable', and 33% 'improved', and the 360mg group was 100% 'improved'. At Visit 6 (Day 28), the KINE-101 120mg group was 100% 'stable', the 240mg group was 67% 'improved', and 33% 'stable', and the 360mg group was 67% 'improved', and 33% 'stable'.

[0235] Additionally, if the INCAT disability score change was 'decreased by 1 point or more' at least once at Visit 5 (Day 14) and Visit 6 (Day 28) compared to the baseline, it was defined as 'Achieved', and if not, it was defined as 'Not Achieved'.

[0236] As a result, as shown in Table 6, all 3 patients in the KINE-101 120 mg group were 'Not Achieved', 2 patients in the 240 mg group were 'Achieved', 1 patient was 'Not Achieved', and all 3 patients in the 360 ​​mg group were 'Achieved'.

[0237] ScreeningNo.DosegroupBaseline(points)Visit 5(Day 14)(points)Visit 6(Day 28)(points)MCID Basedimprovement(Threshold:1 point)ResultChangefrombaselineResultChangefrombaselineS-001KINE-101120mg66060Not AchievedS-002KINE-101120mg66060Not AchievedS-003KINE-101120mg22020Not AchievedS-007KINE-101240mg5504-1AchievedS-008KINE-101240mg33030Not AchievedS-009KINE-101240mg32-12-1AchievedS-010KINE-101360mg31-21-2AchievedS-011KINE-101360mg64-24-2AchievedS-101KINE-101360mg30-330Achieved

[0238] The change in MRC total score at Visit 5 (Day 14) and Visit 6 (Day 28) compared to the baseline by cohort is shown in Figure 5. The baseline is Visit 2 (Day 1).

[0239] In addition, as mentioned above, improvement in MCID in the MRC total score was defined as an 'increase of 2 points or more', and if the change was 'increased by 2 points or more' at least once at Visit 5 (Day 14) and Visit 6 (Day 28) compared to the baseline, it was classified as 'Achieved', and if not, it was classified as 'Not Achieved'.

[0240] As a result, as shown in Table 7, all three subjects in the KINE-101 120 mg group were 'Achieved', two subjects in the 240 mg group were 'Achieved' and one subject was 'Not Achieved', and two subjects in the 360 ​​mg group were 'Achieved' and one subject was 'Not Achieved'. However, in the case of subjects classified as 'Not Achieved', the MRC score was already full (60 points) at baseline, making further score improvement impossible.

[0241] ScreeningNo.DosegroupBaseline(Fullscore: 60)(points)Visit 5(Day 14)(points)Visit 6(Day 28)(points)MCID Basedimprovement(Threshold:2 points)ResultChangefrombaselineResultChangefrombaselineS-001KINE-101120mg40466444AchievedS-002KINE-101120mg5052 2566AchievedS-003KINE-101120mg56582582AchievedS-007KINE-101240mg4456125511AchievedS-008KINE-101240mg48480480Not AchievedS-009KINE-101240mg54584562AchievedS-010KINE-101360mg60600600Not AchievedS-011KINE-101360mg3246144614AchievedS-101KINE-101360mg49589512Achieved

[0242] The I-RODS scores and changes compared to the baseline at Visit 5 (Day 14) and Visit 6 (Day 28) for each cohort were converted to percentile scores and the percentile score changes are shown in Figure 6. The baseline is Visit 2 (Day 1).

[0243] Additionally, as previously described, improvement in MCID in the I-RODS percentile score was defined as a "4-point or greater increase." A 4-point or greater increase in I-RODS score at least at Visit 5 (Day 14) or Visit 6 (Day 28) compared to baseline was classified as "Achieved," while other increases were classified as "Not Achieved."

[0244] As a result, as shown in Table 8, in the KINE-101 120 mg group, 1 subject was 'Achieved' and 2 subjects were 'Not Achieved', and in the 240 mg group, all subjects (3 subjects) were confirmed as 'Achieved'. In the 360 ​​mg group, 2 subjects were 'Achieved' and 1 subject was 'Not Achieved'. Among the 3 subjects classified as 'Not Achieved', 1 subject already had a perfect I-RODS score at baseline, so further score improvement was not possible.

[0245] ScreeningNo.DosegroupBaseline rawscore(Fullscore: 48)(points)Baselinecentile scoreby the centilemetric[1](Fullscore: 100)(points)Visit 5(Day 14)(points)Visit 6(Day 28)(points)MCID Basedimprovement(Threshold: 4centile points)Raw score / Centile scoreChange frombaseline incentile scoreRaw score / Centile scoreChange frombaseline incentile scoreS-001KINE-101120mg224225 / 46425 / 464AchievedS-002KINE-101120mg224223 / 43123 / 431Not AchievedS-003KINE-101120mg4810048 / 100048 / 1000Not AchievedS-007KINE-101240mg264730 / 52530 / 525AchievedS-008KINE-101240mg295134 / 58734 / 587AchievedS-009KINE-101240mg417143 / 76543 / 765AchievedS-010KINE-101360mg437643 / 76044 / 804AchievedS-011KINE-101360mg224222 / 42022 / 420Not AchievedS-101KINE-101360mg305244 / 802814 / 32-20Achieved[1] van Nes SI, Vanhoutte EK, van Doorn PA, Hermans M, Bakkers M, Kuitwaard K, Faber CG, Merkies IS. Rasch-built Overall Disability Scale(R-ODS) for immune-mediated peripheral neuropathies. Neurology. 2011 Jan 25;76(4):337-45.。

[0246] The changes in TUG scores at Visit 5 (Day 14) and Visit 6 (Day 28) compared to the baseline by cohort are shown in Figure 7. The baseline is Visit 2 (Day 1).

[0247] Additionally, as previously described, improvement in MCID in the TUG score was defined as a "4-second or greater reduction." If the change in MCID was at least once "4-second or greater reduction" compared to baseline at Visit 5 (Day 14) and Visit 6 (Day 28), the criteria were classified as "Achieved." Otherwise, the criteria were classified as "Not Achieved."

[0248] As a result, as shown in Table 9, in the KINE-101 120 mg group, 1 person was 'Achieved' and 2 people were 'Not Achieved', and in the 240 mg group, 2 people were 'Achieved' and 1 person was 'Not Achieved'. In the 360 ​​mg group, excluding 1 person whose test result was missing, 1 person was 'Achieved' and 1 person was 'Not Achieved'. Of the 4 subjects who were 'Not Achieved', 2 had TUG scores at baseline of 10.5 seconds and 10.68 seconds, respectively, which were close to the normal range, and during the clinical trial, their scores decreased by up to 2.25 seconds and 3.42 seconds, respectively, showing improvements of 21.4% and 32.02%, respectively. This resulted in TUG scores for both subjects falling within the normal range (less than 10 seconds), and these changes can be interpreted as clinically significant.

[0249] ScreeningNo.DosegroupBaseline(NormalRange: ≤10seconds)(seconds)Visit 5(Day 14)(seconds)Visit 6(Day 28)(seconds)MCID Basedimprovement(Threshold:4 seconds)ResultChangefrombaselineResultChangefrombaselineS-001KINE-101120mg34.9225.52-9.429-5.92AchievedS-002KINE-101120mg607818Not AchievedS-003KINE-101120mg7.687.6-0.086.93-0.75Not AchievedS-007KINE-101240mg45.5713.12-32.4513.64-31.93AchievedS-008KINE-10124 0mg18.7513.7-5.0513.55-5.2AchievedS-009KINE-101240mg10.58.25-2.258.51-1.99Not AchievedS-010KINE-101360mg10.687.27-3.417.26-3.42Not AchievedS-011KINE-101360mg-S-101KINE-101360mg126-69-3Achieved

[0250] The average grip strength at Visit 5 (Day 14) and Visit 6 (Day 28) compared to the baseline for each cohort was evaluated for the left and right hands, respectively, and is shown in Figure 8 for the dominant hand. The baseline is Visit 2 (Day 1).

[0251] Additionally, as previously described, improvement in MCID in the mean grip strength score was defined as an increase of 8 kPa or more. If the change in the mean grip strength score was at least 8 kPa more than once at Visit 5 (Day 14) and Visit 6 (Day 28) compared to baseline, the score was classified as "Achieved." Otherwise, the score was classified as "Not Achieved."

[0252] As a result, as shown in Table 10, in the KINE-101 120 mg group, there were 2 'Achieved' and 1 'Not Achieved', in the 240 mg group, there were 2 'Achieved' and 1 'Not Achieved', and in the 360 ​​mg group, there were 1 'Achieved' and 2 'Not Achieved'.

[0253] ScreeningNo.DosegroupLeft / RightBaseline(kPa)Visit 5(Day 14)(kPa)Visit 6(Day 28)(kPa)Dominant handMCID Basedimprovement(Threshold:8 kPa)ResultChangefrombaselineResultChangefrombaselineS-001KINE-101120mgRight19.33222.6722.663.33YesNot AchievedLeft16.66181.34203.34NoNot AchievedS-002KINE-101120mgRight15.3322.667.332812.67YesAchievedLeft13.33162.6718.665.33NoNot AchievedS-003KINE-101120mgRight57.33624.677012.67YesAchievedLeft59.3361.332666.67NoNot AchievedS-007KINE-101240mgRight19.335232.6761.3342YesAchievedLeft16503462.6646.66NoAchievedS-008KINE-101240mgRight25.3322-3.33282.67YesNot AchievedLeft1820.662.6626.668.66NoAchievedS-009KINE-101240mgRight49.337424.6771.3322YesAchievedLeft49.3372.6623.337222.67NoAchievedS-010KINE-101360mgRight7447.33-26.6760-14YesNot AchievedLeft6443.33-20.6753.33-10.67NoNot AchievedS-011KINE-101360mgRight43.3338.66-4.67484.67YesNot AchievedLeft39.3338.66-0.67422.67NoNot AchievedS-101KINE-101360mgRight253492.5-22.5YesAchievedLeft23.333410.673.33-20NoAchieved

[0254] The changes in ONLS scores at Visit 5 (Day 14) and Visit 6 (Day 28) compared to the baseline by cohort are shown in Figure 9. The baseline is Visit 2 (Day 1).

[0255] Additionally, as previously described, improvement in the MCID in the ONLS score was defined as a "decrease of 1 point or more." If the change in the MCID was at least 1 point decrease at Visit 5 (Day 14) and Visit 6 (Day 28) compared to baseline, the score was classified as "Achieved." Otherwise, the score was classified as "Not Achieved."

[0256] As a result, as shown in Table 11, all three patients in the KINE-101 120 mg group were ‘Not Achieved’, but all three patients in the 240 mg group and all three patients in the 360 ​​mg group were ‘Achieved’.

[0257] ScreeningNo.DosegroupBaseline(points)Visit 5(Day 14)(points)Visit 6(Day 28)(points)MCID Basedimprovement(Threshold: 1point)Any disorder(Comment)ResultChangefrombaselineResultChangefrombaselineS-001KINE-101120mg66060Not AchievedNoS-002KINE-101120mg66060Not AchievedNoS-003KINE-101120mg11010Not AchievedNoS-007KINE-101240mg65-15-1AchievedNoS-008KINE-101240mg41-32-2AchievedNoS-009KINE-101240mg43-12-2Achi evedNoS-010KINE-101360mg31-22-1AchievedNoS-011KINE-101360mg76-16-1AchievedNoS-101KINE-101360mg43-140AchievedNo

[0258] The above results show that KINE-101 induces clinically meaningful improvements in six major functional indices of INCAT, MRC, I-RODS, TUG, mean grip strength, and ONLS with a single intravenous administration in CIDP patients, with consistent overall response direction and pattern.

[0259] <3-3> Pharmacokinetic analysis results

[0260] The average blood concentration-time pattern by cohort is shown in Figure 10.

[0261] Additionally, descriptive statistics for pharmacokinetic evaluation variables by cohort after a single intravenous administration of KINE-101 are presented in Table 12.

[0262] As shown in Table 12, pharmacokinetic evaluation variables were log-transformed (but t 1 / 2 As a result of performing ANOVA (without log transformation), AUClast The difference between cohorts was statistically significant.

[0263] KINE-101Cohort 1(N=3)Cohort 2(N=3)Cohort 3(N=3)C max (ug / L)n333Arithmetic mean162.3326.3448.0Standard deviation156.574.33138.7Geometric mean121.0320.9431.4Coefficient of variation96.522.831.0Median74.30305.0522.0AUC last (min*ug / L)n333Arithmetic mean2600741311343Standard deviation208216654603Geometric mean2125729710573Coefficient of variation80.122.540.6Median1630659013900AUC inf (min*ug / L)n101Arithmetic mean499014100Standard deviationGeometric mean499014100Coefficient of variationMedian499014100CL(L / min)n333Arithmetic mean66.5733.3036.93Standard deviation39.496.71019.63Geometric mean56.5132.8133.93Coefficient of variation59.320.253.2Median73.7036.4025.70t1 / 2(min)n101Arithmetic mean1.6401.460Standard deviationGeometric mean1.6401.460Coefficient of variationMedian1.6401.460

[0264] In addition, the results of the pharmacokinetic linearity evaluation by cohort are shown in Table 13. As a result, as shown in Table 13, AUC in the single dose range of KINE-101 (120 to 360 mg)last and C max All dose factor coefficients were significantly different from 0, confirming pharmacokinetic linearity. In addition, the 90% confidence intervals for all items included 1.

[0265] Geometric least squares meanCoefficient for dose90% Clower limit90% Clupper limitCohort 1Cohort 2Cohort 3Pointestimatep-valueAUC last( min*ug / L)22416317115801.49480.00520.78772.2019C max( ug / L)126.1286.6463.31.18410.02020.43381.9344

[0266] The above results show that KINE-101 maintains a consistent trend of increasing drug exposure with increasing dose, indicating that KINE-101 has predictable pharmacodynamic characteristics.

[0267] <3-3> Pharmacodynamic analysis results

[0268] The results of immunophenotypic analysis at Visit 5 (Day 14) and Visit 6 (Day 28) by cohort are shown in Figure 11.

[0269] Additionally, the results of serum analysis at Visit 5 (Day 14) and Visit 6 (Day 28) by cohort are shown in Figure 12, and the results of serum analysis 2 are shown in Figure 13.

[0270] As a result, as shown in Fig. 11, a significant increase between time points was confirmed in FoxP3 MMI of the KINE-101 240 mg group and CCR5 MMI of the KINE-101 360 mg group.

[0271] In addition, as shown in Fig. 12, significant changes in both IL-6 and TGF-β were observed between time points in the KINE-101 360 mg group, and in particular, a decrease in IL-6 and an increase in TGF-β were observed.

[0272] Additionally, as shown in Figure 13, a significant increase in C4 complement between time points was confirmed in the KINE-101 120 mg group.

[0273] The above results indicate that KINE-101 induces a series of immunological cascades, including activation of regulatory T cells, including significant increases in the expression of FoxP3 and CCR5, followed by secretion of anti-inflammatory cytokines (TGF-β) and suppression of inflammatory cytokines (IL-6).

[0274] Through the results of the above <Examples 1> to <Examples 3>, it can be seen that the peptide according to the present invention exhibits excellent safety and tolerability in CIDP patients with only a single intravenous administration, and induces clinically meaningful improvements (based on MCID) in multiple functional indicators according to the regulatory T cell-based immunoregulatory mechanism.

[0275] According to the present invention, since a safe and excellent effect can be obtained in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) by intravenously administering an injectable preparation containing the peptide of the present invention to a patient with CIDP, the administration regimen of the peptide according to the present invention can be usefully used in the treatment of CIDP.

Claims

1. A pharmaceutical composition for treating chronic inflammatory demyelinating polyneuropathy (CIDP), comprising a peptide consisting of an amino acid sequence represented by sequence number 1 or a pharmaceutically acceptable salt thereof, wherein the peptide or the pharmaceutically acceptable salt thereof is administered intravenously.

2. A pharmaceutical composition according to claim 1, wherein the salt is an acetate salt.

3. A pharmaceutical composition according to claim 1, wherein the peptide or a pharmaceutically acceptable salt thereof is administered intravenously in a dosage of 120 mg to 360 mg.

4. A pharmaceutical composition according to claim 1, wherein the composition is administered intravenously to a subject having CIDP.

5. A pharmaceutical composition according to claim 4, wherein the subject is a subject with CIDP that is refractory to corticosteroid treatment.

6. A pharmaceutical composition according to claim 4, wherein administration of the composition improves at least one of the following indicators in the subject: 1) INCAT (Inflammatory Neuropathy Cause and Treatment) disability score; 2) MRC (Medical Research Council) total score; 3) I-RODS (Inflammatory Rasch-Built Overall Disability Scale); 4) TUG (Timed Up-and-Go); 5) Mean grip strength; and 6) ONLS (Overall Neuropathy Limitations Scale).

7. A pharmaceutical composition according to claim 6, wherein the INCAT disability score is reduced by 1 point or more compared to baseline by administration of the composition.

8. A pharmaceutical composition according to claim 6, wherein the MRC total score increases by 2 or more points compared to baseline by administration of the composition.

9. A pharmaceutical composition according to claim 6, wherein the I-RODS percentile score increases by 4 points or more compared to baseline by administration of the composition.

10. A pharmaceutical composition according to claim 6, wherein administration of the composition reduces TUG by 4 seconds or more compared to baseline.

11. A pharmaceutical composition according to claim 6, wherein the average grip strength increases by 8 kPa or more by administration of the composition.

12. A pharmaceutical composition according to claim 6, wherein the ONLS score decreases by 1 point or more compared to baseline by administration of the composition.

13. A pharmaceutical composition according to claim 6, wherein the administration of the composition results in improvement in the subject for more than 4 weeks.

14. A pharmaceutical composition according to claim 1, wherein the composition is administered intravenously once or multiple times.

15. A pharmaceutical composition according to claim 1, wherein the composition is formulated as an injection.

16. In paragraph 15, the injection agent buffer; pH adjuster; Topic of appearance; and A pharmaceutical composition containing a surfactant.

17. A pharmaceutical composition according to claim 16, wherein the buffer is at least one of sodium hydrogen phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate monohydrate, phosphate buffer, histidine / histidine hydrochloride buffer, and sodium citrate / citric acid buffer.

18. A pharmaceutical composition according to claim 16, wherein the pH adjusting agent is at least one of sodium hydroxide, hydrochloric acid, tromethamine, lactic acid, acetic acid, and citric acid.

19. A pharmaceutical composition according to claim 16, wherein the tonicity agent is contained in an amount of 0.1 to 2 w / v% with respect to the total injection amount.

20. A pharmaceutical composition according to claim 16, wherein the isostatic agent is sodium chloride.

21. A pharmaceutical composition according to claim 16, wherein the surfactant is contained in an amount of 0.001 to 0.1 w / v% based on the total injection amount.

22. A pharmaceutical composition according to claim 16, wherein the surfactant is polysorbate 20 or polysorbate 80.

23. A method for treating chronic inflammatory demyelinating polyneuropathy (CIDP), comprising the step of intravenously administering to a subject a pharmaceutical composition comprising a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof.

24. For use in manufacturing a pharmaceutical composition for treating chronic inflammatory demyelinating polyneuropathy (CIDP), The pharmaceutical composition comprises a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof, wherein the peptide or the pharmaceutically acceptable salt thereof is administered intravenously.

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