A tool for preliminary evaluation of the efficacy of oral complement B factor inhibitors in PNH patients.

Abstract

In the field of medical device technology, we provide a preliminary evaluation tool for the therapeutic effect of oral complement B factor inhibitors on patients with PNH. [Solution] An indicator recording area 2, a status indication area 3, and a time marking band 4 are arranged on the front of the housing 1. The indicator recording area has a horizontal scale bar 5 for recording hemoglobin values ​​and a multi-week corresponding recording frame 6 for recording transfusion frequency. The status indication area has a manually switchable window that displays the status of intravascular hemolysis, extravascular hemolysis, and overall effect in different colors. The time marking band has date positions corresponding to the recording week. This allows for centralized recording of key indicators in the initial stages of treatment, enables visual understanding of changes over time, and supports preliminary evaluation of the effect. This solves the problem that, in basic medical care and follow-up settings, when evaluating the effect of oral complement factor B inhibitor therapy on PNH patients, laboratory indicators and subjective symptoms are dispersed, making systematic recording and intuitive understanding of treatment trends difficult.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical devices, and particularly relates to an instrument for preliminarily evaluating the effect of an oral complement factor B inhibitor in patients with PNH.

Background Art

[0002] Paroxysmal Nocturnal Hemoglobinuria (hereinafter referred to as PNH) is a rare acquired hematopoietic stem cell clonal disease caused by somatic acquired mutations in the Phosphatidylinositol N-acetylglucosaminyltransferase subunit A (hereinafter referred to as PIGA) gene on the X chromosome. Mutations in the PIGA gene cause defects in the synthesis of Glycosylphosphatidylinositol (hereinafter referred to as GPI), resulting in the deficiency of more than 20 types of GPI-anchored proteins (such as CD55, CD59, CD14, CD16, etc.) on the surface of hematopoietic stem cells and their progeny cells. Among them, the deficiency of CD55 and CD59, which are complement regulatory factors, leads to the continuous activation of the complement system and the failure to suppress it, which is the main pathogenesis of PNH. The clinical symptoms of PNH patients are characterized by multi-organ dysfunction such as hemolytic anemia, thrombosis tendency, and bone marrow hypoplasia. According to the criteria of the International PNH Interest Group, PNH is classified into the following three types: classical type (with typical hemolysis or thrombosis), type combined with bone marrow hypoplasia disease, and subclinical type (without clinical or laboratory evidence of hemolysis or thrombosis, but having a small amount of PNH clones).

[0003] Currently, PNH treatment research has entered the "post-C5 inhibitor era." C5 terminal complement inhibitors, such as eculizumab and ravulizumab, significantly suppress intravascular hemolysis, reduce the incidence of thrombotic events, and improve the quality of long-term survival in patients by inhibiting the formation of membrane attack complexes (MACs). For example, in a prospective observational study, eculizumab treatment reduced the incidence of major adverse vascular events (MAVEs) in PNH patients with high disease activity (HDA) from 5.4 / 100 person-years at baseline to 1.0 / 100 person-years at the end of follow-up, while no significant change was observed in the untreated group. Furthermore, eculizumab treatment improved patients' hemoglobin levels and reduced the need for blood transfusions. However, while C5 inhibitors such as eculizumab and ravulizumab effectively prevent red blood cell destruction, reduce transfusion needs, and improve quality of life in PNH patients, 35-40% of patients still face challenges such as persistent anemia, transfusion dependence, and a reduced quality of life due to the persistent deposition of C3 fragments upstream of complement activation on the surface of PNH red blood cells after treatment, leading to extravascular hemolysis mediated by hepatosplenic macrophages. This unmet clinical need has spurred the development of drugs targeting further upstream in the complement system. Among these, the development of iptacopan, an oral complement factor B inhibitor, represents a groundbreaking advance. Results from Phase III clinical trials (APPLY-PNH and APPOINT-PNH) showed that ipsicapan monotherapy was not only effective in patients with persistent anemia after C5 inhibitor treatment, but also significantly increased hemoglobin levels (hemoglobin normalized in approximately two-thirds of patients), achieved an extremely high transfusion avoidance rate, and significantly improved patient-reported fatigue scores. Results from the international Phase III clinical trial APPOINT-PNH showed that after 24 weeks of treatment, hemoglobin levels significantly increased in the vast majority of patients (92.2%), reaching 12 g / dL or higher in 62.8% of patients, demonstrating effective control of hemolysis.Furthermore, almost all (97.6%) of the patients participating in the study avoided blood transfusions, and patient-reported fatigue was significantly reduced. Its mechanism of action is to specifically inhibit the amplification loop of the complement alternative pathway, thereby simultaneously preventing both intravascular and extravascular hemolysis.

[0004] As described above, oral complement factor B inhibitors have shown potential in clinical studies to suppress both intravascular and extravascular hemolysis as a novel therapeutic approach targeting the complement alternative pathway. However, in actual clinical application, there is a lack of intuitive tools for systematic recording and early preliminary assessment of treatment efficacy in PNH patients receiving factor B inhibitor therapy. Existing evaluation methods largely rely on laboratory indicators and subjective symptom reports, making it difficult to rapidly and systematically integrate important indicators and intuitively reflect trends in treatment response in basic medical care and follow-up settings. [Overview of the project] [Problems that the invention aims to solve]

[0005] This invention provides a tool for preliminary evaluation of the effects of oral complement factor B inhibitors in patients with PNH. It aims to enable systematic recording of important indicators of treatment response in the early stages and intuitive and standardized preliminary evaluation of trends in patients with paroxysmal nocturnal hemoglobinuria receiving factor B inhibitor therapy, thereby solving the problems of data dispersion, difficulty in trend tracking, and inconvenience of systematic application in basic medical care and follow-up settings that arise in current clinical practice due to reliance on laboratory indicators and subjective symptom reports. [Means for solving the problem]

[0006] To achieve the above objective, this invention employs the following technical solution: A tool for preliminary evaluation of the efficacy of oral complement factor B inhibitors in PNH patients is: The casing and The front of the housing is divided into an upper region, a middle region, and a lower region. An indicator recording area is provided in the upper area of ​​the front of the housing, and the indicator recording area includes a horizontal scale bar for marking the current hemoglobin value and a transfusion frequency recording frame for recording the weekly transfusion frequency, and the transfusion frequency recording frame includes a plurality of recording units corresponding to consecutive weeks, A status indication area is provided in the central region of the front of the housing, and this status indication area includes an intravascular hemolysis status window, an extravascular hemolysis status window, and an overall effect window, which are arranged in parallel, and each window has a manually switchable status indicator piece to display a different color, with the different colors representing the corresponding clinical state. A time marking zone is provided in the lower region of the front of the housing, and multiple date identification positions are provided on the time marking zone, the number of which is equal to the number of recording units of the transfusion frequency record frame and corresponding to the number of date identification positions. It is characterized by the following:

[0007] In the state indication area, a rotation axis is provided in the frame of each window, and the state indication piece is mounted in the window via the rotation axis so as to be reversible.

[0008] Within each recording unit of the aforementioned transfusion frequency recording frame, multiple marking positions are provided, each representing a different number of transfusions. [Effects of the Invention]

[0009] This invention enables the systematic collection and trend presentation of early treatment data by integrating important indicator records with visualized status indications. It centralizes dispersed hemoglobin test values, weekly transfusion events, and hemolysis status determined based on clinical indicators onto a portable physical medium. The indicator recording area features a continuous horizontal hemoglobin scale bar and a transfusion frequency recording frame precisely corresponding to the week of time, allowing for direct marking of important quantitative data at each follow-up on a unified timeline. The status indication area converts qualitative judgments of intravascular hemolysis, extravascular hemolysis, and overall effect into intuitive color signals via manually reversible, double-sided color strips representing different clinical states. This design allows patients or healthcare professionals to continuously and structurally record important response indicators over a 12-week initial treatment period and directly observe the dynamic trends of each indicator over time, overcoming the problems of record confusion and difficulty in trend identification resulting from reliance on conventional dispersed test charts and subjective memory.

[0010] This invention employs standardized physical indicator components and clear judgment criteria, contributing to the unification of preliminary judgment criteria for effectiveness and improved consistency of evaluation. The status indicator area of ​​the device has pre-set specific color identifications and corresponding laboratory index threshold criteria (e.g., LDH > 1.5 times the upper limit of normal corresponds to red) for core clinical conditions (intravascular / extravascular hemolysis, overall effect). Based on objective test results, the user needs to manually flip the status indicator piece to display the color corresponding to the condition. This physical operation requires the user to make judgments against established criteria, reducing evaluation bias due to differences in individual experience and subjective sensitivity. The three parallel color indicator windows provide clear status divisions, enabling different users (e.g., local physicians, the patient themselves, or family members) to operate based on the same visualized criteria when recording in different situations, thereby increasing the normativity of the preliminary effectiveness evaluation process and the comparability between different records.

[0011] The entire device of this invention employs a waterproof and fold-resistant housing, is covered with an anti-reflective transparent protective film, and has rounded edges, ensuring good physical durability and safety. All of its functions are achieved through simple manual operations such as scale marking, check recording, color inversion, and magnetic tag replacement, requiring no power supply, software, or complex training. The time marking band and the transfusion record frame cycle are perfectly aligned, and the temporal accuracy of the recording is ensured by corresponding the actual treatment start date with replaceable magnetic date tags. With this design, the device is particularly suitable for situations such as basic healthcare facilities, home self-management, and telemedicine follow-up, where advanced medical equipment and specialized data systems may be lacking, and can function as a stable, intuitive, and low-cost auxiliary recording means to support long-term tracking of treatment response. [Brief explanation of the drawing]

[0012] [Figure 1] Figure 1 is a perspective view showing the overall configuration of the present invention. [Figure 2] Figure 2 is an enlarged detailed diagram of the state indication area. [Figure 3] Figure 3 is a diagram showing the configuration of the back of the enclosure. [Modes for carrying out the invention]

[0013] In the following, the technical solution in the embodiment of the present invention will be clearly and completely explained with reference to the drawings attached to the embodiment of the present invention.

[0014] Please refer to Figures 1 to 3. This invention provides a device for preliminary evaluation of the effects of oral complement factor B inhibitors in patients with paroxysmal nocturnal hemoglobinuria (PNH). As a whole, this device, a portable physical recording device, is used by patients, their families, or basic healthcare professionals to systematically and visually record key indicators in the early stages of treatment and observe trends during the course of treatment with factor B inhibitors in patients with paroxysmal nocturnal hemoglobinuria.

[0015] The aforementioned device includes a housing 1, an indicator recording area 2, a status indication area 3, and a time marking band 4. The housing 1 has a rectangular structure and is made of a waterproof, foldable material of polypropylene or polyester, with dimensions of 210 mm in length, 150 mm in width, and a thickness between 0.8 mm and 1.2 mm. Its four corners are rounded and chamfered, and its edges are covered with flexible silicone bumpers to prevent structural damage or skin injury due to friction or bending during long-term use. The front of the housing 1 is divided into an upper area, a middle area, and a lower area from top to bottom, with the indicator recording area 2, the status indication area 3, and the time marking band 4 correspondingly installed in each.

[0016] The indicator recording area 2 is located in the upper area of ​​the front of the housing 1 and includes a hemoglobin horizontal scale bar 5 and a transfusion frequency recording frame 6. The hemoglobin horizontal scale bar 5 is positioned horizontally, with "less than 70 g / L" indicated at the left end and "greater than 130 g / L" at the right end, and scale lines drawn at 5 g / L intervals in the middle. In accordance with clinical standards, the scale lines at the 90 g / L and 110 g / L positions are thickened and highlighted to clearly indicate the diagnostic threshold for anemia. Below the hemoglobin horizontal scale bar 5, there is an additional reference line, which corresponds precisely to the 110 g / L scale and functions as a visual indication of the treatment target level. This is independent of the diagnostic criteria for the anemia threshold reference area and provides reference information together. The user marks the current numerical position directly on the hemoglobin horizontal scale bar 5 based on the laboratory report. The use of an erasable pen is recommended.

[0017] The transfusion frequency record frame 6 is located directly below the horizontal hemoglobin scale bar 5 and consists of 12 horizontally arranged squares. Each square represents a one-week time cycle, corresponding to weeks 1 through 12 from left to right, and perfectly aligns with the 12-week cycle of the time marking zone 4. Inside each square are three concentric rings: the innermost ring represents "0" transfusions for that week, the middle ring represents "1" transfusion, and the outermost ring represents "2 or more (≧2)" transfusions. Based on the actual transfusion situation, the user completes the transfusion frequency record for the week by marking or filling in the corresponding ring using a recommended erasable pen. This design ensures that transfusion frequency is systematically recorded throughout the entire 12-week evaluation period.

[0018] The status indication area 3 is located in the central region of the front of the housing 1 and includes three parallel color indicator windows: an intravascular hemolysis status window, an extravascular hemolysis status window, and an overall effect window. A rotation axis is provided on the outer frame of each color indicator window, and the double-sided color pieces are rotatably connected to the outer frame via this rotation axis. Positioning clicks or minute magnetic attraction points are provided on the rotation axis portion, which lightly fix or attract the color piece when it is flipped to a predetermined position (i.e., when a certain color side is fully displayed), maintaining a stable state. A knob (retractable protruding tab) is provided on the edge of the color piece for operation, making it easy for the user to grasp and flip the color piece with their fingers. In the double-sided color piece within the intravascular hemolysis status window, one side is red and the other is green, and when the red side is facing outward, it indicates the presence of hemoglobinuria or elevated lactate dehydrogenase (LDH) (clinical judgment reference: e.g., LDH > 1.5 times the upper limit of normal). When the green side is facing outward, it indicates that the aforementioned indicator is stable (e.g., LDH ≤ 1.5 times the upper limit of normal and no hemoglobinuria). In the extravascular hemolysis state window, if the bilateral colored piece has one side orange and the other blue, and the orange side is facing outward, it indicates elevated reticulocyte count or abnormal indirect bilirubin (clinical judgment reference: e.g., reticulocyte percentage > upper limit of normal or elevated indirect bilirubin). When the blue side is facing outward, it indicates that the related indicator is moving towards normal. In the overall effect window, if the bilateral colored piece has one side yellow and the other purple, and the yellow side is facing outward, it indicates that the treatment response is unclear or that further observation is needed (clinical judgment reference: e.g., hemoglobin does not show a sustained upward trend or transfusion is still needed). When the purple side is facing outward, it indicates that hemoglobin is steadily increasing and transfusion is not needed. To assist in decision-making, the tool comes with a separate reference card that lists the recommended thresholds and decision points mentioned above. The color settings for the three color indicator windows conform to internationally recognized warning and safety color scheme standards, ensuring the intuitiveness and consistency of the color signals.

[0019] The time marking band 4 is provided in the lower region of the front of the housing 1 and is a strip-shaped region extending horizontally. On its surface, 12 equally spaced date insertion slots are provided, each slot corresponding to a one-week treatment cycle and being marked as the 1st week to the 12th week in order from left to right. At the start of the time marking band 4, there is a display of "Treatment start date", and at the end, there is a display of "12th week", clarifying the range of the time axis. A paper label with a specific date can be inserted into each date insertion slot. The back surface of the paper label is coated with an iron powder layer, and a magnetic back layer is provided at the bottom of the slot to realize temporary fixation of the label by magnetic adsorption force. This enables flexible adjustment of the Gregorian calendar dates corresponding to each week according to the actual treatment start date. The label can be repeatedly removed and replaced, supporting continuous use over multiple follow-up cycles.

[0020] On the back of the housing 1, a patient information entry area is provided. This area is divided by intaglio-printed lines into five independent columns: a name column, a medical record number column, a treatment start date column, a drug name column, and a attending physician signature column. The entry content in the "Treatment start date column" must be made to match the date label first inserted into the time marking band 4. The intaglio-printed lines form a shallow groove structure to guide the entry position and prevent misalignment or duplication of the entry content.

[0021] The entire front of the housing 1 is covered with a transparent protective film. This transparent protective film is made of polyethylene terephthalate material and is sealed and joined to the edge of the housing 1 by a thermocompression bonding process to form a sealed protective layer. The surface of the transparent protective film is subjected to an anti-glare treatment to reduce the reflection of ambient light and avoid difficulty in reading under strong light.

[0022] During the usage process, on the treatment start date of the factor B inhibitor, the patient first inserts a paper label with the treatment start date filled in the first slot of the time marking zone 4, and records basic information (especially the treatment start date) in the patient information filling area on the back. During the weekly follow-up, based on the laboratory test results of that week, use a erasable pen to mark the corresponding numerical value on the hemoglobin level scale bar 5. Based on the blood transfusion record, use a erasable pen to fill in a check mark in the corresponding circle within the corresponding square of the blood transfusion frequency record frame 6. At the same time, based on the changes in the hemolysis-related indicators of that week, refer to the attached threshold guide, manually reverse both color patches in the three color label windows, and display the color corresponding to the current state. Through the above operations, this device integrates scattered clinical data and subjective experiences into a unified, continuous, and visible recording interface, forming an effect trend diagram covering the entire 12-week treatment process.

[0023] This device realizes information recording and simple trend presentation completely depending on the physical structure. The design ensures that different users can obtain a unified recording format and observation criteria in various medical scenarios (such as community clinics, home follow-up, telemedicine, etc.), and effectively overcomes problems such as data dispersion, difficulty in continuous tracking, and inconvenience in application in non-specialized scenarios that the conventional evaluation methods have. The completeness of the blood transfusion frequency record and the stability design of each component guarantee the continuous reliability of the data.

[0024] In summary, this invention helps clinicians provide specific information regarding clinical prognosis to patients and their families, and contributes to reducing patients' anxiety and the impact of the disease on daily life.

Description of Reference Numerals

[0025] 1 Housing 2 Indicator Recording Area 3 Status Indication Area 4 Time Marking Zone 5 Hemoglobin Level Scale Bar 6 Blood Transfusion Frequency Record Frame

Claims

1. A device for preliminary evaluation of the effects of oral complement B factor inhibitors in PNH patients, The casing and The front of the housing is divided into an upper region, a middle region, and a lower region. An indicator recording area is provided in the upper area of ​​the front of the housing, and the indicator recording area includes a horizontal scale bar for marking the current hemoglobin value and a transfusion frequency recording frame for recording the weekly transfusion frequency, and the transfusion frequency recording frame includes a plurality of recording units corresponding to consecutive weeks, A status indication area is provided in the central region of the front of the housing, and this status indication area includes an intravascular hemolysis status window, an extravascular hemolysis status window, and an overall effect window, which are arranged in parallel, and each window has a manually switchable status indicator piece to display a different color, with the different colors representing the corresponding clinical state. A time marking zone is provided in the lower region of the front of the housing, and multiple date identification positions are provided on the time marking zone, the number of date identification positions being equal to the number of recording units of the transfusion frequency recording frame and corresponding to each other. A device characterized by its ability to preliminarily evaluate the efficacy of oral complement B factor inhibitors in PNH patients.

2. In the state indication area, a pivot axis is provided in the frame of each window, and the state indication piece is mounted in a reversible manner within the window via the pivot axis. A device for preliminary evaluation of the effect of an oral complement factor B inhibitor on PNH patients as described in feature 1.

3. Within each recording unit of the aforementioned transfusion frequency recording frame, multiple marking positions are provided, each representing a different number of transfusions. A device for preliminary evaluation of the effect of an oral complement factor B inhibitor on PNH patients as described in feature 1.

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