Study of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein (FRSW107) On-Demand Treatment

Официальное название

A Single-arm, Open-label, Multicenter Phase III Clinical Study Evaluating the Efficacy, Safety, and Immunogenicity of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein (FRSW107) On-demand Treatment in Patients With Severe Hemophilia A (Adults and Adolescents) .

Обзор

The indication for this product is to control bleeding in patients with hemophilia A (congenital deficiency of factor VIII). The primary objective: Evaluation of the efficacy of recombinant human coagulation factor VIII-Fc fusion protein for injection (FRSW107) as an on-demand treatment in previously treated patients with severe hemophilia A. Secondary objectives: Evaluation of the safety and immunogenicity of FRSW107 as an on-demand therapy in previously treated patients with severe hemophilia A. Evaluate the on-demand treatment's PK profile of FRSW107 in previously treated patients with severe hemophilia A based on population pharmacokinetic (PopPK) methods ; preliminarily investigate the exposure-response (E-R) relationship of FRSW107 on-demand treatment in these patients if data permit.

Вмешательства

• Препарат FRSW107
  Treatment for 6 months as needed.

Первичные конечные точки

• The haemostatic effective rate [Срок оценки: 6 months]

Вторичные конечные точки (7)

• Number of infusions and IU/kg of FRSW107 needed for the treatment of bleeding episodes [Срок оценки: 6 months]
• FVIII activity during on-demand: activity recovery rate [Срок оценки: Visit1,Day1]
• Hemophilia Joint Health Score (HJHS 2.1) during on-demand treatment [Срок оценки: 6 month]
• incidence of lack of drug efficacy [Срок оценки: 6 months]
• Occurrence of AEs and SAEs [Срок оценки: 6 month]
• Incidence rate of positive FVIII inhibitors [Срок оценки: 6 month]
• Incidence rate of positive ADA, Incidence rate of positive anti-CHO antibody [Срок оценки: 6 month]

Критерии участия

Inclusive Criteria:

• Males aged 12 or younger to 65 years old.
• Patients clinically diagnosed with severe hemophilia A, i.e., those confirmed through screening or previous medical records: FⅧ Activity < 1%.
• Previous records confirm receipt of any recombinant and/or blood-derived coagulation factor VIII products or cold precipitate products, with a treatment of ≥150 exposure days (EDs ≥150).
• The participants have fully understood and been informed of this study, signed the informed consent form, and voluntarily enrolled in the clinical trial. The trial participants and/or their guardians are capable of cooperating with the hemostatic treatment and have the ability to complete all study procedures.

Критерии исключения

• Known or suspected allergy to the investigational drug or its excipients, including mouse or hamster proteins;
• Hypersensitivity or anaphylaxis after FⅧ or IgG2 injection in the past;
• FⅧ inhibitor positive (≥0.6 BU/mL) during the screening period, or have a history of FⅧ inhibitor positive in the past, or a family history of FⅧ inhibitor positive;
• Von Willebrand factor (vWF) antigen test results were lower than the lower limit of normal value;
• Severe anemia at the screening stage (hemoglobin \&lt; 60 g/L);
• Platelet count during screening period \&lt; 100×109 /L;
• Abnormal liver function:

.Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >3 times upper limit of normal (ULN); or Serum total bilirubin (TBIL) >1.5x ULN;

• Patients with abnormal renal function:

Creatinine clearance (Ccr) <50 ml/min (according to Cockcroft and Gault formula); or Serum creatinine (Cr) >1.5x ULN;

• People with active hepatitis C, that is, hepatitis C virus (HCV) antibody positive and HCV RNA positive; Or anti-treponema pallidum specific antibody (TPHA) positive; Or positive for antibodies against the human immunodeficiency virus (HIV);
• Patients with coagulation dysfunction other than hemophilia A;
• Have a medical condition that may increase the risk of bleeding;
• A history of drug or alcohol abuse;
• Have a known mental disorder that may affect trial compliance;
• Patients who have received transfusions of blood or blood components within 4 weeks prior to screening;
• Participants who had participated in other clinical trials within 1 month before screening;
• Use of any anticoagulant or antiplatelet drugs, off-label maximum dose of non-steroidal anti-inflammatory drugs (NSAID) within 7 days prior to screening; Or patients who need to be treated with anticoagulant or antiplatelet drugs or off-label maximum doses of SAID during clinical trials;
• Severe cardiovascular and cerebrovascular disease or major thromboembolic events, such as stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association \[NYHA\] grade ≥ III), and severe arrhythmias (including QTc interphase > 480 ms, corrected by Fridericia formula), uncontrolled hypertension (systolic ≥ 160 mmHg or diastolic ≥100 mmHg), deep vein thrombosis, etc.
• Study patients who had used emesezumab within 6 months prior to first administration of the drug;
• Patients who had used monoclonal antibody therapy, Fc fusion protein products (except FRSW107 and FRSW117), PEG products (except FRSW117), or intravenous immunoglobulin infusion within 3 months before the first administration of the investigational drug;
• Study patients who underwent major surgery within 3 months prior to initial drug administration (major surgery is defined in 6.2.3 Perioperative management);
• Study patients who have used FⅧ preparation of any standard half-life (e.g., Bycoch, Coproch, Biinidin, Renjie, NoL, Antaine, etc.) within 3 days or 5 half-lives prior to first administration of the drug (taking the elderly); Patients who have used any other extended half-life preparation FⅧ within 4 days or 5 half-lives prior to first dosing (for the elderly);
• Study patients with fever, severe active bacterial or viral infection, and allergies within 2 weeks before the first administration of the drug;
• Systemic immunomodulators (such as glucocorticoids \[> 10 mg/ day equivalent dose of prednisone\], alpha-interferon, immunoglobulin, cyclophosphamide, cyclosporin, etc.) used within 14 days prior to the first administration of the study drug or planned during the study period were allowed to be inhaled, nasal spray, or topical corticosteroids;
• Those who had been vaccinated within 4 weeks prior to initial administration of the study drug; Or who plan to be vaccinated during PK blood collection (only for subjects in the PK subgroup);
• Plan to have a child or sperm donation during the entire trial period and within 3 months after the last dose, or do not want to use effective physical contraception (such as condoms, diaphragms, Iuds, etc.);
• Have other serious medical conditions that the researchers said could not benefit from them
• Subjects deemed unsuitable by other investigators.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 24 центра

• Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Pe — Тяньцзинь
• Fuyang Hospital, Affiliated to Anhui Medical University — Fuyang
• Fujian Medical University Union Hospital — Фучжоу
• Ganzhou People's Hospital — Ganzhou
• Nanfang Hospital of Southern Medical University — Гуанчжоу
• Anhui Provincial Hospital — Хэфэй
• Huai'an Second People's Hospital — Huai'an
• Jinan central hospital — Цзинань
• … и ещё 16 центров

Идентификаторы

NCT: NCT07663903 · SS-107-III05

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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