An Open-Label, Multicenter Evaluation of the Safety and Efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) in Adolescent and Adult Patients With Hemophilia A.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 119
- 试验地点
- 17
- 主要终点
- Part A - score of bleeding symptoms and Vital signs.
研究概览
简要总结
The primary objectives of the study are to evaluate the efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) in the Prevention and Treatment of Bleeding in patients with hemophilia A.
The secondary objectives are to evaluate the efficacy and safety of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) in the prevention and treatment of bleeding episodes, to investigate the quality of life in patients who used the FRSW107.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 60 Years（Child, Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male, aged 12 to 60 years
- •Severe hemophilia A. The activity of the coagulation factor VIII (FVIII:C) < 1%, and previously treated with FVIII concentrate (s) for a minimum of 150 exposure days (EDs) prior to study entry.
- •No history of a positive inhibitor test (< 0.6 BU) or clinical signs of decreased response to FVIII administrations within 2 years before the test or during the screening period. No Family history of inhibitors.
- •Non-immune deficiency, with a certain immune capacity (CD4 > 200/μL)
- •Platelet count > 100,000 platelets/μL.
- •Normal prothrombin time or INR < 1.
- •Normal previous results of vWF antigen examination.
- •Negative lupus anticoagulant.
- •the patient has a detailed record of bleeding events for at least 6 months (the subject can be admitted to the on-demand treatment group with spontaneous bleeding ≥3 times within 6 months).
- •Capable of understanding and willing to comply with the conditions of the protocol have read (patient and/or guardian).
排除标准
- •Hypersensitive to any of the excipients of the test materials (e.g. allergic to murine or hamster origin heterologous proteins).
- •History of hypersensitivity or anaphylaxis associated with any FVIII or II immunoglobulin administration.
- •Other coagulation disorder(s) in addition to hemophilia A.
- •Patients with severe heart disease, including myocardial infarction, heart failure (III or higher level).
- •Clinically significant of other systematic diseases: alcoholism, drug abuse, mental disorders and mental retardation.
- •Significant hepatic or renal impairment (ALT and AST > 2×ULN; serum bilirubin level > 3 × upper limit of normal (ULN), BUN > 2×ULN, Cr > 176.8µmol/L).
- •Patients who received any anticoagulant or antiplatelet therapy within one week prior screening or need to receive an anticoagulant or antiplatelet therapy during the period of clinical trials.
- •Patients having major surgery or receiving blood or blood components transfusion within 4 weeks prior screening or having planned major surgery schedule during the study.
- •Patients who previously participated in the other clinical trials within 1 month prior screening.
- •One or more clinically significant tests for Hepatitis B Virus Surface Antigen, Human Immunodeficiency Virus (HIV), Antisyphilitic spirulina (TPHA) and Hepatitis C Virus (HCV) Antibody.
- •Any life-threatening disease or condition which, according to the investigator's judgment, could not benefit from the trial participation.
- •Patient who is considered by the other investigators not suitable for clinical study.
- •NOTE:Other protocol-defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Arm 1-on demand treatment
Part A-Participants will receive on-demand treatment with Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection for 6 months.
干预措施: Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (Drug)
Arm 2- prophylaxis treatment
Part B-Participants will receive prophylaxis treatment with Recombinant Human Coagulation Factor VIII-Fc fusion for 6 months.
12 Participants of them will receive PK assessment at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.)，measured by one-stage assay, they would not be given prophylaxis treatment until the completion of PK blood collection.
干预措施: Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (Drug)
结局指标
主要结局
Part A - score of bleeding symptoms and Vital signs.
时间窗: For the duration of study participation, 6 months.
Response to treatment with rFVIIIFc for bleeding episodes, using the 4-point bleeding response scale.
Part B- Annualized Bleeding Rates(ABR).
时间窗: For the duration of study participation, 6 months.
Annualized bleeding rate = (number of bleeding episodes during the efficacy, period/total number of days during the efficacy period)\*365.25. The efficacy period begins with the first prophylactic dose of FRSW107 and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. Any injection to treat the bleeding episode taken more than 72 hours after the preceding one was considered the first injection to treat a new bleeding episode at the same location. Any bleeding at a different location was considered a separate bleeding episode, regardless of time from last injection.
Part B-Number of target joints.
时间窗: For the duration of study participation, 6 months.
The joint with ≥3 times of spontaneous bleeding in 6 consecutive months is the target joint, while the joint with \< 2 times of bleeding in 12 consecutive months is no longer the target joint.
次要结局
- Part B-Half-life (t½) as Measured by aPTT Clotting Assay(Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).)
- Part B-Clearance (CL) as Measured by the aPTT Clotting Assay(Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).)
- Part B-Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay.(Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).)
- Part B -Number of injections required to resolve a bleeding episode.(For the duration of study participation, 6 months.)
- Part B -Quality of life assessment.(For the duration of study participation, 6 months.)
- Part B -Number of participants with inhibitor development(6 months and at least 50 exposure days.)
- Part B-Time of Cmax (Tmax) as Measured by aPTT Clotting Assay.(Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).)
- Part A -Number of injections required to resolve a bleeding episode.(For the duration of study participation, 6 months.)
- Part A -Quality of life assessment.(For the duration of study participation, 6 months.)
- Part A-rFVIIIFc incremental recovery (IR).(For the duration of study participation, 6 months.)
- Part A -Total Dose Required for Resolution of a Bleeding Episode.(For the duration of study participation, 6 months.)
- Part B - Number of Participants With Incidence of Antibody Formation to CHINESE HAMSTER OVARY (CHO).(before and the duration of study participation, 6 months.)
- Part B -Number of All Bleeds.(before and the duration of study participation, 6 months.)
- Part B-Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay(Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).)
- Part B-Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay.(Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).)
- Part B-Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay.(Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).)