A Phase III Clinical Study Evaluating the Efficacy and Safety of On-demand Treatment and Perioperative Replacement Therapy With Recombinant Human Coagulation Factor VIII for Injection in Treated Severe Hemophilia A
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 12
- 主要终点
- Activity recovery
研究概览
简要总结
This study is a single arm, open, multicenter clinical trial in which the previous treated severe hemophilia A patients receive recombinant human coagulation factor VIII for injection to evaluate the efficacy and safety of on-demand treatment in the event of new bleeding events. If evaluable surgical cases occur, the overall efficacy and safety of recombinant human coagulation factor VIII for injection as a replacement therapy for severe hemophilia A PTPs during the perioperative period will be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subjects voluntarily joined this study, signed an informed consent form, and had good compliance;
- •Age (calculated from the date of signing the informed consent form): ≥12 years and ≤65 years;
- •Severe hemophilia A (coagulation factor VIII activity<1%), with exposure days (ED) of no less than 150 days prior to factor VIII (recombinant coagulation factor VIII or plasma derived coagulation factor VIII) treatment; Surgical patients need to have undergone at least 2 surgeries (including major surgeries) and plan to undergo elective surgery at the same time;
- •The subjects must be HIV negative or have a viral load of < 200 particles/μ, HIV positive patients with l or < 400000 copies/ml.
- •At baseline, no inhibitors were detected, and there was no history of Factor VIII inhibitor antibody formation (Bethesda method detection < 0.6 BU/ml, test result record required);
- •Subjects of childbearing age who agree to take effective contraceptive measures throughout the entire trial period and continue until 28 days after the last medication.
排除标准
- •Known congenital or acquired hemorrhagic diseases other than hemophilia A;
- •The subjects have used or planned to receive immunosuppressive treatments such as prednisone, cyclophosphamide, and cyclosporine in the week prior to enrollment, and are allowed to use inhaled or topical corticosteroids;
- •Those who are known or suspected to have hypersensitivity reactions to the investigational drug, including human embryonic kidney cell protein;
- •Significant liver and kidney dysfunction, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 5 upper limit of normal (ULN), and serum creatinine >1.5 ULN;
- •Hemoglobin < 60 g/L;
- •Expected to receive other drugs for the treatment of hemophilia A within 72 hours before the first administration (such as recombinant factor VIII, blood derived factor VIII, desmopressin, cryoprecipitate, plasma, etc.), or those who have used long-acting hemophilia A drugs for less than 5 half-lives before the first administration;
- •Used within 14 days before the first administration or planned to use anticoagulants or antiplatelet drugs for treatment during clinical trials;
- •Within 6 months prior to the first administration, use of Emicizumab;
- •Serious cardiovascular and cerebrovascular diseases occurring within 6 months prior to the first administration, including but not limited to cerebral hemorrhage, cerebral infarction, unstable angina, malignant arrhythmia, acute myocardial infarction, congestive heart failure (New York Heart Association cardiac function classification ≥ III), and hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure 100 mmHg) that is poorly controlled despite treatment with one or more antihypertensive drugs;
- •Participated in clinical trials of other drugs within 30 days prior to screening, or last used investigational drug with less than 5 half-lives;
- •Alcohol abuse, drug abuse, mental disorders, and intellectual disabilities.
研究组 & 干预措施
Recombinant human activated coagulation factor Ⅷ for injection
Each subject in this study receive on-demand treatment with recombinant human coagulation factor VIII for injection for 180 days, with an increase in medication frequency based on the relief after medication.
干预措施: Recombinant human activated coagulation factor VIII for injection (Drug)
结局指标
主要结局
Activity recovery
时间窗: 15 minutes after infusion
The activity of Recombinant human coagulation factor VIII measured at 15 minutes after infusion minus the baseline Recombinant human coagulation factor VIII activity divided by the expected improvement in Recombinant human coagulation factor VIII activity, which reflects the improvement in Recombinant human coagulation factor VIII levels after infusion.
The proportion of on-demand treatment improvement for newly occurring bleeding events
时间窗: For each new bleeding event, assessed within 72 hours after initial treatment
Evaluate the hemostatic efficacy of the patient after each new bleeding event (including new bleeding events during visits and new bleeding events during home treatment), and calculate the proportion of improvement as excellent+good to the total number of on-demand treatment evaluations.
次要结局
- Changes of Quality of Life Assessment before and after on-demand treatment(Up to 180 days.)
- Annualized bleeding rate (ABR)(Up to 180 days.)
- The incidence of Less Han Expected Thermal Effect(For each new bleeding event, assessed within 24 hours after initial treatment)
- The injection times of recombinant human coagulation factor VIII(Up to 180 days.)
- Changes of Haemophilia Joint Health Score before and after on-demand treatment(Up to 180 days.)
- The proportion of effective surgical hemostasis(Within 72 hours after surgery)
- The dosage of recombinant human coagulation factor VIII(Up to 180 days.)