A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors to Factor VIII or IX
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 23
- 主要终点
- Proportion of Successfully Treated Mild/Moderate Bleeding Episodes
研究概览
简要总结
The purpose of the study is to assess the safety, efficacy and pharmacokinetics of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX
详细描述
This was a global, multicenter, Phase III, prospective, open-label, randomized, crossover study. After obtaining informed consent and performance of screening procedures, patients who met all inclusion and exclusion criteria were randomized to one of two treatment regimens as follows:
- 75 µg/kg treatment regimen
- 225 µg/kg treatment regimen
For each treatment regimen there were two phases:
- Phase A (Initial phase)
- Phase B (Treatment phase)
The assigned treatment regimen was the dose administered in Phase A and was the starting dose in Phase B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •be male with a diagnosis of congenital hemophilia A and/or B of any severity
- •have one of the following:
- •a positive inhibitor test Bethesda Unit (BU) ≥ 5 (as confirmed at screening by the institutional lab), OR
- •a BU<5 but expected to have a high anamnestic response to FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings, OR
- •a BU<5 but expected to be refractory to increased dosing of FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings
- •be 12 years or older, up to and including 75 years of age (NOTE: different age restrictions may apply per local regulation and/or ethical considerations)
- •have at least 3 bleeding episodes of any severity in the past 6 months be capable of understanding and willing to comply with the conditions of the protocol
- •have read, understood and provided written informed consent (patient and/or parent(s)/legal guardian(s) if <18 years of age)
排除标准
- •have any coagulation disorder other than hemophilia A or B
- •be immuno-suppressed (i.e., the patient should not be receiving systemic immunosuppressive medication, cluster of differentiation 4 (CD4) counts at screening should be >200/µl)
- •have a known allergy or hypersensitivity to rabbits
- •have platelet count <100,000/mL
- •have had within one month prior to first administration of the study drug in this study a major surgical procedure (e.g. orthopedic, abdominal)
- •have received an investigational drug within 30 days of the first study drug administration, or is expected to receive such drug during participation in this study
- •have a clinically relevant hepatic (AST and/or alanine aminotransferase (ALT) >3 times the upper limit of normal) and/or renal impairment (creatinine >2 times the upper limit of normal)
- •have a history of arterial and/or venous thromboembolic events (such as myocardial infarction, ischemic strokes, transient ischemic attacks, deep venous thrombosis or pulmonary embolism) within 2 years prior to first dose of study drug, or current New York Heart Association (NYHA) functional classification score of stage II -IV
- •have an active malignancy (those with non-melanoma skin cancer are allowed)
- •have any life-threatening disease or other disease or condition which, according to the investigator's judgment, could imply a potential hazard to the patient, interfere with the trial participation or trial outcome (e.g., a history of non-responsiveness to bypassing products).
结局指标
主要结局
Proportion of Successfully Treated Mild/Moderate Bleeding Episodes
时间窗: 12 hours after first administration of study drug
For the primary efficacy endpoint, successful treatment of a bleeding episode was defined as a combination of the following: * "Good" or "Excellent" response noted by the patient * Study drug treatment: No further treatment with study drug beyond timepoint for this bleeding episode * No other hemostatic treatment needed for this bleeding episode * No administration of blood products that would indicate continuation of bleeding beyond timepoint * No increase of pain beyond timepoint that could not otherwise be explained
次要结局
- Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode(Through study completion)
- Proportion of Mild/Moderate Bleeding Episodes With Patient (Pt)-Reported "Good" or "Excellent" Responses at 12 Hours(at 12 hours)
- Time to Assessment of a "Good" or "Excellent" Response of Mild/Moderate Bleeding Episodes by the Patient(Within 24 hours of Bleeding Episode)
- Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode(Within 24 hours of Bleeding Episode)