An Open-Label, Multicenter Evaluation of Safety, Pharmacokinetics, and Efficacy of rFVIII in the Prevention and Treatment of Bleeding Episodes in Chinese With Hemophilia A
试验速览
- 阶段
- 3 期
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Recovery rate = (change actual value of rFVIII activity before and after infusion )/(change expected value of rFVIII activity before and after infusion)*100%
研究概览
简要总结
Efficacy, Safety and Pharmacokinetics Study of a rFVIII in Chinese subjects with Hemophilia A.To assess efficacy and safety of rFVIII administered as treatment and as on-demand therapy in adult and adolescent (12-65 years) patients with severe or moderately severe Hemophilia A. To determine the pharmacokinetic (PK) parameters of rFVIII.
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 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of hemophilia A
- •Age of 12 Years to 65 Years，Diagnosis of severe （defined as <1% FVIII:C documented in medical records） or moderately severe（defined as 1%-5% FVIII:C documented in medical records） hemophilia A .Subjects who（Age of 18 Years to 65 Years） have received or are currently receiving FVIII products (plasma-derived and/or recombinant FVIII) and have had >150 exposure days (EDs) with a FVIII product；The Callan (Age of 12 Years to 17) have received FVIII products and have had>50 EDs a FVIII product.
- •Subjects without a past history of, or current no factor VIII inhibitor. For laboratory-based assessments, any Bethesda inhibitor titer Lower than the laboratory's normal range or <0.6 BU/mL (BU:Bethesda Units ).
- •Liver and kidney function in accordance with the standard
- •Subjects of childbearing potential should agree to use and utilize an adequate method of contraception throughout treatment and for at least 28 days after study is stopped
- •Evidence of a personally or legally acceptable representative (legally acceptable representative is only applicable to Callan subjects) signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
- •The part one of subjects subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures; Subjects must be in a non bleeding state before the administration of rFVIII on Day 1; Subjects should not have received an infusion of any FVIII products for at least 3 days (at least 72 hours) before the administration of rFVIII on Day 1
排除标准
- •Current FVIII inhibitor or history of FVIII inhibitor (>0.6 BU/mL )
- •Diagnosed with any bleeding disorder in addition to hemophilia
- •Documented Human Immunodeficiency Virus (HIV)
- •Subjects anticipating elective surgery or other invasive procedure within 1 month following study entry
- •Treatment with an immunomodulatory within 30 days or 5 half lives preceding Day 1, whichever is longer
- •Subjects with known hypersensitivity to the active substance or to any of the excipients of rFVIII. Subjects with a known hypersensitivity to Chinese Human embryonic kidney cell proteins
- •Subjects with severe anemia requiring blood transfusion
- •Subjects with significant hepatic or renal impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 x ULN, or total bilirubin >2 x ULN or serum creatinine >2 x ULN), prothrombin time >1.5 x ULN, platelet count <80,000 μL. History of sensitivity to heparin or heparin induced thrombocytopenia or others thrombocytopenia
- •Patients with heart surgery history requires anticoagulation therapy; Subjects with severe heart disease, including myocardial infarction or heart failure Grade 3 or higher(NYHA Classification)
- •Blood pressure unable to be controlled ideally(systolic pressure>150 mmHg，diastolic pressure>90 mmHg)
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
研究组 & 干预措施
Pharmacokinetic parameters
Pharmacokinetic parameters of rFVIII measured in subset of 10 participants, consisting of:18 Years to 65 Years. In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg rFVIII preceded by a 72 hours washout period.
干预措施: Recombinant Factor VIII (50 IU/kg) (Drug)
On-demand treatment
On-demand treatment with rFVIII for 6 months age 12 Years to 65 Years. In Parts 2 of the study, subjects received repeat injections of rFVIII either as an on-demand or prophylaxis regimen at a dose and frequency determined by their study doctor.
干预措施: Recombinant Factor VIII (On-demand treatment) (Drug)
结局指标
主要结局
Recovery rate = (change actual value of rFVIII activity before and after infusion )/(change expected value of rFVIII activity before and after infusion)*100%
时间窗: At 15 and 60 minutes after the first infusion
Investigator Hemostatic Efficacy Assessment 6 Hours Post Infusion
时间窗: 6 hours post infusion
The Investigator Hemostatic Efficacy Assessment was based on a 4-point rating scale (Excellent = 1: definite pain relief or improvement in signs of bleeding, with no additional infusion, Good = 2: definite pain relief or improvement in signs of bleeding, Moderate = 3: probable or slight improvement, No Response = 4: no improvement at all between infusions).
次要结局
- The proportion of subjects who achieved the expected effect after the first infusion of the rFVIII(At 15 minutes after the first infusion)
- FVIII Maximum Plasma Concentration(Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose)
- change actual value of rFVIII activity before and after infusion levels(At 15 and 60 minutes after the first infusion)
- Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours(Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose)
- Terminal Elimination Half-Life (t1/2)(Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose)
- Time to Reach Maximum Observed Plasma Concentration(Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose)