NCT04565236已完成4 期
A Post Approval Commitment Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of KOVALTRY in Chinese Children, Adolescents /Adults With Severe Hemophilia A
适应症
干预措施
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 45
- 试验地点
- 10
- 主要终点
- Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part A
研究概览
简要总结
The goal of this study is to gather more information on safety and efficacy of Kovaltry for the prevention and treatment of bleeds in Chinese children, adolescents/adults with severe hemophilia A. In addition, pharmacokinetic parameters of Kovaltry will be assessed in a subset of patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Part A (PTPs):
- •Chinese participants with severe hemophilia A (defined as Factor VIII (FVIII): C < 1% with one- stage clotting assay documented at the time of screening)
- •Currently receiving on-demand or any type of prophylaxis treatment regimen with any FVIII product
- •For participants < 12 years of age, ≥ 50 exposure days (ED); for participants ≥ 12 to 65 years of age, ≥ 150 ED with any FVIII product
- •No current evidence of inhibitor
- •No history of FVIII inhibitor formation
- •Signed informed consent
- •Part B (PUPs/MTPs):
- •Participants must be <6 years of age at the time of their parent or legal representative's signature of informed consent on the participant's behalf
- •Chinese participants with severe hemophilia A (defined as Factor VIII (FVIII): C < 1% with one- stage clotting assay documented at the time of screening)
- •PUPs must have no previous exposure to any FVIII product. MTPs must have no more than 1 ED with any purified FVIII concentrate or 3 exposures with FFP or cryoprecipitate.
- •MTPs must have no current evidence of inhibitor antibody as measured by the Nijmegen-modified Bethesda assay (<0.6 BU/mL) in 2 consecutive samples and must have absence of clinical signs or symptoms of decreased response to FVIII administration. Testing for the 2 negative samples must be performed by the central laboratory at least 1 week but not more than 2 weeks apart. Participants may not receive FVIII product within 72 hours prior to the collection of samples for inhibitor testing.
- •PUPs and MTPs must observe a 6-month washout period if they have received subcutaneous factor substitution therapy (emicizumab).
- •PUPs may be included if they will receive their first FVIII dose with KOVALTRY for treatment of first bleed and agree to start prophylaxis as part of their care. MTPs may be included if they agree to start prophylaxis as part of their care.
排除标准
- •Part A (PTPs):
- •Any other bleeding disease that is different from hemophilia A (e.g. von Willebrand disease, hemophilia B)
- •Platelet count < 100 000/mm^3
- •Impaired renal function (serum creatinine > 2.0 mg/dL) or active liver disease (alanine aminotransferase/aspartate aminotransferase [ALT/AST] > 5x ULN)
- •Human immunodeficiency virus (HIV) positive with an absolute CD4 lymphocyte cell count < 250 cells/μL
- •Known hypersensitivity to the active substance, mouse or hamster protein
- •Receiving chemotherapy, immune modulatory drugs other than anti-retroviral chemotherapy, or chronic use of oral or intravenous (IV) corticosteroids (> 14 days) within the last 3 months.
- •Requiring any pre-medication to tolerate FVIII infusions (e.g. antihistamines)
- •Currently participating in another investigational drug study, or having previously participated in a clinical study involving an investigational drug within 30 days of signing informed consent or participated in completed interventional clinical studies with BAY81-8973 (Kovaltry)
- •Planned major surgery, defined as surgery with respiratory assistance and/or general anesthesia
- •Part B (PUPs/MTPs):
- •Any other bleeding disease that is different from hemophilia A (e.g. von Willebrand disease, hemophilia B)
- •Platelet count < 100 000/mm^3
- •Impaired renal function (serum creatinine >2× upper limit of normal [ULN]) or active liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >5× ULN) based on screening laboratory assessments
- •MTPs with history of FVIII inhibitor formation
- •Known hypersensitivity to the active substance, mouse or hamster protein
- •First treatment with KOVALTRY for high risk bleeding situations (e.g., surgery, intracranial bleed) or requiring intensive or prolonged treatment
- •Receiving chemotherapy, immune modulatory drugs other than anti-retroviral chemotherapy, or chronic use of oral or intravenous (IV) corticosteroids (> 14 days) within the last 3 months.
- •Requiring any pre-medication to tolerate FVIII infusions (e.g. antihistamines)
- •Currently participating in another investigational drug study, or having previously participated in a clinical study involving an investigational drug within 30 days of signing informed consent or participated in completed interventional clinical studies with BAY 81-8973 (Kovaltry)
- •Planned major surgery, defined as surgery with respiratory assistance and/or general anesthesia
- •Unable to tolerate volume of blood draws required for study participation
研究组 & 干预措施
Part A: PTPs <12 years of age
Experimental
Previously treated severe hemophilia A patients (PTPs) <12 years of age
干预措施: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 1 (Biological)
Part A: PTPs ≥12 to 65 years of age
Experimental
Previously treated severe hemophilia A patients (PTPs) ≥12 to 65 years of age
干预措施: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 2 (Biological)
Part B: PUPs/MTPs <6 years of age
Experimental
Previously untreated/minimally treated severe hemophilia A patients (PUPs/MTPs) <6 years of age
干预措施: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 3 (Biological)
结局指标
主要结局
Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part A
时间窗: Up to 6 months
Annualized number (mean +/- standard deviation) of all bleeding episodes that occurred during the prophylaxis treatment period is reported for previously treated patients (PTPs). All bleeding episodes: sum of spontaneous bleeds and trauma bleeds exclude bleeding due to surgery.
Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part B
时间窗: Up to 48 hours post-infusion during 6 months
Annualized number (mean +/- standard deviation) of all bleeding episodes that occurred within 48 hours of previous prophylaxis infusion is reported for previously untreated/minimally treated patients (PUPs/MTPs). All bleeding episodes: sum of spontaneous bleeds and trauma bleeds exclude bleeding due to surgery.
次要结局
- Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part A(Up to 48 hours post-infusion during 6 months)
- Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part B(Up to 51 exposure days)
- Number of Infusions Per Bleeding Episode(Part A: up to 6 months; Part B: up to 51 exposure days)
- Number of Surgeries Per Physician's Assessment of Adequacy of Hemostasis in Minor Surgery(Part A: up to 6 months; Part B: up to 51 exposure days)
- FVIII In-vivo Recovery in Part B(At baseline, Visit 6 (ED 20), unscheduled visit and final visit, up to 51 exposure days)
- Factor VIII Inhibitor Development by the Nijmegen Bethesda Assay(Part A: up to 6 months; Part B: up to 51 exposure days)
- Number of Participants With Treatment-emergent Adverse Events(Part A: up to 6 months; Part B: up to 51 exposure days)
- FVIII In-vivo Recovery in Part A(At baseline, Month 2 and final visit, up to 6 months)
- Maximum Observed Concentration of FVIII in Plasma (Cmax) in Part A(at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years)
- Area Under the Plasma Concentration of FVIII Versus Time Curve From Zero to Infinity (AUC) in Part A(at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years)
- Half-life (t1/2) of FVIII in Plasma in Part A(at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years)
研究者
研究点 (10)
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