NCT02210091已完成3 期
A Phase 3 Prospective, Uncontrolled, Multicenter Study Evaluating Pharmacokinetics, Efficacy, Safety, and Immunogenicity of BAX 855 (PEGylated Full-length Recombinant FVIII) in Previously Treated Pediatric Patients With Severe Hemophilia A
Baxalta now part of Shire74 个研究点 分布在 11 个国家目标入组 75 人开始时间: 2014年10月31日最近更新:
适应症
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 75
- 试验地点
- 74
- 主要终点
- Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)
研究概览
简要总结
The study purpose is:
- To assess the incidence of FVIII inhibitory antibodies during 6 months of twice weekly prophylactic treatment with BAX 855 or 50 exposure days (EDs), whichever occurs last.
- To compare pharmacokinetic (PK) parameters to ADVATE.
- To assess hemostatic efficacy in prophylaxis and the treatment of bleeding episodes.
- To evaluate safety and immunogenicity.
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
- — 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Severe hemophilia A (Factor VIII (FVIII) <1%) determined by central laboratory.
- •<12 years old at the time of screening.
- •Participants aged ≥6 to <12 years of age have been previously treated with plasma-derived and/or recombinant Factor VIII (rFVIII) concentrate(s) for a minimum of 150 exposure days (EDs) (based on the participant's medical records).
- •Participants <6 years of age have been previously treated with plasma-derived and/or rFVIII concentrate(s) for at least 50 EDs (based on the participant's medical records).
- •Participant is human immunodeficiency virus (HIV) negative; or HIV positive with stable disease and CD4+ count of ≥200 cells/mm^3, as confirmed by central laboratory.
- •Participant and/or legal representative accepts prophylactic treatment over a period of 6 months.
- •Participant and/or the legal representative is willing and able to comply with the requirements of the protocol.
排除标准
- •Participant has detectable FVIII inhibitory antibodies (≥0.4 Bethesda Units (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
- •Participant has a history of FVIII inhibitory antibodies (≥0.4 BU using the Nijmegen modification of the Bethesda assay or ≥0.6 BU using the Bethesda assay) at any time prior to screening.
- •Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG), or Tween
- •Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
- •Participant's platelet count is <100,000/μL.
- •Participant has severe chronic hepatic dysfunction (eg, ≥5 times upper limit of normal (ULN) alanine aminotransferase (ALT), as confirmed by central laboratory at screening, or a documented international normalized ratio (INR) >1.5).
- •Participant has severe renal impairment (serum creatinine >1.5 times ULN).
- •Participant is scheduled to receive during the course of the study, an immunomodulating drug (eg, corticosteroid agents at a dose equivalent to hydrocortisone >10 mg/day, or α-interferon) other than anti-retroviral chemotherapy.
- •Participant has current or recent (<30 days) use of other PEGylated drugs prior to study participation or is scheduled to use such drugs during study participation.
- •Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
- •Participant has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the Investigator, would affect participant safety or compliance.
- •Participant's legal representative is a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study.
结局指标
主要结局
Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)
时间窗: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
Inhibitory antibodies to FVIII were measured using the Nijmegen modification of the Bethesda assay. Incidence of an FVIII inhibitory antibody was defined as an inhibitor level ≥0.6 Bethesda units \[BU\].
次要结局
- Annualized Bleeding Rate (ABR)(During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last)
- Consumption of BAX 855: Number of Prophylactic Infusions Per Month Per Participant(During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last)
- Consumption of BAX 855: Number of Prophylactic Infusions Per Year (Annualized) Per Participant(During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last)
- Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Month Per Participant(During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last)
- Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Year (Annualized) Per Participant(During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last)
- Consumption of BAX 855: Number of Infusions Per Bleeding Episode(During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last)
- Consumption of BAX 855: Weight-adjusted Dose Per Bleeding Episode(During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last)
- Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed(After first exposure to BAX 855 until completion of study - approx. 6 months per participant.)
- Serious Adverse Events (SAEs) Possibly or Probably Related to BAX 855(After first exposure to BAX 855 until completion of study - approx. 6 months per participant.)
- Non-serious Adverse Events Possibly or Probably Related to BAX 855(After first exposure to BAX 855 until completion of study - approx. 6 months per participant.)
- Number of Participants With Clinically Significant Changes in Vital Signs(After first exposure to BAX 855 until completion of study - approx. 6 months per participant.)
- Number of Clinically Significant Changes in Clinical Laboratory Parameters (Hematology, Clinical Chemistry, Lipids)(After first exposure to BAX 855 until completion of study - approx. 6 months per participant.)
- Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins(After first exposure to BAX 855 until completion of study - approx. 6 months per participant.)
- Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion (AUC0-∞)((1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4)
- Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion Per Dose, (AUC0-∞/Dose)((1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4)
- Pharmacokinetics (PK): Mean Residence Time (MRT)((1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4)
- Pharmacokinetics (PK): Clearance (CL)((1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4)
- Pharmacokinetics (PK): Plasma Half-life (T1/2)((1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4)
- Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)((1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4)
- Pharmacokinetics (PK): Incremental Recovery (IR)((1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4)
- Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay(Baseline, Week 5 (or 10-15 EDs, whichever occurs last), Week 12, and Month 6 (Completion/Termination))
- Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay(Baseline, Week 5 (or 10-15 Exposure Days [EDs], whichever occurs last), Week 12, and Month 6 (Completion/Termination))
研究者
研究点 (74)
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