NCT03855280已完成3 期
Evaluation of a Recombinant Factor IX Product, APVO101, in Previously-Treated Pediatric Patients With Hemophilia B
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 11
- 主要终点
- Annualized Bleeding Rate (ABR) Overall
研究概览
简要总结
Phase 3/4, single arm, open-label study to evaluate PK, safety, and efficacy of APVO101 prophylaxis in severe or moderately severe hemophilia B subjects < 12 years of age.
详细描述
Study APVO101-903 is a Phase 3/4, single arm, open-label clinical trial. The purpose of the study is to evaluate pharmacokinetics (PK), safety, and efficacy of APVO101 prophylaxis in severe or moderately severe hemophilia B subjects < 12 years of age. The study is designed to gather information in two age groups of previously treated (with a minimum of 50 previous ED to factor IX replacement therapy) pediatric patients, specifically those < 6 years of age and 6 to <12 years of age.
Study APVO101-903 consists of three distinct phases:
- PK Phase - PK evaluation will consist of administration of a single 75 ± 5 IU/kg dose, followed by factor IX activity and safety assessments up to 50 hours post-infusion.
- Treatment Phase - subjects will receive APVO101 prophylaxis (starting prophylaxis dose to be determined based on APVO101 recovery; ideally within the recommended dose range: 35 - 75 IU/kg; twice weekly) for 50 ED (approximately 6 months).
- Continuation Phase - subjects may continue to receive APVO101 prophylaxis (recommended dose range: 35 - 75 IU/kg; twice weekly) for an additional ≥ 50 ED.
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
- — 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: < 11.5 years of age at the time of the first dose and < 12 years throughout the Treatment Phase of the study (for at least 50 ED).
- •Informed consent: subject's parent or legal guardian written Institutional Review Board (IRB)/Ethics Committee (EC)-approved informed consent. An assent form (IRB/EC-approved) will be obtained, when required by local regulations/guidelines.
- •Willingness and ability to make the required study visits, and follow instructions while enrolled in the study (for at least 50 ED; approximately 6 months).
- •Documented severe or moderately severe hemophilia B diagnosis (factor IX activity ≤ 2 IU/dL); in addition, severity may be indicated by the occurrence of one or more joint bleeding episode(s) at any point in the child's medical history requiring infusion(s) to replace factor IX.
- •Subjects must be on prophylaxis or switch to a prophylaxis regimen for the duration of the study.
- •Previously treated patients with a minimum of 50 ED (as documented and determined by the investigator) to a preparation/blood components containing factor IX.
- •Willingness to adhere to the 4-day washout period of any factor IX replacement therapy prior to PK evaluation. In case of previous exposure to a factor IX product with a prolonged half-life, a washout period of 3 half-lives is required in order to achieve steady state factor IX level prior to exposure to APVO
- •Immunocompetent (CD4 count > 400/mm3) and not receiving immune modulating or chemotherapeutic agents.
- •Platelet count at least 150,000/mm
- •Liver function: alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2 times the upper limit of the normal range.
- •Total bilirubin ≤ 1.5 times the upper limit of the normal range.
- •Renal function: serum creatinine ≤ 1.25 times the upper limit of the normal range.
- •Hemoglobin ≥ 7 g/dL.
排除标准
- •History of factor IX inhibitor ≥ 0.6 Bethesda Units (BU); confirmed by the screening result.
- •Existence of another coagulation disorder.
- •Evidence of thrombotic disease, fibrinolysis, or disseminated intravascular coagulation (DIC).
- •Use of an investigational drug within 30 days prior to study entry.
- •Previous use of APVO
- •Use of medications that could impact hemostasis, such as aspirin.
- •Known hypersensitivity to the active substance or to any of the excipients in the investigational products.
- •Known allergic reaction to hamster proteins.
- •History of poor compliance, geographic isolation, unreliable transportation, a serious medical or social condition, or any other circumstance that, in the opinion of the investigator, would interfere with participation or compliance with the study protocol.
- •History of adverse reaction to either plasma-derived factor IX or recombinant factor IX that interfered with the subject's ability to treat bleeding episodes with a factor IX product.
- •History of any medical condition that would impact the efficacy evaluation and/or safety evaluation of the study product.
研究组 & 干预措施
APVO101
Experimental
APVO101: 35 - 75 IU/kg; twice weekly
干预措施: APVO101 (Drug)
结局指标
主要结局
Annualized Bleeding Rate (ABR) Overall
时间窗: Exposure Day 1 through study completion (up to 2.5 years)
The primary efficacy variable was the ABR while on prophylaxis to prevent bleeding episodes. The ABR was defined as the number of bleeding episodes per year.
Annualized Bleeding Rate (ABR)
时间窗: Exposure Day 1 up to 50 exposure days (approximately 6 months)
The primary efficacy variable was the ABR while on prophylaxis to prevent bleeding episodes. The ABR was defined as the number of bleeding episodes per year.
次要结局
- Volume of Distribution at Steady-State (Vdss)(Pre-infusion to 50 hours post-infusion)
- Subject Rating of APVO101 Efficacy - Evaluated at the Bleeding Episode Level (Overall)(Exposure Day 1 through study completion (up to 2.5 years))
- Investigator Rating of APVO101 Prophylaxis Efficacy (Overall)(Exposure Day 1 through study completion (up to 2.5 years))
- Investigator Rating of APVO101 Efficacy for Control and Management of Bleeding Episodes (Treatment Phase)(Exposure Day 1 up to 50 exposure days (approximately 6 months))
- Concentration (Cmax)(Pre-infusion to 50 hours post-infusion)
- Terminal Half-Life (t 1/2)(Pre-infusion to 50 hours post-infusion)
- Incremental Recovery (IR)(Pre-infusion to 50 hours post-infusion)
- Investigator Rating of APVO101 Prophylaxis Efficacy (Treatment Phase)(Exposure Day 1 up to 50 exposure days (approximately 6 months))
- Investigator Rating of APVO101 Efficacy for Control and Management of Bleeding Episodes (Overall)(Exposure Day 1 through study completion (up to 2.5 years))
- Area Under the Curve (0-inf)(Pre-infusion to 50 hours post-infusion)
- Mean Residence Time (MRT)(Pre-infusion to 50 hours post-infusion)
- Clearance (CL)(Pre-infusion to 50 hours post-infusion)
- Subject Rating of APVO101 Efficacy - Evaluated at the Bleeding Episode Level (Treatment Phase)(Exposure Day 1 up to 50 exposure days (approximately 6 months))
研究者
研究点 (11)
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