An Open-label, Non-comparative, Single Dose-Escalation Study of the Safety, Pharmacodynamics and Efficacy of ANB-002 in Patients With Hemophilia B
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Biocad
- 入组人数
- 28
- 试验地点
- 34
- 主要终点
- Change in FIX activity from baseline
研究概览
简要总结
The goal of this multicenter, two-stage, open-label study is to investigate the safety, immunogenicity, and efficacy of ANB-002 in subjects with hemophilia В. The study will have a dose-escalation design with elements of phase I/II seamless adaptive design.
详细描述
The study design includes ANB-002 dose escalation in at three cohorts. In Cohort 1, the subject is treated with a single dose of ANB-002 (dose 1) administered as an intravenous infusion. Follow-up for the assessment of dose-limiting toxicity (DLT) will be carried out for 28 days. If no DLT events are observed in the subject of Cohort 1, the following subjects will be included in Cohort 1.
In Cohort 2, the subjects are treated with a single dose of ANB-002 (dose 2). In Cohort 3, the subject are treated with a single dose of ANB-002 (dose 3).
The decision to continue enrolling in cohorts will be made at the Independent Data Monitoring Committee (IDMC) meeting. After the IDMC makes a decision regarding the dosing subjects, further enrolment to the cohort will be carried out.
Based on the data from the follow-up period of subjects included in Сohorts 1-3, a potential therapeutic dose for further study will be determined and additional patients will be included to recieve this dose.
In exploratory Cohort 4 patients with anti-AAV5 antibodies and/or hepatitis B in anamnesis will be included. These subjects will recieve the dose 3 of ANB-002.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male with hemophilia B.
- •Age ≥18 years.
- •FIX activity at screening ≤2% without FIX inhibitor.
- •≥150 previous exposure days of treatment with FIX concentrates.
排除标准
- •Previous gene therapy.
- •Other blood or hematopoietic disorders.
- •Positive Anti-AAV5 antibodies (for Cohorts 1-3).
- •Diagnosed HIV-infection, not controlled with anti-viral therapy.
- •Hepatitis B (for Cohorts 1-3), acute or chronic hepatitis C.
- •Any active systemic infections or recurrent infections requiring systemic therapy at screening.
- •Any other disorders associated with severe immunodeficiency.
- •Significant hepatic disorders (liver cirrhosis, liver fibrosis, etc).
- •Malignancies with remission <5 years.
结局指标
主要结局
Change in FIX activity from baseline
时间窗: 12 months; final assessment - 5 years
Proportion of subjects with adverse reactions
时间窗: 12 months; final assessment - 5 years
次要结局
- Annualized rate of bleedings requiring therapy with FIX concentrates(5 years)
- Annualized use of FIX concentrates(5 years)
- Changes in EuroQol-5D-3L (European Quality of Life Questionnaire) scores from baseline(5 years)
- Changes in FIX activity(5 years)
- Annualized bleeding rate(5 years)
- Changes in Haemo-A-QoL (Hemophilia-Specific Quality of Life) scores from baseline(5 years)
- Changes in SF-36 (Short Form-36) scores from baseline(5 years)
- Response duration based on FIX activity(5 years)
- Evaluation of the condition of joints based on the Hemophilia Joint Health Score (HJHS)(5 years)