An Open-Label Two-Stage Trial of the Safety, Pharmacodynamics, Biodistribution, Immunogenicity and Efficacy of Single-Dose Administration of ANB-010 in Subjects With Hemophilia A
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Biocad
- 入组人数
- 50
- 试验地点
- 34
- 主要终点
- Change in FVIII activity from baseline to Week 52
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-010 in subjects with hemophilia A. The study will have a dose-escalation design with elements of phase I/II seamless adaptive design.
详细描述
The study will be conducted in 2 stages:
Stage 1: pilot efficacy and safety study of different doses to select a potentially therapeutic dose for further study.
Stage 2: study of the efficacy and safety of ANB-010 at the selected potentially therapeutic dose.
The stage 1 design is typical of phase I clinical trials with a modified "3+3" design and dose escalation. Three subjects are to be sequentially included in each cohort, each of whom will recieved a pre-specified cohort dose of ANB-010 as a single inravenous infusion.
Subjects will be monitored for dose-limiting toxicity (DLT) events for 4 weeks after the drug infusion. The decision concerning dose escalation will be made at the Independent Data Monitoring Committee (IDMC) meetings.
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 subjects aged ≥18 years at the time of signing the informed consent form.
- •Established diagnosis of hemophilia A with a documented history of endogenous FVIII activity ≤1% AND ≤2% at screening.
- •Therapy with FVIII concentrates for at least 150 exposure days.
排除标准
- •History of use of any gene therapy product.
- •Use of emicizumab within less than 6 months before the date of signing the ICF.
- •The presence of other blood or hematopoietic disorders other than hemophilia A.
- •Presence of AAV6 antibodies detected by ELISA.
- •BMI <16 kg/m² or ≥35 kg/m².
- •Diagnosis of HIV infection.
- •HBV infection.
- •HCV infection.
- •Any active systemic infections or recurrent infections requiring systemic therapy at screening.
- •Any other disorders associated with severe immunodeficiency.
- •Relevant hepatic disorders or conditions that can be a symptom of existing liver disorder.
- •Malignancies with remission duration of less than 5 years at the time of signing the ICF, except for cured basal cell carcinoma.
结局指标
主要结局
Change in FVIII activity from baseline to Week 52
时间窗: 12 months
Assessment of ANB-010 safety
时间窗: 12 months
Proportion and characteristics of adverse events
次要结局
- Change in FVIII activity from baseline to scheduled assessment visits(12 months)
- Proportion of subjects achieving clinical response(12 months)
- Annualized consumption of FVIII concentrates by a subject(12 months)
- Annualized bleeding rate(12 months)
- Annualized rate of bleeding requiring therapy with FVIII concentrates(12 months)
- Duration of response based on activity FVIII(12 months)
- Proportion of subjects who achieved normalized response(12 months)