Overview
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.
Description
The study design includes ANB-002 dose escalation in at least two cohorts. In Cohort 1, the subject treated with a single dose of ANB-002 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.
The decision to continue enrolling in Cohort 1 or dosing in Cohort 2 subjects will be made at the Independent Data Monitoring Committee (IDMC) meeting. After the IDMC makes a decision regarding the dosing in Cohort 2 subjects, further enrolment to the cohort will be carried out according to the following principles described above.
Based on the data from the follow-up period of subjects included in Сohorts 1 and 2, a potential therapeutic dose for further study will be determined. The total duration of participation of one subjects in the study will be 5 years.
Eligibility
Inclusion Criteria:
- Male with hemophilia B.
- Age ≥18 years.
- FIX activity at screening ≤2% without FIX inhibitor.
- ≥150 previous exposure days of treatment with FIX concentrates.
Exclusion Criteria:
- Previous gene therapy.
- Other blood or hematopoietic disorders.
- Positive Anti-AAV5 antibodies.
- Diagnosed HIV-infection, not controlled with anti-viral therapy.
- Hepatitis B, 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.