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 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.
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 (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.
