Hemophilia B
Conditions
Brief summary
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.
Detailed 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.
Interventions
GENETICANB-002, dose 1
Adeno-associated viral vector carrying the FIX gene single infusion at dose 1.
GENETICANB-002, dose 2
Adeno-associated viral vector carrying the FIX gene single infusion at dose 2.
GENETICANB-002, dose 3
Adeno-associated viral vector carrying the FIX gene single infusion at dose 3.
Sponsors
Biocad
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male with hemophilia B. 2. Age ≥18 years. 3. FIX activity at screening ≤2% without FIX inhibitor. 4. ≥150 previous exposure days of treatment with FIX concentrates.
Exclusion criteria
1. Previous gene therapy. 2. Other blood or hematopoietic disorders. 3. Positive Anti-AAV5 antibodies (for Cohorts 1-3). 4. Diagnosed HIV-infection, not controlled with anti-viral therapy. 5. Hepatitis B (for Cohorts 1-3), acute or chronic hepatitis C. 6. Any active systemic infections or recurrent infections requiring systemic therapy at screening. 7. Any other disorders associated with severe immunodeficiency. 8. Significant hepatic disorders (liver cirrhosis, liver fibrosis, etc). 9. Malignancies with remission \<5 years.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in FIX activity from baseline | 12 months; final assessment - 5 years |
| Proportion of subjects with adverse reactions | 12 months; final assessment - 5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized bleeding rate | 5 years | — |
| Annualized rate of bleedings requiring therapy with FIX concentrates | 5 years | — |
| Changes in Haemo-A-QoL (Hemophilia-Specific Quality of Life) scores from baseline | 5 years | Haemo-A-QoL is a quality of life (QoL) assessment instrument for patients with haemophilia, including the domains of consequences of bleeding, emotional impact, physical functioning, role functioning, treatment concern, and worry. Using scale overall score ranges from 0 to 100.The high score represent low quality of life. |
| Changes in FIX activity | 5 years | — |
| Changes in SF-36 (Short Form-36) scores from baseline | 5 years | SF-36 is a questionnaire for evaluating health-related QoL (Quality of Life). The 36 questions are meant to reflect 8 domains of health, including physical functioning, physical role, pain, general health, vitality, social function, emotional role, and mental health. SF-3 overall score ranges from 0 to 100. The lower the score the more disability. |
| Response duration based on FIX activity | 5 years | — |
| Evaluation of the condition of joints based on the Hemophilia Joint Health Score (HJHS) | 5 years | Hemophilia Joint Health Score (HJHS) is the assessment system of joints in patients with haemophilia. Each joint (knee, elbow and ankle) receives a numeric score, which can be compared to itself over time to determine whether a joint is showing degeneration. The maximum score for an individual index joint is 20. Gait is scored 0 to 4. The maximum HJHS total score is 124, with a higher score indicating worse joint health. |
| Changes in EuroQol-5D-3L (European Quality of Life Questionnaire) scores from baseline | 5 years | The EQ-5D-5L descriptive system of health-related QoL states consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). The EQ-5D-5L VAS overall score ranges from 0 to 100. A higher score is considered to be more favorable. |
| Annualized use of FIX concentrates | 5 years | — |
Countries
Belarus, Russia
Contacts
Primary ContactAnna Eremeeva, MD PhD
Outcome results
None listed