Study of the Safety, Pharmacodynamics and Efficacy of ANB-002 in Patients With Hemophilia B (SAFRAN)
- Conditions
- Hemophilia B
- Interventions
- Genetic: ANB-002, dose 1Genetic: ANB-002, dose 2
- Registration Number
- NCT06120582
- Lead Sponsor
- Biocad
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 28
- Male with hemophilia B.
- Age ≥18 years.
- FIX activity at screening ≤2% without FIX inhibitor.
- ≥150 previous exposure days of treatment with FIX concentrates.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 ANB-002, dose 1 Subjects in Cohort 1 will receive ANB-002 at a dose 1. 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. Cohort 2 ANB-002, dose 2 Subjects in Cohort 2 will receive ANB-002 at a dose 2. The decision to continue enrolling in Cohort 1 or dosing in Cohort 2 subjects will be made at the IDMC meeting. After the IDMC makes a decision regarding the dosing in Cohort 2 subjects, the next subject will be included in Cohort 2. If no DLT events are observed in the subject of Cohort 2, the following subjects will be included in Cohort 2.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Changes in FIX activity 5 years Annualized bleeding rate 5 years Annualized use of FIX concentrates 5 years Annualized rate of bleedings requiring therapy with FIX concentrates 5 years 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.
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 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.
Trial Locations
- Locations (17)
Republican Scientific and Practical Center for Radiation Medicine and Human Ecology
🇧🇾Gomel, Belarus
Federal Budgetary Institution "Moscow City Clinical Hospital named after S. P. Botkin"
🇷🇺Moscow, Russian Federation
LLC "Medis"
🇷🇺Nizhny Novgorod, Russian Federation
State Novosibirsk Regional Clinical Hospital
🇷🇺Novosibirsk, Russian Federation
Russian Research Institute of Hematology and Transfusiology Federal State Institution of Federal Medical and Biological Agency
🇷🇺Saint Petersburg, Russian Federation
City Polyclinic №37
🇷🇺Saint Petersburg, Russian Federation
Almazov National Medical Research Centre
🇷🇺Saint Petersburg, Russian Federation
Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Healthcare of the Russian Federation
🇷🇺Samara, Russian Federation
State Institution "Komi Republican Oncological Dispensary"
🇷🇺Syktyvkar, Russian Federation
Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Healthcare of the Russian Federation
🇷🇺Ufa, Russian Federation
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology
🇧🇾Minsk, Belarus
State Autonomous Institution for Healthcare "Chelyabinsk Regional Clinical Hospital"
🇷🇺Chelyabinsk, Russian Federation
Kuzbass Clinical Hospital named after S.V. Belyaev
🇷🇺Kemerovo, Russian Federation
Federal State Budgetary Organization of Science "Kirov Research Institute of Hematology and Blood Transfusions of Federal Medical Biological agency"
🇷🇺Kirov, Russian Federation
Federal State Budgetary Institution "National Medical Research Centre for Hematology" of the Ministry of Health of Russian Federation (Department of Clinical Diagnostics for Hematology and Hemostasis Disorders)
🇷🇺Moscow, Russian Federation
Federal State Budgetary Institution "National Medical Research Centre for Hematology" of the Ministry of Health of Russian Federation (Department of Traumatology and Reconstructive and Restorative Orthopedics for Patients with Hemophilia)
🇷🇺Moscow, Russian Federation
State budgetary healthcare institution Leningrad Regional Clinical Hospital
🇷🇺Gatchina, Russian Federation