A Trial of the Safety and Efficacy of Single-Dose Administration of ANB-010 in Subjects With Hemophilia A
- Conditions
- Hemophilia A
- Interventions
- Genetic: ANB-010, dose 1Genetic: ANB-010, dose 3Genetic: ANB-010, dose 2
- Registration Number
- NCT06185335
- 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-010 in subjects with hemophilia A. The study will have a dose-escalation design with elements of phase I/II seamless adaptive design.
- Detailed Description
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.
At the second stage the main study period will include 6 subjects who will receive ANB-010 at the optimal dose selected based on the results of stage 1 data analysis.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 50
-
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 ANB-010, dose 1 Subjects in Cohort 1 will receive ANB-010 at a dose 1. ANB-010 will be administered to the first subject in group 1. Not earlier than in 28 days, the investigational product will be administered to the next two subjects in Cohort 1 (with an interval of at least 24 hours). Cohort 3 ANB-010, dose 3 Subjects in Cohort 1 will receive ANB-010 at a dose 1. Not earlier than 28 days after the ANB-010 administration to the third subject in Cohort 2, the investigational product will be administered to the first subject in Cohort 3. Not earlier than 28 days after the ANB-010 administration to the first subject in Cohort 3, the investigational product will be administered to the next two subjects in Cohort 3 (with an interval of at least 24 hours). Cohort 2 ANB-010, dose 2 Subjects in Cohort 1 will receive ANB-010 at a dose 1. Not earlier than 28 days after the ANB-010 administration to the third subject in Cohort 1, the investigational product will be administered to the first subject in Cohort 2. Not earlier than 28 days after the ANB-010 administration to the first subject in Cohort 2, the investigational product will be administered to the next two subjects in Cohort 2 (with an interval of at least 24 hours).
- Primary Outcome Measures
Name Time Method Change in FVIII activity from baseline to Week 52 12 months Assessment of ANB-010 safety 12 months Proportion and characteristics of adverse events
- Secondary Outcome Measures
Name Time Method Change in FVIII activity from baseline to scheduled assessment visits 12 months FVIII activity will be assessed at every scheduled visits and compared to baseline
Proportion of subjects achieving clinical response 12 months Clinical response is formulated as FVIII activity of 5-150%
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 Normalized response is formulated as FVIII activity of 50-150%
Trial Locations
- Locations (17)
State Autonomous Institution for Healthcare "Chelyabinsk Regional Clinical Hospital"
🇷🇺Chelyabinsk, Russian Federation
State Autonomous Institution for Healthcare of Sverdlovsk region "Sverdlovsk Regional Clinical Hospital №1"
🇷🇺Ekaterinburg, Russian Federation
State budgetary healthcare institution Leningrad Regional Clinical Hospital
🇷🇺Gatchina, 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
Research Center for Hematology MHSD RF
🇷🇺Moscow, Russian Federation
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