Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Subjects in Cohort 1 will receive ANB-002 (arvenacogene sanparvovec) 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 | Experimental | Subjects in Cohort 2 will receive ANB-002 (arvenacogene sanparvovec) at a dose 2. The decision to continue enrolling in Cohort 1 or dosing in Cohort 2 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. |
|
| Cohort 3 | Experimental | Subjects in Cohort 3 will receive ANB-002 (arvenacogene sanparvovec) at a dose 3. The decision to continue enrolling in Cohort 2 or dosing in Cohort 3 will be made at the IDMC meeting. |
|
| Cohort 4 | Experimental | Exploratory cohort. Subjects in Cohort 4 (with anti-AAV5 antibodies and/or hepatitis B in anamnesis) will receive ANB-002 (arvenacogene sanparvovec) at the dose 3. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ANB-002, dose 1 | Genetic | Adeno-associated viral vector carrying the FIX gene single infusion at dose 1. |
|
| Measure | Description | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in FIX activity | 5 years | |
| Annualized use of FIX concentrates | 5 years | |
| Annualized bleeding rate |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anna Eremeeva, MD PhD | Contact | +7 (812) 380 49 34 | ext. 6963 | eremeevaav@biocad.ru |
| Name | Affiliation | Role |
|---|---|---|
| Arina V Zinkina-Orikhan, MD | Director of Clinical Development Department, BIOCAD | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Republican Scientific and Practical Center for Radiation Medicine and Human Ecology | Recruiting | Homyel | 246040 | Belarus |
Not provided
| Label | URL |
|---|---|
| Related Info | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ANB-002, dose 2 | Genetic | Adeno-associated viral vector carrying the FIX gene single infusion at dose 2. |
|
|
| ANB-002, dose 3 | Genetic | Adeno-associated viral vector carrying the FIX gene single infusion at dose 3. |
|
|
| 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 | 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. | 5 years |
| Changes in EuroQol-5D-3L (European Quality of Life Questionnaire) scores from baseline | 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. | 5 years |
| Changes in SF-36 (Short Form-36) scores from baseline | 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. | 5 years |
| Response duration based on FIX activity | 5 years |
| Evaluation of the condition of joints based on the Hemophilia Joint Health Score (HJHS) | 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. | 5 years |
| Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology | Recruiting | Minsk | 220089 | Belarus |
|
| State Autonomous Institution for Healthcare "Chelyabinsk Regional Clinical Hospital" | Recruiting | Chelyabinsk | 454048 | Russia |
|
| State budgetary healthcare institution Leningrad Regional Clinical Hospital | Recruiting | Gatchina | 188300 | Russia |
|
| Kuzbass Clinical Hospital named after S.V. Belyaev | Recruiting | Kemerovo | 650066 | Russia |
|
| Federal State Budgetary Organization of Science "Kirov Research Institute of Hematology and Blood Transfusions of Federal Medical Biological agency" | Recruiting | Kirov | 610027 | Russia |
|
| 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) | Recruiting | Moscow | 125167 | Russia |
|
| 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) | Recruiting | Moscow | 125167 | Russia |
|
| Federal Budgetary Institution "Moscow City Clinical Hospital named after S. P. Botkin" | Recruiting | Moscow | 125284 | Russia |
|
| LLC "Medis" | Recruiting | Nizhny Novgorod | 603137 | Russia |
|
| State Novosibirsk Regional Clinical Hospital | Recruiting | Novosibirsk | 630087 | Russia |
|
| Russian Research Institute of Hematology and Transfusiology Federal State Institution of Federal Medical and Biological Agency | Recruiting | Saint Petersburg | 191024 | Russia |
|
| City Polyclinic №37 | Recruiting | Saint Petersburg | 191186 | Russia |
|
| Almazov National Medical Research Centre | Recruiting | Saint Petersburg | 197341 | Russia |
|
| Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Healthcare of the Russian Federation | Recruiting | Samara | 443099 | Russia |
|
| State Institution "Komi Republican Oncological Dispensary" | Recruiting | Syktyvkar | 167904 | Russia |
|
| Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Healthcare of the Russian Federation | Recruiting | Ufa | 450008 | Russia |
|
| ID | Term |
|---|---|
| D002836 | Hemophilia B |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
Not provided
Not provided