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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Adeno-associated viral vector carrying the FIX gene single infusion at dose 1.
Adeno-associated viral vector carrying the FIX gene single infusion at dose 2.
Adeno-associated viral vector carrying the FIX gene single infusion at dose 3.
Change in FIX activity from baseline
Time frame: 12 months; final assessment - 5 years
Proportion of subjects with adverse reactions
Time frame: 12 months; final assessment - 5 years
Changes in FIX activity
Time frame: 5 years
Annualized use of FIX concentrates
Time frame: 5 years
Annualized bleeding rate
Time frame: 5 years
Annualized rate of bleedings requiring therapy with FIX concentrates
Time frame: 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.
Time frame: 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.
Time frame: 5 years
Changes in SF-36 (Short Form-36) scores from baseline
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Republican Scientific and Practical Center for Radiation Medicine and Human Ecology
Homyel, Belarus
RECRUITINGMinsk Scientific and Practical Center for Surgery, Transplantology and Hematology
Minsk, Belarus
RECRUITINGState Autonomous Institution for Healthcare "Chelyabinsk Regional Clinical Hospital"
Chelyabinsk, Russia
RECRUITINGState budgetary healthcare institution Leningrad Regional Clinical Hospital
Gatchina, Russia
RECRUITINGKuzbass Clinical Hospital named after S.V. Belyaev
Kemerovo, Russia
RECRUITINGFederal State Budgetary Organization of Science "Kirov Research Institute of Hematology and Blood Transfusions of Federal Medical Biological agency"
Kirov, Russia
RECRUITINGFederal 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, Russia
RECRUITINGFederal 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, Russia
RECRUITINGFederal Budgetary Institution "Moscow City Clinical Hospital named after S. P. Botkin"
Moscow, Russia
RECRUITINGLLC "Medis"
Nizhny Novgorod, Russia
RECRUITING...and 7 more locations
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.
Time frame: 5 years
Response duration based on FIX activity
Time frame: 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.
Time frame: 5 years