Hemophilia B
Conditions
Brief summary
The aim of the study is to demonstrate non-inferiority of ANB-002 compared with preventive use of coagulation factor IX (FIX) in adult subjects with hemophilia B with FIX activity ≤2% and without FIX inhibitor. The study will have an open-label single-arm design.
Detailed description
After signing the ICF and screening examination the subjects are to be included in the Non-interventional lead-in period in which the subject will receive standard FIX prevention. The lead-in period will last for at least 6 month for every subject. After completiong the lead-in period subjects will enter the main (interventional) period. At the first visit of the main period subjects will recieve investigational product ANB-002. The main period ends 18 months after the administration of ANB-002, after which subjects will switch to the follow-up period and will be evaluated up to 5 years after the ANB-002 infusion.
Interventions
GENETICANB-002
Adeno-associated viral vector carrying the FIX gene single infusion
Sponsors
Biocad
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men diagnosed with hemophilia B aged 18 or older * FIX activity ≤2% * Absense of FIX inhibitor * ≥150 previous exposure days of treatment with FIX concentrates
Exclusion criteria
* Any diseases of blood and hematopoietic organs other than hemophilia B * A history of any gene therapy, including ANB-002 * Diagnosed HIV-infection, not controlled with anti-viral therapy * Active HBV or HCV infection * Anti-AAV5 antibodies * Any active systemic infections or recurrent infections requiring systemic therapy * Any other disorders associated with severe immunodeficiency * Relevant hepatic disorders or conditions that can be a symptom of existing liver disorder * Malignancies with less than 5 years of remission
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized bleeding rate (ABR) before and after a single dose of ANB-002 | Lead-in period: at least 6 months prior to ANB-002 infusion (Lead-in arm); Month 12 to Month 18 post infusion (ANB-002 arm) | A comparison will be made between the mean ABR values in the lead-in period and within 12 months after stabilization of endogenous FIX activity, but not later than 18 months after the ANB-002 dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with spontaneous bleedings | 18 months after drug administration; final assessment - 5 years | — |
| Proportion of subjects with bleedings requiring FIX concentrate therapy | 18 months after drug administration; final assessment - 5 years | — |
| Annualized rate of bleedings requiring therapy with FIX concentrates | 18 months after drug administration; final assessment - 5 years | — |
| Proportion of subjects without bleeding within 12 months after stabilization of endogenous FIX activity | 12 months after stabilization of endogenous FIX activity | — |
| Proportion of subjects achieving clinical response | 18 months after drug administration | Clinical Response is defined as FIX activity 5-150% |
| Proportion of subjects achieving a normalized response | 18 months after drug administration | Normalized response is defined as FIX activity 50-150% |
| FIX activity | 18 months after drug administration; final assessment - 5 years | — |
| Annualized FIX consumption | 18 months after drug administration; final assessment - 5 years | — |
| Proportion of subjects not receiving FIX prevention | 18 months after drug administration | — |
| Annualized bleeding rate (ABR) | 18 months after drug administration; final assessment - 5 years | — |
| Annualized rate of spontaneous bleedings | 18 months after drug administration; final assessment - 5 years | — |
| Proportion of subjects with hemarthrosis | 18 months after drug administration; final assessment - 5 years | — |
| Annualized hemarthrosis rate | 18 months after drug administration; final assessment - 5 years | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| EuroQol-5D-3L (European Quality of Life Questionnaire) score | 18 months after drug administration; final assessment - 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. |
| SF-36 (Short Form-36) score | 18 months after drug administration; final assessment - 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 |
| Evaluation of the condition of joints based on the Hemophilia Joint Health Score (HJHS) | 18 months after drug administration; final assessment - 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. |
| Proportion of subjects with adverse reactions | 18 months after drug administration; final assessment - 5 years | — |
| Haemo-A-QoL (Hemophilia-Specific Quality of Life) score | 18 months after drug administration; final assessment - 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. |
Countries
Russia, Thailand
Contacts
Primary ContactAnna Eremeeva, MD PhD
Outcome results
None listed