Hemophilia A
Conditions
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.
Interventions
GENETICANB-010, dose 1
Adeno-associated viral vector carrying the FVIII gene single infusion at dose 1.
GENETICANB-010, dose 2
Adeno-associated viral vector carrying the FVIII gene single infusion at dose 2.
GENETICANB-010, dose 3
Adeno-associated viral vector carrying the FVIII gene single infusion at dose 3.
Sponsors
Biocad
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. Male subjects aged ≥18 years at the time of signing the informed consent form. 3\. Established diagnosis of hemophilia A with a documented history of endogenous FVIII activity ≤1% AND ≤2% at screening. 4\. Therapy with FVIII concentrates for at least 150 exposure days.
Exclusion criteria
1. History of use of any gene therapy product. 2. Use of emicizumab within less than 6 months before the date of signing the ICF. 3. The presence of other blood or hematopoietic disorders other than hemophilia A. 4. Presence of AAV6 antibodies detected by ELISA. 5. BMI \<16 kg/m² or ≥35 kg/m². 6. Diagnosis of HIV infection. 7. HBV infection. 8. HCV infection. 9. Any active systemic infections or recurrent infections requiring systemic therapy at screening. 10. Any other disorders associated with severe immunodeficiency. 11. Relevant hepatic disorders or conditions that can be a symptom of existing liver disorder. 12. Malignancies with remission duration of less than 5 years at the time of signing the ICF, except for cured basal cell carcinoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects who achieved normalized response | 12 months | Normalized response is formulated as FVIII activity of 50-150% |
| Annualized consumption of FVIII concentrates by a subject | 12 months | — |
| 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 |
| Annualized rate of bleeding requiring therapy with FVIII concentrates | 12 months | — |
| Duration of response based on activity FVIII | 12 months | — |
| Annualized bleeding rate | 12 months | — |
| Proportion of subjects achieving clinical response | 12 months | Clinical response is formulated as FVIII activity of 5-150% |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the quality of life measured with Haemo-A-QoL | 12 months | The assessment will be provided at scheduled assessment visits (if the scale is available in the CS). |
| Change from baseline in the quality of life measured with EuroQol-5D-3L | 12 months | The assessment will be provided at scheduled assessment visits (if the scale is available in the CS). |
| Pharmacodynamics of ANB-010 | 12 months | Evaluation of peak and steady-state FVIII concentrations |
| Change from baseline in the assessment on the Health Needs Questionnaire for Adults with Hemophilia A at scheduled assessment visits | 12 months | The assessment is be performed if the scales are available in the CS. |
| Joint assessment based on HJHS v.2.1 | 12 months | The assessment is be performed if the scales are available in the CS. |
| Change from baseline in the quality of life measured with SF-36 | 12 months | The assessment will be provided at scheduled assessment visits (if the scale is available in the CS). |
| Proportion of subjects with FVIII inhibitor | 12 months | — |
| Proportion of subjects with antibodies to capsid | 12 months | — |
| Proportion of subjects with anti-FVIII antibodies | 12 months | — |
| Proportion of subjects with T cells specific to AAV6 and FVIII transgene product | 12 months | — |
| ANB-010 biodistribution (in blood, saliva, urine, semen and feces) | 12 months | — |
| Annualized rate of spontaneous bleeding | 12 months | — |
| Annualized rate of intraarticular bleeding | 12 months | — |
| Annualized rate of trauma-related bleeding | 12 months | — |
Countries
Russia
Outcome results
None listed