A Trial of the Safety and Efficacy of Single-Dose Administration of ANB-010 in Subjects With Hemophilia A

Hemophilia A Clinical Trial

— EDELWEISS  

Official title:

An Open-Label Two-Stage Trial of the Safety, Pharmacodynamics, Biodistribution, Immunogenicity and Efficacy of Single-Dose Administration of ANB-010 in Subjects With Hemophilia A

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06185335
• Other study ID #: ANB-010-1
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 26, 2023
• Est. completion date: June 2033

Study information

• Verified date: December 2023
• Source: Biocad
• Contact: Ekaterina Fokina, MD PhD
• Phone: +7 (812) 380 49 33
• Email: fokinae[@]biocad.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 2033
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Genetic:
• ANB-010, dose 1
Adeno-associated viral vector carrying the FVIII gene single infusion at dose 1.
• ANB-010, dose 2
Adeno-associated viral vector carrying the FVIII gene single infusion at dose 2.
• ANB-010, dose 3
Adeno-associated viral vector carrying the FVIII gene single infusion at dose 3.

Locations

Country	Name	City	State
Russian Federation	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 Budgetary Institution "Moscow City Clinical Hospital named after S. P. Botkin"	Moscow
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	LLC "Medis"	Nizhny Novgorod
Russian Federation	State Novosibirsk Regional Clinical Hospital	Novosibirsk
Russian Federation	Almazov National Medical Research Centre	Saint Petersburg
Russian Federation	City Polyclinic ?37	Saint Petersburg
Russian Federation	Russian Research Institute of Hematology and Transfusiology Federal State Institution of Federal Medical and Biological Agency	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

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacodynamics of ANB-010	Evaluation of peak and steady-state FVIII concentrations	12 months
Other	Proportion of subjects with FVIII inhibitor		12 months
Other	Proportion of subjects with antibodies to capsid		12 months
Other	Proportion of subjects with anti-FVIII antibodies		12 months
Other	Proportion of subjects with T cells specific to AAV6 and FVIII transgene product		12 months
Other	ANB-010 biodistribution (in blood, saliva, urine, semen and feces)		12 months
Other	Annualized rate of spontaneous bleeding		12 months
Other	Annualized rate of intraarticular bleeding		12 months
Other	Annualized rate of trauma-related bleeding		12 months
Other	Change from baseline in the quality of life measured with Haemo-A-QoL	The assessment will be provided at scheduled assessment visits (if the scale is available in the CS).	12 months
Other	Change from baseline in the quality of life measured with EuroQol-5D-3L	The assessment will be provided at scheduled assessment visits (if the scale is available in the CS).	12 months
Other	Change from baseline in the quality of life measured with SF-36	The assessment will be provided at scheduled assessment visits (if the scale is available in the CS).	12 months
Other	Change from baseline in the assessment on the Health Needs Questionnaire for Adults with Hemophilia A at scheduled assessment visits	The assessment is be performed if the scales are available in the CS.	12 months
Other	Joint assessment based on HJHS v.2.1	The assessment is be performed if the scales are available in the CS.	12 months
Primary	Change in FVIII activity from baseline to Week 52		12 months
Primary	Assessment of ANB-010 safety	Proportion and characteristics of adverse events	12 months
Secondary	Change in FVIII activity from baseline to scheduled assessment visits	FVIII activity will be assessed at every scheduled visits and compared to baseline	12 months
Secondary	Proportion of subjects achieving clinical response	Clinical response is formulated as FVIII activity of 5-150%	12 months
Secondary	Proportion of subjects who achieved normalized response	Normalized response is formulated as FVIII activity of 50-150%	12 months
Secondary	Annualized consumption of FVIII concentrates by a subject		12 months
Secondary	Annualized bleeding rate		12 months
Secondary	Annualized rate of bleeding requiring therapy with FVIII concentrates		12 months
Secondary	Duration of response based on activity FVIII		12 months