Clinical trial NCT06185335: A Trial of the Safety and Efficacy of Single-Dose Administration of ANB-010 in Subjects With Hemophilia A
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hemophilia A
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2023-12-29
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in FVIII activity from baseline to Week 52
timeFrame: 12 months
measure: Assessment of ANB-010 safety
timeFrame: 12 months
Secondary outcomes:
measure: Change in FVIII activity from baseline to scheduled assessment visits
timeFrame: 12 months
measure: Proportion of subjects achieving clinical response
timeFrame: 12 months
measure: Proportion of subjects who achieved normalized response
timeFrame: 12 months
measure: Annualized consumption of FVIII concentrates by a subject
timeFrame: 12 months
measure: Annualized bleeding rate
timeFrame: 12 months
measure: Annualized rate of bleeding requiring therapy with FVIII concentrates
timeFrame: 12 months
measure: Duration of response based on activity FVIII
timeFrame: 12 months
Other outcomes:
measure: Pharmacodynamics of ANB-010
timeFrame: 12 months
measure: Proportion of subjects with FVIII inhibitor
timeFrame: 12 months
measure: Proportion of subjects with antibodies to capsid
timeFrame: 12 months
measure: Proportion of subjects with anti-FVIII antibodies
timeFrame: 12 months
measure: Proportion of subjects with T cells specific to AAV6 and FVIII transgene product
timeFrame: 12 months
measure: ANB-010 biodistribution (in blood, saliva, urine, semen and feces)
timeFrame: 12 months
measure: Annualized rate of spontaneous bleeding
timeFrame: 12 months
measure: Annualized rate of intraarticular bleeding
timeFrame: 12 months
measure: Annualized rate of trauma-related bleeding
timeFrame: 12 months
measure: Change from baseline in the quality of life measured with Haemo-A-QoL
timeFrame: 12 months
measure: Change from baseline in the quality of life measured with EuroQol-5D-3L
timeFrame: 12 months
measure: Change from baseline in the quality of life measured with SF-36
timeFrame: 12 months
measure: Change from baseline in the assessment on the Health Needs Questionnaire for Adults with Hemophilia A at scheduled assessment visits
timeFrame: 12 months
measure: Joint assessment based on HJHS v.2.1
timeFrame: 12 months
Locations:
city: Chelyabinsk
country: Russian Federation
facility: State Autonomous Institution for Healthcare "Chelyabinsk Regional Clinical Hospital"
city: Ekaterinburg
country: Russian Federation
facility: State Autonomous Institution for Healthcare of Sverdlovsk region "Sverdlovsk Regional Clinical Hospital №1"
city: Gatchina
country: Russian Federation
facility: State budgetary healthcare institution Leningrad Regional Clinical Hospital
city: Kemerovo
country: Russian Federation
facility: Kuzbass Clinical Hospital named after S.V. Belyaev
city: Kirov
country: Russian Federation
facility: Federal State Budgetary Organization of Science "Kirov Research Institute of Hematology and Blood Transfusions of Federal Medical Biological agency"
city: Moscow
country: Russian Federation
facility: 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)
city: Moscow
country: Russian Federation
facility: 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)
city: Moscow
country: Russian Federation
facility: Research Center for Hematology MHSD RF
city: Moscow
country: Russian Federation
facility: Federal Budgetary Institution "Moscow City Clinical Hospital named after S. P. Botkin"
city: Nizhny Novgorod
country: Russian Federation
facility: LLC "Medis"
city: Novosibirsk
country: Russian Federation
facility: State Novosibirsk Regional Clinical Hospital
city: Saint Petersburg
country: Russian Federation
facility: Russian Research Institute of Hematology and Transfusiology Federal State Institution of Federal Medical and Biological Agency
city: Saint Petersburg
country: Russian Federation
facility: City Polyclinic №37
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre
city: Samara
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Healthcare of the Russian Federation
city: Syktyvkar
country: Russian Federation
facility: State Institution "Komi Republican Oncological Dispensary"
city: Ufa
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Healthcare of the Russian Federation
Study officials:
affiliation: Director of Clinical Development Department, BIOCAD
name: Arina V Zinkina-Orikhan, PhD
role: STUDY_DIRECTOR
References: