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

December 14, 2023 updated by: Biocad

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Ekaterina Fokina, MD PhD
  • Phone Number: 6768 +7 (812) 380 49 33
  • Email: fokinae@biocad.ru

Study Locations

  • Russian Federation
      • Chelyabinsk, Russian Federation, 454048
        • Recruiting
        • State Autonomous Institution for Healthcare "Chelyabinsk Regional Clinical Hospital"
        • Contact:
          • Aleksandr Korobkin
        • Contact:
      • Ekaterinburg, Russian Federation, 620102
        • Recruiting
        • State Autonomous Institution for Healthcare of Sverdlovsk region "Sverdlovsk Regional Clinical Hospital №1"
        • Contact:
          • Tatyana Konstantinova
        • Contact:
      • Gatchina, Russian Federation, 188300
        • Recruiting
        • State Budgetary Healthcare Institution Leningrad Regional Clinical Hospital
        • Contact:
          • Vladimir V Vorobyev
          • Phone Number: +7 (812) 670 18 88
          • Email: lokb@47lokb.ru
      • Kemerovo, Russian Federation, 650066
        • Recruiting
        • Kuzbass Clinical Hospital named after S.V. Belyaev
        • Contact:
      • Kirov, Russian Federation, 610027
        • Recruiting
        • Federal State Budgetary Organization of Science "Kirov Research Institute of Hematology and Blood Transfusions of Federal Medical Biological agency"
        • Contact:
          • Margarita Timofeeva
        • Contact:
      • Moscow, Russian Federation, 125167
        • Recruiting
        • 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)
        • Contact:
          • Nadezhda Zozulya
        • Contact:
      • Moscow, Russian Federation, 125167
        • Recruiting
        • 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)
        • Contact:
        • Contact:
          • Vladimir Zorenko
      • Moscow, Russian Federation, 125284
        • Recruiting
        • Federal Budgetary Institution "Moscow City Clinical Hospital named after S. P. Botkin"
        • Contact:
          • Vadim Ptushkin
        • Contact:
      • Moscow, Russian Federation, 125167
        • Recruiting
        • Research Center for Hematology MHSD RF
      • Nizhny Novgorod, Russian Federation, 603137
        • Recruiting
        • Llc "Medis"
        • Contact:
          • Svetlana A Volkova
          • Phone Number: +7 (831) 215 20 00
          • Email: info@medisnn.ru
      • Novosibirsk, Russian Federation, 630087
        • Recruiting
        • State Novosibirsk Regional Clinical Hospital
        • Contact:
      • Saint Petersburg, Russian Federation, 197341
        • Recruiting
        • Almazov National Medical Research Centre
        • Contact:
          • Vladimir Ivanov
        • Contact:
      • Saint Petersburg, Russian Federation, 191024
        • Recruiting
        • Russian Research Institute of Hematology and Transfusiology Federal State Institution of Federal Medical and Biological Agency
        • Contact:
          • Sergey Voloshin
        • Contact:
          • Phone Number: +7 (812) 309 79 81
      • Saint Petersburg, Russian Federation, 191186
        • Recruiting
        • City Polyclinic №37
        • Contact:
          • Tatyana Andreeva
      • Samara, Russian Federation, 443099
        • Recruiting
        • Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Healthcare of the Russian Federation
        • Contact:
          • Igor Davydkin
        • Contact:
      • Syktyvkar, Russian Federation, 167904
        • Recruiting
        • State Institution "Komi Republican Oncological Dispensary"
        • Contact:
          • Andrey Proydakov
        • Contact:
      • Ufa, Russian Federation, 450008
        • Recruiting
        • Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Healthcare of the Russian Federation
        • Contact:
          • Bulat Bakhirov

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
Subjects in Cohort 1 will receive ANB-010 at a dose 1. ANB-010 will be administered to the first subject in group 1. Not earlier than in 28 days, the investigational product will be administered to the next two subjects in Cohort 1 (with an interval of at least 24 hours).
Genetic: ANB-010, dose 1
Adeno-associated viral vector carrying the FVIII gene single infusion at dose 1.
Experimental: Cohort 2
Subjects in Cohort 1 will receive ANB-010 at a dose 1. Not earlier than 28 days after the ANB-010 administration to the third subject in Cohort 1, the investigational product will be administered to the first subject in Cohort 2. Not earlier than 28 days after the ANB-010 administration to the first subject in Cohort 2, the investigational product will be administered to the next two subjects in Cohort 2 (with an interval of at least 24 hours).
Genetic: ANB-010, dose 2
Adeno-associated viral vector carrying the FVIII gene single infusion at dose 2.
Experimental: Cohort 3
Subjects in Cohort 1 will receive ANB-010 at a dose 1. Not earlier than 28 days after the ANB-010 administration to the third subject in Cohort 2, the investigational product will be administered to the first subject in Cohort 3. Not earlier than 28 days after the ANB-010 administration to the first subject in Cohort 3, the investigational product will be administered to the next two subjects in Cohort 3 (with an interval of at least 24 hours).
Genetic: ANB-010, dose 3
Adeno-associated viral vector carrying the FVIII gene single infusion at dose 3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in FVIII activity from baseline to Week 52
Time Frame: 12 months
12 months
Assessment of ANB-010 safety
Time Frame: 12 months
Proportion and characteristics of adverse events
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in FVIII activity from baseline to scheduled assessment visits
Time Frame: 12 months
FVIII activity will be assessed at every scheduled visits and compared to baseline
12 months
Proportion of subjects achieving clinical response
Time Frame: 12 months
Clinical response is formulated as FVIII activity of 5-150%
12 months
Proportion of subjects who achieved normalized response
Time Frame: 12 months
Normalized response is formulated as FVIII activity of 50-150%
12 months
Annualized consumption of FVIII concentrates by a subject
Time Frame: 12 months
12 months
Annualized bleeding rate
Time Frame: 12 months
12 months
Annualized rate of bleeding requiring therapy with FVIII concentrates
Time Frame: 12 months
12 months
Duration of response based on activity FVIII
Time Frame: 12 months
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacodynamics of ANB-010
Time Frame: 12 months
Evaluation of peak and steady-state FVIII concentrations
12 months
Proportion of subjects with FVIII inhibitor
Time Frame: 12 months
12 months
Proportion of subjects with antibodies to capsid
Time Frame: 12 months
12 months
Proportion of subjects with anti-FVIII antibodies
Time Frame: 12 months
12 months
Proportion of subjects with T cells specific to AAV6 and FVIII transgene product
Time Frame: 12 months
12 months
ANB-010 biodistribution (in blood, saliva, urine, semen and feces)
Time Frame: 12 months
12 months
Annualized rate of spontaneous bleeding
Time Frame: 12 months
12 months
Annualized rate of intraarticular bleeding
Time Frame: 12 months
12 months
Annualized rate of trauma-related bleeding
Time Frame: 12 months
12 months
Change from baseline in the quality of life measured with Haemo-A-QoL
Time Frame: 12 months
The assessment will be provided at scheduled assessment visits (if the scale is available in the CS).
12 months
Change from baseline in the quality of life measured with EuroQol-5D-3L
Time Frame: 12 months
The assessment will be provided at scheduled assessment visits (if the scale is available in the CS).
12 months
Change from baseline in the quality of life measured with SF-36
Time Frame: 12 months
The assessment will be provided at scheduled assessment visits (if the scale is available in the CS).
12 months
Change from baseline in the assessment on the Health Needs Questionnaire for Adults with Hemophilia A at scheduled assessment visits
Time Frame: 12 months
The assessment is be performed if the scales are available in the CS.
12 months
Joint assessment based on HJHS v.2.1
Time Frame: 12 months
The assessment is be performed if the scales are available in the CS.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biocad

Investigators

  • Study Director: Arina V Zinkina-Orikhan, PhD, Director of Clinical Development Department, BIOCAD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 26, 2023

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

June 1, 2033

Study Registration Dates

First Submitted

December 1, 2023

First Submitted That Met QC Criteria

December 14, 2023

First Posted (Actual)

December 29, 2023

Study Record Updates

Last Update Posted (Actual)

December 29, 2023

Last Update Submitted That Met QC Criteria

December 14, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANB-010-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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