Study of the Safety, Pharmacodynamics and Efficacy of ANB-002 in Patients With Hemophilia B (SAFRAN)

Hemophilia B Clinical Trial

Official title:

An Open-label, Non-comparative, Single Dose-Escalation Study of the Safety, Pharmacodynamics and Efficacy of ANB-002 in Patients With Hemophilia B

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06120582
• Other study ID #: ANB-002-1
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 2, 2023
• Est. completion date: November 2029

Study information

• Verified date: July 2023
• Source: Biocad
• Contact: Anna Eremeeva, MD PhD
• Phone: +7 (812) 380 49 34
• Email: eremeevaav[@]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-002 in subjects with hemophilia В. The study will have a dose-escalation design with elements of phase I/II seamless adaptive design.

Description:

The study design includes ANB-002 dose escalation in at least two cohorts. In Cohort 1, the subject treated with a single dose of ANB-002 administered as an intravenous infusion. Follow-up for the assessment of dose-limiting toxicity (DLT) will be carried out for 28 days. If no DLT events are observed in the subject of Cohort 1, the following subjects will be included in Cohort 1.

The decision to continue enrolling in Cohort 1 or dosing in Cohort 2 subjects will be made at the Independent Data Monitoring Committee (IDMC) meeting. After the IDMC makes a decision regarding the dosing in Cohort 2 subjects, further enrolment to the cohort will be carried out according to the following principles described above.

Based on the data from the follow-up period of subjects included in Сohorts 1 and 2, a potential therapeutic dose for further study will be determined. The total duration of participation of one subjects in the study will be 5 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: November 2029
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male with hemophilia B.

2. Age =18 years.

3. FIX activity at screening =2% without FIX inhibitor.

4. =150 previous exposure days of treatment with FIX concentrates.

Exclusion Criteria:

1. Previous gene therapy.

2. Other blood or hematopoietic disorders.

3. Positive Anti-AAV5 antibodies.

4. Diagnosed HIV-infection, not controlled with anti-viral therapy.

5. Hepatitis B, acute or chronic hepatitis C.

6. Any active systemic infections or recurrent infections requiring systemic therapy at screening.

7. Any other disorders associated with severe immunodeficiency.

8. Significant hepatic disorders (liver cirrhosis, liver fibrosis, etc).

9. Malignancies with remission <5 years.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Genetic:
• ANB-002, dose 1
Adeno-associated viral vector carrying the FIX gene single infusion at dose 1.
• ANB-002, dose 2
Adeno-associated viral vector carrying the FIX gene single infusion at dose 2.

Locations

Country	Name	City	State
Russian Federation	State Autonomous Institution for Healthcare "Chelyabinsk Regional Clinical Hospital"	Chelyabinsk
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	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
Primary	Change in FVIII activity from baseline		12 months; final assessment - 5 years
Primary	Proportion of subjects with adverse reactions		12 months; final assessment - 5 years
Secondary	Changes in FIX activity		5 years
Secondary	Annualized use of FIX concentrates		5 years
Secondary	Annualized bleeding rate		5 years
Secondary	Annualized rate of bleedings requiring therapy with FIX concentrates		5 years
Secondary	Changes in Haemo-A-QoL (Hemophilia-Specific Quality of Life) scores from baseline	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.	5 years
Secondary	Changes in EuroQol-5D-3L (European Quality of Life Questionnaire) scores from baseline	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.	5 years
Secondary	Changes in SF-36 (Short Form-36) scores from baseline	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.	5 years
Secondary	Response duration based on FIX activity		5 years
Secondary	Evaluation of the condition of joints based on the Hemophilia Joint Health Score (HJHS)	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.	5 years