Clinical trial NCT06120582: Study of the Safety, Pharmacodynamics and Efficacy of ANB-002 in Patients With Hemophilia B (SAFRAN)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hemophilia B
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2023-11-07
Enrollment: 28
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-002 in subjects with hemophilia В. The study will have a dose-escalation design with elements of phase I/II seamless adaptive design.

Detailed description: The study design includes ANB-002 dose escalation in at three cohorts. In Cohort 1, the subject is treated with a single dose of ANB-002 (dose 1) 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.

In Cohort 2, the subjects are treated with a single dose of ANB-002 (dose 2). In Cohort 3, the subject are treated with a single dose of ANB-002 (dose 3).

The decision to continue enrolling in cohorts will be made at the Independent Data Monitoring Committee (IDMC) meeting. After the IDMC makes a decision regarding the dosing subjects, further enrolment to the cohort will be carried out.

Based on the data from the follow-up period of subjects included in Сohorts 1-3, a potential therapeutic dose for further study will be determined and additional patients will be included to recieve this dose.

In exploratory Cohort 4 patients with anti-AAV5 antibodies and/or hepatitis B in anamnesis will be included. These subjects will recieve the dose 3 of ANB-002.

The total duration of participation of one subjects in the study will be 5 years.

Eligibility criteria: 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 (for Cohorts 1-3).
4. Diagnosed HIV-infection, not controlled with anti-viral therapy.
5. Hepatitis B (for Cohorts 1-3), 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.

Primary outcomes:
measure: Change in FIX activity from baseline
timeFrame: 12 months; final assessment - 5 years
measure: Proportion of subjects with adverse reactions
timeFrame: 12 months; final assessment - 5 years
Secondary outcomes:
measure: Changes in FIX activity
timeFrame: 5 years
measure: Annualized use of FIX concentrates
timeFrame: 5 years
measure: Annualized bleeding rate
timeFrame: 5 years
measure: Annualized rate of bleedings requiring therapy with FIX concentrates
timeFrame: 5 years
measure: Changes in Haemo-A-QoL (Hemophilia-Specific Quality of Life) scores from baseline
timeFrame: 5 years
measure: Changes in EuroQol-5D-3L (European Quality of Life Questionnaire) scores from baseline
timeFrame: 5 years
measure: Changes in SF-36 (Short Form-36) scores from baseline
timeFrame: 5 years
measure: Response duration based on FIX activity
timeFrame: 5 years
measure: Evaluation of the condition of joints based on the Hemophilia Joint Health Score (HJHS)
timeFrame: 5 years
Other outcomes:
Locations:
city: Gomel
country: Belarus
facility: Republican Scientific and Practical Center for Radiation Medicine and Human Ecology
city: Minsk
country: Belarus
facility: Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology
city: Chelyabinsk
country: Russian Federation
facility: State Autonomous Institution for Healthcare "Chelyabinsk Regional Clinical Hospital"
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: 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, MD
role: STUDY_DIRECTOR
References: