Phase 1/2 Dose Confirmation Study of FLT180a in Hemophilia B
Phase 1
Terminated
- Conditions
- Hemophilia B
- Interventions
- Genetic: verbrinacogene setparvovec
- Registration Number
- NCT05164471
- Lead Sponsor
- Freeline Therapeutics
- Brief Summary
Study of FLT180a gene therapy in adults with Hemophilia B. Up to 9 patients will be enrolled to receive a single dose of FLT180a and be followed for 52 weeks. Results will confirm the dose for a future Phase 3 study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Male
- Target Recruitment
- 6
Inclusion Criteria
- Diagnosis of Hemophilia B with known severe or moderately severe FIX deficiency (≤2% normal circulating FIX activity) for which the subject is on continuous, stable and adequate FIX prophylaxis
- Have acceptable laboratory values of a) Hemoglobin ≥11g/dL; b) Platelets ≥100,000 cells/µL; c) AST, ALT and alkaline phosphatase (ALP) ≤ upper limit of normal (ULN); d) Serum albumin > lower limit of normal (LLN); e) Total bilirubin ≤1.5 x ULN (except if caused by Gilbert's disease); f) Serum creatinine ≤2.0mg/dL.
- Level of neutralizing anti-AAV-S3 antibodies below the limit of the pre-established clinical cutoff using an in vitro transduction inhibition assay within the 4 weeks prior to FLT180a administration
- Has demonstrated ability to accurately, independently and in a timely manner enter bleed diary data during the lead-in study, as judged by the investigator
- At least 150 exposure days to FIX concentrates
- At least 6 months of satisfactory controlled prospective baseline data for bleeding events and FIX consumption data from the FLT-01 lead-in study (ECLIPSE)
Key
Exclusion Criteria
- Any history of alcohol or drug dependence
- Presence of neutralizing anti human FIX antibodies (inhibitor; determined by the Nijmegen modified Bethesda inhibitor assay) at the time of enrolment or a previous history of FIX inhibitor
- Subjects at high risk of thromboembolic events
- Evidence of advanced liver fibrosis
- Prior treatment with a gene transfer medicinal product
- Subjects with active hepatitis B or C
- Serological evidence of HIV-1, not controlled with anti-viral therapy and as evidenced by cluster of differentiation 4 (CD4)+ counts ≤200 μL
- Cytomegalovirus (CMV) immunoglobulin G positive subjects who are CMV polymerase chain reaction (PCR) positive at screening
- Known coagulation disorder other than hemophilia B
- High sensitivity (hs) troponin-T ≥14 pg/mL during screening
- History of uncontrolled cardiac failure, unstable angina, or myocardial infarction or other acute cardiac conditions requiring clinical management in the past 6 months
- Planned surgical procedure within the next 12 months requiring prophylactic FIX treatment
- Known active severe infection (including documented coronavirus (COVID)-19 infection), or any other significant concurrent, uncontrolled medical condition
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description FLT180a verbrinacogene setparvovec A single dose of FLT180a will be administered. Dose will be determined by enrollment cohort. The first 3 patients will receive 7.7 x 10e11 vg/kg. The dose in subsequent cohorts will be determined by the DMC based on review of data from the prior cohort(s).
- Primary Outcome Measures
Name Time Method Safety and tolerability of FLT180a as assessed by incidence and severity of AEs and SAEs Post-dose through week 52 Assessment of FIX activity levels to allow dose confirmation for future Phase 3 study Assessment at Day 182 post-dose
- Secondary Outcome Measures
Name Time Method Assessment of health-related Quality of Life Questionnaire (measuring physical health, feelings, sport and leisure, dealing with haemophilia treatment) (Haem-A-QoL questionnaire) Pre-dose and Weeks 26, 52 post-dose Spontaneous bleeding rates Pre-dose and Week 52 Assessment of Quality of Life Questionnaire (measuring mobility, self-care, usual activities, pain/discomfort & anxiety/depression)(EQ-5D-5L questionnaire). Pre-dose and Weeks 26, 52 post-dose FIX inhibitor level Pre-dose through Week 52 Measurement of Anti-AAVS3 antibodies and neutralizing antibodies Pre-dose, Week 4 and Week 26 Evaluation of AAVS3 capsid-specific T-cell reactions Pre-dose, Week 4 and Week 26 Use of immunosuppressants (dose and duration per participant) for the prevention and treatment of increased Liver Enzymes Pre-dose through Week 52 Assessment of change in annualized bleeding rate (ABR) Pre-dose and Week 52 post-dose Assessment of change in annualized FIX concentrate consumption Pre-dose and Week 52 post-dose The proportion of subjects achieving a FIX activity level between 50-150% Pre-dose and Week 52 Joint bleeding rates Pre-dose and Week 52 Number of target joints Pre-dose and Week 52 Abnormal or change from baseline findings for serum alpha-fetoprotein (AFP) levels. Pre-dose and Week 52 Assessment of Clinically significant changes in 12-lead ECG Pre-dose through Week 26 Proportion of subjects achieving FIX activity level above 40% Week 26 The proportion of subjects remaining free from continuous routine FIX prophylaxis Post dose through week 52 Abnormal or change from baseline findings for liver ultrasound Pre-dose and Week 52 Clearance of vector genomes in plasma and semen as assessed by PCR test Pre-dose through Week 52
Trial Locations
- Locations (7)
University of South Florida
🇺🇸Tampa, Florida, United States
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Glasgow Royal Infirmary
🇬🇧Glasgow, United Kingdom
Guys Hospital
🇬🇧London, United Kingdom
Royal Free London NHS Foundation Tust
🇬🇧London, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle, United Kingdom