Brief Title
Phase 1/2 Dose Confirmation Study of FLT180a in Hemophilia B
Official Title
A Dose Confirmation Study of FLT180a (Adeno-associated Viral Vector Containing the Padua Variant of a Codon-optimized Human Factor IX Gene) in Adult Subjects With Hemophilia B
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Safety and tolerability of FLT180a as assessed by incidence and severity of AEs and SAEs
Secondary Outcome
Assessment of change in annualized bleeding rate (ABR)
Condition
Hemophilia B
Intervention
verbrinacogene setparvovec
Study Arms / Comparison Groups
FLT180a
Description: 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).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Genetic
Estimated Enrollment
9
Start Date
December 6, 2021
Completion Date
November 2023
Primary Completion Date
November 2023
Eligibility Criteria
Key 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
Gender
Male
Ages
18 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
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Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT05164471
Organization ID
FLT180a-06
Responsible Party
Sponsor
Study Sponsor
Freeline Therapeutics
Study Sponsor
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Verification Date
October 2022