Phase 1/2 Dose Confirmation Study of FLT180a in Hemophilia B

NCT05164471 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: FLT180a-06
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 7

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.

Conditions

Hemophilia B

Outcome Measures

Primary Outcomes (4)

• 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 21 post-dose

• Assessment of FIX activity levels to allow dose confirmation for future Phase 3 study

  Assessment at Day 140 post-dose

• Assessment of FIX activity levels to allow dose confirmation for future Phase 3 study

  Assessment at Day 182 post-dose

Secondary Outcomes (18)

• 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

• 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

• The proportion of subjects achieving a FIX activity level between 50-150%

  Pre-dose and Week 52

Study Arms (1)

FLT180a

EXPERIMENTAL

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).

Genetic: verbrinacogene setparvovec

Interventions

verbrinacogene setparvovec GENETIC

FLT180a is a gene therapy intended to increase endogenous FIX production in adults with Hemophilia B

FLT180a

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Spur Therapeutics: lead

Study Sites (7)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Glasgow Royal Infirmary

Glasgow, United Kingdom

Location

Guys Hospital

London, United Kingdom

Location

Royal Free London NHS Foundation Tust

London, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia B

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 20, 2021
• Study Start: December 6, 2021
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2023
• Last Updated: July 20, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4); US (3)