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

Hemophilia B Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05164471
• Other study ID #: FLT180a-06
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: December 6, 2021
• Est. completion date: May 31, 2023

Study information

• Verified date: July 2023
• Source: Freeline Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: May 31, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Genetic:
• verbrinacogene setparvovec
FLT180a is a gene therapy intended to increase endogenous FIX production in adults with Hemophilia B

Locations

Country	Name	City	State
United Kingdom	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 States	University of Michigan	Ann Arbor	Michigan
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Freeline Therapeutics

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of FLT180a as assessed by incidence and severity of AEs and SAEs		Post-dose through week 52
Primary	Assessment of FIX activity levels to allow dose confirmation for future Phase 3 study		Assessment at Day 21 post-dose
Primary	Assessment of FIX activity levels to allow dose confirmation for future Phase 3 study		Assessment at Day 140 post-dose
Primary	Assessment of FIX activity levels to allow dose confirmation for future Phase 3 study		Assessment at Day 182 post-dose
Secondary	Assessment of change in annualized bleeding rate (ABR)		Pre-dose and Week 52 post-dose
Secondary	Assessment of change in annualized FIX concentrate consumption		Pre-dose and Week 52 post-dose
Secondary	Proportion of subjects achieving FIX activity level above 40%		Week 26
Secondary	The proportion of subjects remaining free from continuous routine FIX prophylaxis		Post dose through week 52
Secondary	The proportion of subjects achieving a FIX activity level between 50-150%		Pre-dose and Week 52
Secondary	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
Secondary	Joint bleeding rates		Pre-dose and Week 52
Secondary	Spontaneous bleeding rates		Pre-dose and Week 52
Secondary	Number of target joints		Pre-dose and Week 52
Secondary	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
Secondary	Measurement of Anti-AAVS3 antibodies and neutralizing antibodies		Pre-dose, Week 4 and Week 26
Secondary	Evaluation of AAVS3 capsid-specific T-cell reactions		Pre-dose, Week 4 and Week 26
Secondary	Abnormal or change from baseline findings for liver ultrasound		Pre-dose and Week 52
Secondary	Abnormal or change from baseline findings for serum alpha-fetoprotein (AFP) levels.		Pre-dose and Week 52
Secondary	FIX inhibitor level		Pre-dose through Week 52
Secondary	Use of immunosuppressants (dose and duration per participant) for the prevention and treatment of increased Liver Enzymes		Pre-dose through Week 52
Secondary	Clearance of vector genomes in plasma and semen as assessed by PCR test		Pre-dose through Week 52
Secondary	Assessment of Clinically significant changes in 12-lead ECG		Pre-dose through Week 26