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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT05164471
Recruitment Status : Active, not recruiting
First Posted : December 20, 2021
Last Update Posted : October 4, 2022
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Hemophilia B Genetic: verbrinacogene setparvovec Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : December 6, 2021
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: FLT180a
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
FLT180a is a gene therapy intended to increase endogenous FIX production in adults with Hemophilia B

Primary Outcome Measures :
  1. Safety and tolerability of FLT180a as assessed by incidence and severity of AEs and SAEs [ Time Frame: Post-dose through week 52 ]
  2. Assessment of FIX activity levels to allow dose confirmation for future Phase 3 study [ Time Frame: Assessment at Day 21 post-dose ]
  3. Assessment of FIX activity levels to allow dose confirmation for future Phase 3 study [ Time Frame: Assessment at Day 140 post-dose ]
  4. Assessment of FIX activity levels to allow dose confirmation for future Phase 3 study [ Time Frame: Assessment at Day 182 post-dose ]

Secondary Outcome Measures :
  1. Assessment of change in annualized bleeding rate (ABR) [ Time Frame: Pre-dose and Week 52 post-dose ]
  2. Assessment of change in annualized FIX concentrate consumption [ Time Frame: Pre-dose and Week 52 post-dose ]
  3. Proportion of subjects achieving FIX activity level above 40% [ Time Frame: Week 26 ]
  4. The proportion of subjects remaining free from continuous routine FIX prophylaxis [ Time Frame: Post dose through week 52 ]
  5. The proportion of subjects achieving a FIX activity level between 50-150% [ Time Frame: Pre-dose and Week 52 ]
  6. Assessment of health-related Quality of Life Questionnaire (measuring physical health, feelings, sport and leisure, dealing with haemophilia treatment) (Haem-A-QoL questionnaire) [ Time Frame: Pre-dose and Weeks 26, 52 post-dose ]
  7. Joint bleeding rates [ Time Frame: Pre-dose and Week 52 ]
  8. Spontaneous bleeding rates [ Time Frame: Pre-dose and Week 52 ]
  9. Number of target joints [ Time Frame: Pre-dose and Week 52 ]
  10. Assessment of Quality of Life Questionnaire (measuring mobility, self-care, usual activities, pain/discomfort & anxiety/depression)(EQ-5D-5L questionnaire). [ Time Frame: Pre-dose and Weeks 26, 52 post-dose ]
  11. Measurement of Anti-AAVS3 antibodies and neutralizing antibodies [ Time Frame: Pre-dose, Week 4 and Week 26 ]
  12. Evaluation of AAVS3 capsid-specific T-cell reactions [ Time Frame: Pre-dose, Week 4 and Week 26 ]
  13. Abnormal or change from baseline findings for liver ultrasound [ Time Frame: Pre-dose and Week 52 ]
  14. Abnormal or change from baseline findings for serum alpha-fetoprotein (AFP) levels. [ Time Frame: Pre-dose and Week 52 ]
  15. FIX inhibitor level [ Time Frame: Pre-dose through Week 52 ]
  16. Use of immunosuppressants (dose and duration per participant) for the prevention and treatment of increased Liver Enzymes [ Time Frame: Pre-dose through Week 52 ]
  17. Clearance of vector genomes in plasma and semen as assessed by PCR test [ Time Frame: Pre-dose through Week 52 ]
  18. Assessment of Clinically significant changes in 12-lead ECG [ Time Frame: Pre-dose through Week 26 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05164471

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United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
United States, Florida
University of South Florida
Tampa, Florida, United States, 33612
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
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 Kingdom
Sponsors and Collaborators
Freeline Therapeutics
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Responsible Party: Freeline Therapeutics Identifier: NCT05164471    
Other Study ID Numbers: FLT180a-06
First Posted: December 20, 2021    Key Record Dates
Last Update Posted: October 4, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked