Phase 1 Gene Therapy study of SB-FIX in Severe Haemophilia B
Research type
Research Study
Full title
A Phase I, Open-Label, Ascending Dose Study to Assess the Safety and Tolerability of AAV2/6 Factor IX Gene Therapy via Zinc Finger Nuclease (ZFN) mediated targeted integration of SB-FIX in Subjects with Severe Haemophilia B
IRAS ID
240955
Contact name
Michael Laffan
Contact email
Sponsor organisation
Sangamo Therapeutics, Inc.
Eudract number
2017-004805-42
Clinicaltrials.gov Identifier
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Summary of Research
This is an open label ascending dose study for people with severe haemophilia B using SB-FIX, a genome editing investigational product using zinc finger nucleases. SB-FIX is an intravenously delivered and inserts a correct copy of the Factor 9 gene into the liver cells with the goal of lifelong therapeutic production of the Factor IX clotting factor.The purpose of this study is to see if receiving SB-FIX is safe and tolerable. This study will also look at what doses of SB-FIX are safe for people to receive and to evaluate the potential effect of SB-FIX for improving blood clotting.
This research study will test three doses (low, mid, and high level doses) and will determine the highest dose that can be given that is safe and tolerable.
Summary of Results
The FIXtendz study was designed to assess the safety, tolerability, and effectiveness of SB-FIX, an investigational genome editing therapy for participants with haemophilia B (a genetic bleeding disorder in which affected individuals have insufficient level of blood protein called factor IX). The aim of treatment with SB-FIX was to make a permanent change to the DNA of the participant by inserting a healthy copy of the factor IX gene into the DNA of the participant’s liver cells. This summary explains what SB-FIX is made of, how it was expected to work, and the outcome of the study.SB-FIX includes 3 components:
• Two zinc finger nucleases, which are small proteins that work together and act like genetic scissors to cut at specific locations in DNA
• A healthy factor IX gene surrounded by regulatory elements
Each component was packaged into individual delivery vectors, specifically, recombinant adeno-associated viruses 2/6 (rAAV2/6). Prior to use in SB-FIX, the adeno-associated viruses were modified in the laboratory so they could no longer grow or reproduce in the body.SB-FIX delivery to liver - Following infusion of SB-FIX, the delivery vectors containing the 3 components are intended to target the liver, where the zinc finger nucleases in SB-FIX were designed to recognize specific regions of DNA in the albumin gene in the participant’s liver cells.
SB-FIX: Genome editing - The zinc finger nucleases are intended to specifically cut the DNA within the albumin gene for insertion of a healthy factor IX gene. This cut site was chosen because it would not disrupt neighboring genes. If the factor IX gene was expressed, it may have the potential to produce healthy factor IX protein by the participant’s liver cells.
Outcome – The Sponsor collected and evaluated data from three similar genome editing clinical trials (FIXtendz was one of the trials). While the safety profile appeared favorable and there was evidence of activity, it was determined that it was unlikely that there was enough efficacy to provide clinical benefit to hemophilia B patients with the current doses being tested. The decision was made that no further subjects would be screened or dosed in the FIXtendz study. The study closed with only 1 participant treated. Due to the limited sample size, this study could not report any conclusions.
REC name
London - West London & GTAC Research Ethics Committee
REC reference
18/LO/0393
Date of REC Opinion
5 Jun 2018
REC opinion
Further Information Favourable Opinion