A Factor IX Gene Therapy Study (FIX-GT)

Stopped early · Phase 1/Phase 2

Conditions studied: Hemophilia B

In brief

Severe haemophilia B (HB) is a bleeding disorder where a protein made by the body to help make blood clot is either partly or completely missing. This protein is called a clotting factor; with severe haemophilia B, levels of clotting factor IX (FIX) (nine) are very low and affected individuals can suffer life threatening bleeding episodes. HB mainly affects boys and men (normally one in every 30,000 males). Current treatment for HB involves intravenous infusions of factor IX as regular treatment (Prophylaxis) or 'on demand'. On demand treatment is highly effective at stopping bleeding but cannot fully reverse long-term damage that follows after a bleed. Regular treatment can prevent bleeding, however can be invasive for patients and also expensive. This research study aims to test the safety and effectiveness of a gene therapy which produces Factor IX protein in the body. The gene will be given using an inactivated virus called "the vector" ( FLT180a), in a single infusion. The vector has been developed from a virus known as an adeno- associated virus, that has been changed so that it is unable to cause a viral infection in humans. This "inactivated" virus is further altered to carry the Factor IX gene and to make its way within liver cells where Factor IX protein is normally made. Up to three different doses cohorts of FLT180a will be tested, in up to 24 patients with severe haemophilia B. Patients will be recruited from haemophilia centres in the EU and US. Patients will be in the trial for approximately 40 weeks and will undergo procedures including physical examinations, bloods tests, ECGs and liver ultrasounds.

Key facts

Study ID: NCT03369444
Run by: University College, London
People needed: 10
Starts: 2017-12-05
Expected to finish: 2020-10-20
Last updated by the study team: 2022-12-02

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

Adults males, ≥ 18 years of age.
Confirmed diagnosis of HB defined as one of the following:
Documented severe FIX deficiency with plasma FIX activity of <1% of normal, or
moderately severe FIX deficiency with plasma FIX activity level between ≥1% and ≤2% and a severe bleeding phenotype defined by one of the following: i. On prophylaxis for a history of bleeding, or ii. On demand therapy with a history of 4 or more bleeding episodes/year on average over the past 3 years, or iii. evidence of chronic haemophilic arthropathy (pain, joint destruction, and loss of range of motion).
Able to give full informed consent and able to comply with all requirements of the trial including 15-year long-term follow-up.
Willing to practice barrier contraception until at least 3 consecutive semen samples after vector administration are negative for vector sequences.
Lack of neutralising anti-AAV-S3 antibodies using an in vivo transduction inhibition assay within 4 weeks of vector administration.
At least 150 exposure days to FIX concentrates.

You may not qualify if…

Presence of neutralising anti-human FIX antibodies (inhibitor, determined by the Bethesda inhibitor assay) at the time of enrolment or a previous history of FIX inhibitor;
Patients at high risk of thromboembolic events (high risk patients would include those with a history of arterial or venous thromboembolism (e.g. deep vein thrombosis, pulmonary embolism, non-haemorrhagic stroke, arterial embolus) and those with acquired thrombophilia including conditions such as atrial fibrilation);
Use of investigational therapy for haemophilia within 30 days before enrolment;
Patients with active hepatitis B or C, and hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) Ribonucleic acid (RNA) viral load positivity, respectively, or currently on antiviral therapy for hepatitis B or C. Negative viral assays in 2 samples, collected at least 6 months apart, will be required to be considered negative. Both natural clearers and those who have cleared HCV on antiviral therapy are eligible.;
Serological evidence of human immunodeficiency virus (HIV-1);
Evidence of liver dysfunction (persistently elevated alanine aminotransaminase, aspartate aminotransferase, bilirubin >1.5 x upper limit of normal);
Platelet count <50 x 109/L;
Uncontrolled glaucoma, diabetes mellitus, or hypertension;
Malignancy requiring treatment;
Patients with uncontrolled cardiac failure, unstable angina or myocardial infarction in the past 6 months;
Poor performance status (World Health Organization score >1);
Prior treatment with any gene transfer medicinal product;
Known or suspected intolerance, hypersensitivity or contraindication to the investigational product and non-investigational medicinal products or their excipients;
Planned major elective surgery prior to the end of trial.
Current or relevant history of a physical or psychiatric illness or any medical condition that in the opinion of the investigator could affect the patients safety or interfere with the study assessments.
Cytomegalovirus (CMV) Immunoglobulin G (IgG) positive patients who are CMV PCR positive at screening.

Where it is running

St Jude Children's Research Hospital — Memphis, Tennessee, United States
St James's Hospital — Dublin, Ireland
University of Milan — Milan, Italy
Basingstoke Haemostasis and Thrombosis Centre — Basingstoke, United Kingdom
East Kent Hospitals University — Canterbury, United Kingdom
Guy's and St Thomas's NHS Foundation Trust — London, United Kingdom
Royal Free Hospital — London, United Kingdom
Newcastle Hospitals NHS Trust — Newcastle upon Tyne, United Kingdom
Oxford University Hospital — Oxford, United Kingdom
University of Sheffield — Sheffield, United Kingdom
University Hospital Southampton — Southampton, United Kingdom

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.