Status:
TERMINATED
A Factor IX Gene Therapy Study (FIX-GT)
Lead Sponsor:
University College, London
Conditions:
Hemophilia B
Eligibility:
MALE
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
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 ...
Detailed Description
This was a Phase I/II, open-label, multicentre, ascending single-dose, safety study of FLT180a in patients with severe (FIX activity \<1%) or moderately severe (FIX activity 1% to 2% with severe bleed...
Eligibility Criteria
Inclusion
- 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.
Exclusion
- 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.
Key Trial Info
Start Date :
December 5 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
October 20 2020
Estimated Enrollment :
10 Patients enrolled
Trial Details
Trial ID
NCT03369444
Start Date
December 5 2017
End Date
October 20 2020
Last Update
December 2 2022
Active Locations (11)
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1
St Jude Children's Research Hospital
Memphis, Tennessee, United States, 38119
2
St James's Hospital
Dublin, Ireland
3
University of Milan
Milan, Italy
4
Basingstoke Haemostasis and Thrombosis Centre
Basingstoke, United Kingdom