A Factor IX Gene Therapy Study (FIX-GT)

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 24

Inclusion Criteria

1.Adults males, = 18 years of age;
2.Confirmed diagnosis of HB defined as one of the following:
(a)Documented severe FIX deficiency with plasma FIX activity of <1% of normal or
(b)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).
3.Able to give full informed consent and able to comply with all requirements of the trial including 15-year long-term follow-up;
4.Willing to practice barrier contraception until at least two consecutive semen samples after vector administration are negative for vector sequences;
5.Lack of neutralising anti-AAV-S3 antibodies using an in-vivo transduction inhibition assay within 4 weeks of vector administration;
6.At least 150 exposure days to FIX concentrates.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1.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;
2.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);
3.Use of investigational therapy for haemophilia within 30 days before enrolment;
4.Patients with active hepatitis B or C, and HBsAg or HCV 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.);
5. Serological evidence of HIV-1
6.Evidence of liver dysfunction (persistently elevated alanine aminotransaminase,
aspartate aminotransferase, bilirubin >1.5 x upper limit of normal);
7.Platelet count <50x109/L;
8.Uncontrolled glaucoma, diabetes mellitus, or hypertension;
9.Malignancy requiring treatment;
10.Patients with uncontrolled cardiac failure or unstable angina or myocardial infaction
in the past 6 months;
11.Poor performance status (World Health Organization score >1);
12.Prior treatment with any gene transfer medicinal product;
13.Known or suspected intolerance hypersensitivity or contraindicationto the
investigational product and non-investigational product or their excipients.
14.Planned major elective surgery prior to the end of trial.
15. Current or relevant history of a physical of psychiatric illness or any medical
condition that in the opinion of the investigator could affect the patients safety or
interfere with the study assessments.
16. CMV IgG postive patients who are CMV PCR positive at screening

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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