A phase 1 study to evaluate the safety and tolerability of AAV2/6 Factor IX gene therapy in patients with severe Haemophilia B

Phase 1

• Conditions: Severe Haemophilia B; MedDRA version: 20.0 Level: LLT Classification code 10018939 Term: Haemophilia B (Factor IX) System Organ Class: 100000004850; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-004805-42-GB
• Lead Sponsor: Sangamo Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-04
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 16

Inclusion Criteria

Inclusion Criteria
1. Signed informed consent
2. Male =18 years of age and older (adult cohort); Male 12-17 years of age (pediatric cohort)
3. Severe heamophilia B (native circulating FIX activity <1%, with or without cross reactive material)
4. FIX mutations confirmed by FIX genome sequencing
5. With 150 or more exposure days to FIX concentrates
6. Sexually active subject must agree to use double barrier contraceptive (one of them being a condom) or abstinence and all subjects must refrain from donating their sperm until at least 2 consecutive semen samples after SB-FIX are negative for AAV 2/6 and for a minimum of 90 days after SB-FIX administration
Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria
1. Presence of neutralizing antibodies to AAV 2/6
2. History of hypersensitivity response or allergic reaction to FIX or FIX products
3. Currently receiving long acting FIX replacement therapy and unwilling to switch to short acting FIX infusions
4. FIX mutations known to be associated with FIX inhibitors, including those with a large gene deletion
5. Polymorphisms in the ZFN target region of the albumin locus
6. Presence of any liver mass on MRI or equivalent imaging technology, or elevated alpha-fetoprotein (AFP)
7. Any contraindication to the use of corticosteroids for immunosuppression
8. Currently receiving antiviral therapy for hepatitis B or C or with history of active hepatitis B or hepatitis C or HIV-1 or HIV 1/2 antibody positive. To be considered HCV-negative after an active HCV infection, viral assays in two samples collected at least six months apart must be negative
9. Chronic anaemia, leukopenia, or thrombocytopenia
10. Past medical history of active tuberculosis or systemic fungal disease
11. Symptomatic cardiovascular disease as a co-morbid condition
12. Markers of hepatic inflammation or overt or occult cirrhosis as evidenced by one or more of the following:
• Albumin =3.5 g/dL (35g/L)
• Total bilirubin >1.5 x ULN and direct bilirubin =0.5 mg/dL (8.55 µmol/L)
• Alkaline phosphatase >2.0 x ULN
• ALT or AST >2.0 x ULN
13. History of chronic renal disease or creatinine = 1.5 mg/dL (133 µmol/L)
14. Systemic (iv or oral) immunomodulatory agent or steroid use (topical treatment is allowed, e.g. for asthma or eczema) within 3 months prior to Screening
15. History of chronic infection or other chronic disorder considered an unacceptable risk
16. History of malignancy except for treated basal cell or squamous cell carcinoma
17. History of alcohol or substance abuse
18. Previously received gene therapy product
19. Participation in prior investigational drug or medical device study within the previous 3 months
20. History of therapeutic non-adherence
21. Any other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for participation in the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified