Severe Haemophilia B MedDRA version: 20.0 Level: LLT Classification code 10018939 Term: Haemophilia B (Factor IX) System Organ Class: 100000004850
Conditions
Interventions
Product Name: rAAV2/6 Left ZFN Vector
Product Code: SB-42906
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not yet assigned
Sponsors
Sangamo Therapeutics, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary: 1. Changes in FIX antigen and FIX activity levels from baseline over time 2. Change from baseline in the number of FIX units infused per week 3. Change from baseline in number and severity of bleeding episodes 4. Changes in neutralizing antibodies to FIX from baseline over time 5. Presence and shedding of AAV2/6 vector DNA, by PCR in plasma, saliva, urine, stool, and semen over time ; Timepoint(s) of evaluation of this end point: 1. FIX antigen: Baseline (BL), Day 1, Day 7, Wks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, Months 15, 18, 21, 24, 27, 30, 33, 36 (EOS) & Early Termination Visit 2. FIX activity: BL, Day 1, Day 7, Weekly (Wk 2-Wk 12), Wk 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, Months 15, 18, 21, 24, 27, 30, 33, 36 & Early Termination Visit 3. Bleeding episodes & FIX concentrates usage: From BL through end of the study including early termination visit 4. FIX inhibitor level: BL, Day 1, Wks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, Months 15, 18, 21,24, 27, 30, 33, 36 & Early Termination Visit 5. Presence & shedding in AAV2/6 vector DNA by PCR in plasma, saliva, urine, stool & semen over time: BL, Day 1, Day 7, WKs 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 & Early termination visit | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the safety and tolerability of SB-FIX.; Secondary Objective: 1. Change from baseline in FIX antigen and activity levels 2. Change from baseline in use of Factor IX replacement therapy 3. Change from baseline in frequency and severity of bleeding episodes 4. Immune response to FIX 5. Presence and shedding of AAV2/6 vector DNA by PCR in plasma, saliva, urine, stool and semen ; Primary end point(s): Primary: Safety and tolerability will be assessed by the grading of AEs/SAEs and change in laboratory evaluations from baseline ; Timepoint(s) of evaluation of this end point: 1) AE assessment Baseline, Day 0, Day 1, Day 7, weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, months 15, 18, 21,24, 27, 30, 33, 36 (EOS) & Early Termination Visit 2) Laboratory evaluations -CBC: Baseline, Day 0, Day 1, weeks 4, 8, 12, 28,52, months 15, 18, 21,24, 27, 30, 33, 36/EOS & Early Termination Visit -Serum Chemistry, Metabolic Panel: All time points except day 7 -Coagulation screen: Baseline, Day 0, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, months 15, 18, 21,24, 27, 30, 33, 36/EOS & Early Termination Visit -Liver Panel: Tested twice per week from baseline through week 12, then tested at wks 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, months 15, 18, 21, 24, 27, 30, 33, 36/EOS & early termination | — |
Countries
United Kingdom, United States
Contacts
Public ContactSB-FIX-1501 Information Desk
Sangamo Therapeutics, Inc.
Outcome results
None listed