An observational Study in Males with Hemophilia A
- Conditions
- Hemophilia ATherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-000447-26-FI
- Lead Sponsor
- Spark Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 50
1. Able and willing to provide written informed consent
2. Males =18 years of age
3. Clinically severe hemophilia A, defined as:
a. <1% (<1 IU/dL) endogenous FVIII activity levels as documented by a certified laboratory; OR
b. 1-2% (1-2 IU/dL) endogenous FVIII activity levels and > 10 bleeding events per year
(in the last 52 weeks prior to screening); OR
c. 1-2% (1-2 IU/dL) endogenous FVIII activity levels and on regular continuous prophylaxis, defined as the intent to treat for 52 weeks/year and receiving a minimum of an a priori defined frequency of infusions for at least 45 weeks (85%) of the year under consideration
4. Participants on a prophylaxis regimen must have been on FVIII replacement therapy for a minimum of 2 months prior to Screening with the intention to remain on trophylaxis regimen for the
duration of the study
5. Previous exposure to FVIII therapy (i.e., = 150 documented exposure days to a FVIII protein product such as recombinant, plasmaderived or extended half-life FVIII product)
6. No prior history of hypersensitivity or anaphylaxis associated with any FVIII or intravenous immunoglobulin administration
7. No measurable inhibitor against FVIII at Screening or within the past 24 months, (i.e., < 0.6 Bethesda Units); no confirmed history of clinically significant FVIII inhibitor and no clinical signs or symptoms of decreased response to FVIII administration (Note: Family history of inhibitors is not exclusionary, nor will documentation of a single measurement of Bethesda titer of >0.6 BU that is not accompanied by clinical evidence of failure to respond to infused FVIII concentrate)
8. Willing to consider participation and treatment in a future Spark hemophilia A gene therapy study.
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1. Documented active hepatitis B or C within the past 12 months of Screening, as defined by:
a. Hepatitis B with positive results of Hepatitis B surface Antigen (HBsAg) or detectable HBV-DNA viral load.
i. Participants with positive HBsAB (evidence of vaccination) or positive HBcAB (previous exposure to Hep B virus) with a negative viral load are eligible
b. Documented hepatitis C positive antibody (anti-HCV) with a detectable HCV-RNA viral load.
i. Subjects with a negative anti-HCV or positive anti-HCV with a negative HCV-RNA viral load are eligible
All participants, except for those with historical results within the past 12 months of screening, will be required to undergo a diagnostic valuation of hepatitis status to participate in the study.
2. Currently on antiviral therapy to treat their hepatitis B or C;
3. Documented diagnoses of significant liver disease within the past 6 months of
screening, as defined by:
• Portal hypertension, or
• Chronic, persistent splenomegaly or
• Hepatic encephalopathy, or
Any participant without any of the pre-existing diagnoses above must have performed
either a Fibroscan or a combination of Fibrotest & APRI, within 6 months prior to
screening or at Screening:
i. FibroScan, with a score >8.8kPa units
ii. FibroTest/FibroSURE with a result >0.48
iii. AST-Platelet Ratio Index (APRI) >1).
4. Have serological evidence of HIV-1 or HIV-2 with CD4 counts =200/mm3.
a. Participants who are HIV-positive and on current antiretroviral drug regimen for
12 weeks, with a CD4 count (>200/mm3) and undetectable viral load (<50 gc/mL) at Screening, are eligible to enroll;
b. Participants who are HIV-negative with historical results within 12 months prior to Screening will not be required to undergo diagnostic evaluation of HIV status to participate in the study.
c. Participants without historical results within 12 months of screening will be required to undergo HIV screening to determine their HIV status prior to participation in the study.
5. Anti-AAV-Spark 200 neutralizing antibody titers >1:1;
6. Previously received a Sparkhemophilia A gene therapy product
7. Previously dosed with any investigational or approved gene therapy product at any time
8. Previously treated with an investigational drug within the last 12 weeks;
9. Planned surgical procedure in the next 12 months requiring FVIII prophylactic
treatment.
10. Any history of chronic infection or other chronic disease, concurrent clinically significant major disease (such as liver abnormalities or type I diabetes) including active malignancy, except for non-melanoma skin cancer, any other condition or any other unspecified reasons that, in the opinion of the Investigator or Sponsor, makes the participant unsuitable for participation and dosing in a future clinical study for Spark's hemophilia A gene therapy.
11. Unable or unwilling to comply with the schedule of visits and/or study assessments described in the clinical protocol.
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