Hemophilia A
Conditions
Interventions
Pharmaceutical Form:
Sponsors
Spark Therapeutics, Inc
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Able and willing to provide written informed consent 2. Males =18 years of age 3. Clinically severe hemophilia A, defined as: a. 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 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
Exclusion criteria
Exclusion criteria: 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 (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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this lead-in study is to establish the frequency of bleeding events in patients with severe hemophilia A receiving prophylactic or on demand infusions of factor VIII replacement therapy as standard of care. In addition, key characteristics of the bleeding events and FVIII infusions, as well as patient reported utcomes and medically important adverse events, will also be collected.;Secondary Objective: Not applicable;Primary end point(s): Efficacy Endpoints: • Number of bleeding events, annualized (Annualized bleeding rate [ABR]) • Location and severity of bleeds • Bleed type: spontaneous or traumatic • Number of treated and untreated bleeds • Number of bleeds into known any joints as well as bleeding into target joints, annualized • Number of prophylactic FVIII infusions per week • Dose and total FVIII consumption • Number of on-demand FVIII infusions required over the study duration • Annualized number of infusions (AIR) Safety Endpoints: • Incidence of medically important adverse events and serious adverse events Exploratory Endpoints: • Activities assessments • Quality-of-life assessments • Health-economic parameters;Timepoint(s) of evaluation of this end point: All participants will be included in all data summaries to the extent that a participant provides Screening visit data and data from at least one post-screening evaluation. Number of FVIII infusions per participant will be calculated, dose level and FVIII products as well as annual FVIII consumption and bleeding events per participant. These will be used to calculate the annualized infusion rate and annualized bleeding rate. The target joint assessments, level of activity, quality of life and health-economic parameters will be summarized according to recommendations and guidelines cited in the literature. In general, this consists of summarizing individual items scores and a total, mean or otherwise-defined composite score across all and/or a defined subset of | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, Finland, France, Germany, Ireland, Israel, Italy, South Africa, Sweden, Thailand, United Kingdom, United States
Contacts
Public ContactSr. Clinical Project Manager
Spark Therapeutics, Inc
Outcome results
None listed