A Gene Therapy Study of SPK-8011QQ in Adults With Severe or Moderately Severe Hemophilia A

Inclusion Criteria20

• Signed Informed Consent Form (ICF)
• ≥18 years of age at the time of signing the ICF
• Male sex assigned at birth
• Severe or moderately severe hemophilia A, defined as endogenous FVIII:C activity levels ≤3%, as documented (historically or during the Screening Period) by a certified laboratory and where the FVIII:C level is measured more than 96 hours after the prior dose of an extended half-life FVIII replacement product or more than 72 hours after the prior dose of a standard half-life FVIII replacement product
• Have documented treatment for a minimum of 6 months prior to screening with either of the following: plasma coagulation factor VIII (FVIII) prophylaxis, defined as receiving a prescribed dose and frequency of FVIII infusions with the intent to treat continuously for 52 weeks per year; or FVIII on demand, with a history of ≥ 5 breakthrough bleeds in the 6 months prior to screening
• No prior history of hypersensitivity or anaphylaxis associated with the administration of any FVIII product
• Have ≥150 exposure days to a FVIII protein product such as recombinant, plasma-derived, or extended half-life FVIII product
• Negative screening test for inhibitor against FVIII (i.e., <0.6 BU)
• Candidates with prior FVIII inhibitors who are tolerized having completed successful ITI at least 5 years before screening are eligible provided they have had no evidence of inhibitor recurrence (permanent or temporary) within 5 years prior to screening as may be indicated by detection of an inhibitor, FVIII half-life <6 hours, or FVIII recovery <66% since completing ITI
• Confirmed negative anti-Spark200 antibodies as documented through central laboratory testing of a serum sample
• Acceptable hepatobiliary function according to all of the following criteria: ALT, AST, and ALP ≤2×ULN and INR <1.4 at the time of screening; No evidence of cirrhosis or advanced liver disease on screening liver ultrasound; Otherwise no laboratory or clinical evidence of liver disease or cirrhosis, per the Investigator's judgement
• Adequate renal function, defined as creatinine clearance ≥30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration formula; patients on dialysis are not eligible for the study
• Platelet count ≥50,0000 cells/µL
• Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on an antiretroviral treatment regimen, have a cluster of differentiation (CD4) count >200/mm3, and undetectable viral load (<50 gc/mL)
• Negative hepatitis B surface antigen (HBsAg) at screening
• Positive hepatitis surface antibody (HBsAb) at screening, or a negative HBsAb at screening accompanied by either of the following: Negative hepatitis B core antibody (HBcAb); Positive HBcAb and negative hepatitis B virus (HBV) DNA test
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test at screening accompanied by negative HCV RNA test
• Otherwise appropriate medical history and physical and laboratory evaluation that are acceptable for inclusion in this clinical trial
• Are able and willing to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of applicable patient-reported outcome questionnaires
• Agreement to adhere to the contraception requirements described in the protocol