Study of a Gene Therapy Treatment for Hemophilia A

Inclusion Criteria: * Have a negative anti-AAV-Spark200 neutralizing antibody (NAb) test result. * Are adult males with severe or moderately severe hemophilia A, defined as endogenous FVIII activity ≤3%, as documented by a certified laboratory (historically or during the Screening Period) and where the FVIII:C level is measured more than 96 hours after the prior dose of an extended-half-life FVIII * Have ≥150 documented exposure days to an FVIII protein product such as recombinant, plasma-derived, or extended half-life FVIII product * Have no prior history of hypersensitivity or anaphylaxis associated with the administration of any FVIII product. * Have screening hepatic ultrasound without evidence of cirrhosis and no laboratory or clinical evidence per the Investigator's judgment of advanced liver disease or cirrhosis. * Have a negative test for inhibitor against FVIII (ie, \<0.6 Bethesda units \[BU\]) during screening. * Have no documented FVIII inhibitor (ie, \<0.6 BU), FVIII half-life \<6 hours, or FVIII recovery \<66% in the 5 years prior to screening. * Candidates who completed successful immune tolerance induction (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. * If human immunodeficiency virus (HIV)-positive at screening, have an adequate cluster of differentiation 4 (CD4) count (\>200/mm3) and undetectable viral load (\<50 genome copies \[gc\]/mL), are on an antiretroviral drug regimen, and have completed at least 12 weeks of this treatment regimen prior to screening. * Meet the following inclusion criteria by cohort: * Cohort A: have documented history of prior treatment with FVIII prophylaxis (defined as receiving a prescribed dose and frequency of FVIII infusions with the intent to treat continuously for 52 weeks per year) for a minimum of 6 months prior to screening; and are willing to continue their FVIII prophylaxis during the Lead-In Period of this study (minimum of 24 weeks). * Cohort B: have documented history of prior treatment with FVIII on demand for a minimum of 6 months that shows ≥5 treated bleeds in the last 6 months prior to screening. * Cohort C: have documented history of prior treatment with emicizumab prophylaxis for a minimum of 6 months prior to screening. Exclusion Criteria: * Have an inherited or acquired bleeding disorder other than hemophilia A * Have inherited or acquired thrombophilia, have signs of thromboembolic disease in the Investigator's judgment, or are on current treatment for thromboembolic disease. A history of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing is not considered an exclusion criterion. * Have concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the Investigator or Sponsor, preclude the candidate's safe participation in and completion of the study, or the interpretation of the study results.