Study to Evaluate the Efficacy and Safety of Valoctocogene Roxaparvovec, With Prophylactic Steroids in Hemophilia A

Inclusion Criteria

• Males >= 18 years of age with hemophilia A and residual FVIII levels 200/mm^3 and an undetectable viral load (unquantifiable viral load as defined as less than the limit of quantification by the testing laboratory's assay is permitted) while receiving an antiretroviral therapy (ART) regimen that does not contain efavirenz or another potentially hepatotoxic ART.
• Significant liver dysfunction with any of the following abnormal laboratory results: alanine aminotransferase (ALT) > 1.25x upper limit of normal (ULN);aspartate aminotransferase (AST) > 1.25x ULN;gamma-glutamyltransferase (GGT) > 1.25x ULN;Total bilirubin > 1.25x ULN;Alkaline phosphatase > 1.25x ULN; or international normalized ratio (INR) >= 1.4.

Participants whose liver laboratory assessments fall outside of these ranges could undergo repeat testing of the entire liver test panel within the same Screening window and, if eligibility criteria are met on retest, could be enrolled after confirmation by the Medical Monitor.

• FibroScan or prior liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0-4 on the Batts-Ludwig (Batts 1995) or METAVIR (Bedossa 1996) scoring systems, or an equivalent grade of fibrosis if an alternative scale is used.
• Evidence of any bleeding disorder not related to hemophilia A.
• Platelet count of = 1.5 mg/dL
• Liver cirrhosis or other clinically significant liver disease of any etiology as assessed by FibroScan or liver ultrasound.
• Chronic or active hepatitis B as evidenced by positive serology testing (hepatitis B surface antigen [HBsAg], hepatitis B surface antibody [HBsAb], and hepatitis B core antibody [HBcAb]) and confirmatory hepatitis B virus (HBV) DNA testing. Refer to the Centers for Disease Control (CDC) table for the interpretation of serological test results in the Laboratory Manual.
• Active Hepatitis C as evidenced by detectable hepatitis C virus (HCV) RNA or currently on antiviral therapy.
• Active malignancy, except non-melanoma skin cancer.
• History of hepatic malignancy.
• History of arterial or venous thromboembolic events (eg, deep vein thrombosis, non-hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolus), with the exception of catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing.
• Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation.
• Treatment with any investigational product within 30 days or 5 half-lives of the investigational product prior to the screening period. For participants who have received a prior investigational product, all ongoing adverse events (AEs) experienced while receiving that investigational product must have resolved prior to screening for this study.
• Any condition that, in the opinion of the Investigator or Sponsor would prevent the patient from fully complying with the requirements of the study (including possible corticosteroids (CS) treatment and/or use of alternative immunosuppressive agents (AIS) outlined in the protocol) and/or would impact or interfere with evaluation and interpretation of participant safety or efficacy result.
• Prior treatment with any vector or gene transfer agent.
• Major surgery planned in the 52-week period following the infusion with BMN 270.
• Use of systemic immunosuppressive agents, not including CS, or live vaccines within 30 days before the BMN 270 infusion.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study that does not interfere with the requirements of the current protocol or have the potential to impact the evaluation of efficacy and safety of BMN 270 and with prior consultation with the Medical Monitor.
• Known allergy or hypersensitivity to BMN 270 investigational product formulation.
• Unwilling to receive blood or blood products for treatment of an adve