A Study of BAX 888 in Male Adults With Severe Hemophilia A

Inclusion Criteria

• Male, aged 18 to 75 years at the time of screening.
• Established severe hemophilia A (FVIII: C =5 days without FVIII treatment) and/or documented intron 1 inversion or intron 22 inversion mutation in the F8 gene, consistent with severe hemophilia A , and documented evidence of >=3 hemorrhages over the previous 12 months requiring treatment with exogenous FVIII or use of FVIII prophylaxis because of history of frequent bleeding episodes.
• History of greater than (>) 150 exposure days to exogenously administered FVIII concentrates or cryoprecipitate.
• Sexually active men must agree to use barrier contraception (combination of a condom and spermicide) or limit sexual intercourse to post-menopausal, surgically sterilized, or contraception-practicing partners for a minimum of 6 months after administration of BAX 888, or until BAX 888 genomes are no longer detected in the semen, whichever is sooner.
• Participant is willing and able to comply with the requirements of the protocol, including provision of semen samples, maintenance of a diary of bleeding episodes and FVIII protein use.
• Signed informed consent.

Exclusion Criteria

• Bleeding disorder(s) other than hemophilia A.
• Personal laboratory evidence of having developed inhibitors to FVIII protein at any time (>=0.6 Bethesda units [BU] on any single test).
• Documented prior allergic reaction to any FVIII product.
• Anti-Adeno-associated virus, serotype 8 (AAV8) neutralizing antibody titer >=1:5. Participants whose laboratory assessments are less than or equal to ( =40 (Inova QUANTA LiteTM Actin IgG enzyme-linked immunosorbent assay [ELISA]); values of 31 to 39 will be flagged as possibly abnormal and the Investigator and Medical Monitor will evaluate the participant for eligibility.
• Elevated anti-liver-kidney microsomal antibody type 1 (LKM1) titers.
• Total immunoglobulin G (IgG) >1.5*upper limit of normal (ULN).
• Antinuclear antibody (ANA) titer >1: 320; OR ANA titer >1:80 if demonstrated concurrently with alanine aminotransferase (ALT) that is >ULN.
• Active Hepatitis virus (Hepatitis C): As indicated by detectable hepatitis C virus (HCV) ribonucleic acid (RNA) by polymerase chain reaction (PCR).
• Hepatitis B: If surface antigen is positive.
• Seropositive for Human Immunodeficiency Virus (HIV).
• Receiving systemic antiviral and/or interferon therapy within 4 weeks prior to enrollment.
• Clinically significant infections (e.g. systemic fungal infections) requiring systemic treatment.
• Known immune disorder (including myeloma and lymphoma).
• Concurrent chemotherapy or biological therapy for treatment of neoplastic disease or other disorders.
• An absolute neutrophil count =0.48 (i.e., Metavir staging of F2 or greater). Of note, in participants with a known history of Gilbert's syndrome, a Fibrotest cannot be used for fibrosis testing.
• Total bilirubin >1.5*ULN and direct bilirubin >=0.5 milligram per deciliter (mg/dL).
• ALT or aspartate aminotransferase (AST) >1.0*ULN.
• Alkaline phosphatase (AP) >2.0*ULN.
• History of liver biopsy indicating moderate or severe fibrosis (Metavir staging of F2 or greater).
• History of ascites, varices, variceal hemorrhage, or hepatic encephalopathy.
• Any findings on screening ultrasound that would preclude the safe use of AAV gene therapy.
• Prothrombin time (PT) international normalized ratio (INR) >=1.4.
• Serum creatinine >1.5 mg/dL.
• Urine protein >30 mg/dL or >0.5 gram per day (g/day).
• Body mass index >38.
• Major surgery or an orthopedic surgical procedure planned within 6 months after enrollment.
• Acute or chronic disease that, in the opinion of the investigator, would adversely affect participant safety or compliance or interpretation of study results.
• Received an AAV vector previously or any other gene transfer agent in the previous 12 months prior to Study Day 0.
• Received an investigational intervention or participated in another clinical trial within 4 weeks prior to enrollment or with