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 \<1%, measured following \>=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 (\<=) 1:10 may be re-tested within the same screening window and, if eligibility criterion is met on retest, may be enrolled after confirmation by the Sponsor Medical Monitor. * Known hypersensitivity to prednisolone or prednisone, or to any of the excipients. * Having a disease in which treatment with prednisolone or prednisone is not tolerated (including but not limited to osteoporosis with vertebral fractures, difficult to control hypertension, and difficult to control diabetes). * Evidence of markers of potential underlying risk for autoimmune mediated hepatic disease: * Anti-smooth muscle antibody assay results \>=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 \<1000 cells per cubic millimeter (cells/mm\^3). * Markers of hepatic inflammation or cirrhosis as evidenced by 1 or more of the following: * Platelet count of \<150,000/microliter (mcL). * Serum albumin level is below the central laboratory's lower limit of normal and FibroSURE is \>=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 within 5 half-lives of the investigational drug administration, whichever is longer. * Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease). * Recent history of psychiatric illness or cognitive dysfunction (including drug or alcohol abuse) that in the opinion of the investigator, is likely to impair participants ability to comply with protocol mandated procedures. * Participant is a family member or employee of the investigator.