Study to Test the Safety and How Well Patients With Severe Hemophilia A Respond to Treatment With BAY 2599023 (DTX 201), a Drug Therapy That Delivers a Healthy Version of the Defective Factor VIII Gene Into the Nucleus of Liver Cells Using an Altered, Non-infectious Virus (AAV) as a "Shuttle"

A Phase 1/2 Open-label Safety and Dose-finding Study of BAY2599023 (DTX201), an Adeno-associated Virus (AAV) hu37-mediated Gene Transfer of B-domain Deleted Human Factor VIII, in Adults With Severe Hemophilia A

In this study researchers want to gather more information about safety and effectiveness of BAY 2599023 (DTX201), a drug therapy that delivers the human factor VIII gene into the human body by use of a viral vector to treat the disease. By replacing the defective gene with a healthy copy the human body may produce clotting factor on its own. Hemophilia A is a bleeding disorder in which the human body does not have enough clotting factor VIII, a protein that controls bleeding. Researcher want to find the optimal dose of BAY 2599023 (DTX201) so that the body may produce enough clotting factor on its own.

Inclusion Criteria:

• Males age 18 years or older.
• Confirmed diagnosis of hemophilia A as evidenced by their medical history with plasma FVIII activity levels < 1% of normal or at screening.
• Have >150 exposure days (EDs) to FVIII concentrates (recombinant or plasma-derived).

If on prophylaxis, are required to be willing to stop prophylactic treatment at specified time points throughout the study or If on-demand: should have had > 4 bleeding events in the last 52 weeks

- Agree to use reliable barrier contraception.

Exclusion Criteria:

• History of allergic reaction to any FVIII product.
• Clinically relevant findings in the physical examination considered critical by the treating physician, including obesity with BMI > 35 kg/m*2
• Current evidence of measurable inhibitor against factor VIII, prior history of inhibitors to FVIII protein or clinical history suggestive of inhibitor.
• Evidence of active hepatitis B or C.
• Currently on antiviral therapy for hepatitis B or C.
• Significant underlying liver disease.
• Serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm*3; HIV+ and stable participants with CD4 count >200/mm*3 and undetectable viral load are eligible to enroll.
• Detectable antibodies reactive with AAVhu37capsid.
• Participant with another bleeding disorder that is different from hemophilia A (e.g., von Willebrand disease, hemophilia B).
• Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational product within the last 12 weeks.
• Known or suspected hypersensitivity or allergic reaction to trial product(s) or related FVIII products or any component of BAY2599023 (DTX201), or a contraindication to prednisolone