A phase 1/2 open-label safety and dose-finding study of BAY 2599023 (DTX201), an adeno-associated virus (AAV) hu37-mediated gene transfer of B-domain deleted human factor VIII, in adults with severe hemophilia A

• Males >= 18 years of age, • Subjects with severe hemophilia A (baseline FVIII
activity FVIII:C <1%), • Previously treated with FVIII concentrate(s) (plasma
derived or recombinant) or cryoprecipates for a minimum of 150 exposure days
(ED), • Are on one of the following therapies: Prophylaxis, and is able and
willing to stop prophylactic treatment at specified time points throughout the
study or On-demand: have had > 4 bleeding events in the last 52 weeks, •
Subjects must agree to use double barrier and effective contraception methods.
Vasectomized subjects must agree to use condoms. This is applicable from the
time of the study drug administration until notified by the investigator. Time
until discontinuation of contraception will be at a minimum of 6 months, and
will progressively increase with increasing dose. Recommendation to
investigators is to continue the contraception until three consecutive blood
and semen samples BLOD of shed virus have been obtained. Acceptable methods of
contraception include, but are not limited to, (i) condoms with a spermicidal
agent (ii) diaphragm or cervical cap with spermicide; if an intra-uterine
device or hormone-based contraception is used by the patient*s partner, an
additional barrier method must be used., • Male subjects must agree not to
donate cells, semen, blood, tissue or organs from the time of study drug
administration.

• Current evidence of inhibitor to FVIII with a titer >= 0.6 BU/mL • History of
inhibitor to FVIII with a titer >= 0.6 BU, or clinical history suggestive of
inhibitor requiring modification of treatment . Family history of inhibitors
will not exclude the subject• Have significant underlying liver disease as
evidenced by any of the following: portal hypertension, splenomegaly, ascites,
esophageal varices, hepatic encephalopathy, reduction below normal limits of
serum albumin or a liver biopsy with evidence of stage 3 fibrosis, • Any of the
following: Hemoglobin <11 g/dL; Platelets <100,000
cells/µL; Aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) >1.5 × ULN; Alkaline phosphatase (AP) >2.5 × ULN; Total bilirubin
>1.5 × ULN; Prothrombin time (PT) or international normalized ratio
(INR) >1.0 × ULN; Serum creatinine >1.5 mg/dL • Have active hepatitis B or C
infection, as reflected by HBsAg or HCV-RNA viral load positivity, • Currently
on antiviral therapy for hepatitis B or C., • Serological evidence of active
HIV-1 or HIV-2 as measured by CD4+ cell count <200 cells/mm3 and a viral load
>50 gc/mL • Anti-AAVhu37 neutralizing antibody titer >=1:5, • Any major and/or
orthopedic surgery within screening period prior to trial product
administration, and at least 6 months thereafter, • History of a malignancy for
which the subject has received treatment in the past 2 years except for
prostate cancer being monitored without medical intervention, or surgically
removed non-melanoma skin cancer, • Known or suspected autoimmune diseases, •
Known prior history of hypersensitivity or anaphylaxis associated with any
FVIII or immunoglobulin administration., • Known or suspected hypersensitivity
or allergic reaction to trial product(s) or related FVIII products or any
component of BAY 2599023 (DTX201), or a contraindication
to prednisolone (as of amendment 6) • Live vaccines and COVID-19 vaccines
within the last 30 days prior to the study drug administration; live vaccines
may be re-introduced after viral shedding has been cleared , • Subjects on
treatment with immunomodulatory agents within the last 3 months prior to study
entry or during the study, • Any individual who requires any pre-medication to
tolerate FVIII treatment (e.g., antihistamines), • Prior use of emicizumab
within 3 months before dosing, • Clinically relevant findings in the physical
examination considered critical by the treating physician, including obesity
with BMI > 35 kg/m2. •