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.

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hemophilia A

Intervention / Treatment
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* Drug: BAY2599023 (DTX201)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY2599023 / (DTX201)<br>Adult patients with severe hemophilia A, who have been previously treated with FVIII products | Drug: BAY2599023 (DTX201)<br>* Single escalating doses with 4 dose steps; Single intravenous (IV) administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events (AEs), treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and AEs/SAEs of special interest |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression pattern of FVIII activity. | Determined using both a one-stage assay and chromogenic assay. | Up to 5 years | 
| Proportion of patients in the respective dose step, that reached an expression of FVIII above 5% |  | At 6 months and 12 months following the IV administration of BAY2599023 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe hemophilia A (<1% FVIII activity), Factor VIII gene therapy