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".

• ClinicalTrials.gov Identifier: NCT03588299
• Recruitment Status: Active, not recruiting
• First Posted: July 17, 2018
• Last Update Posted: January 6, 2023
• Sponsor: Bayer
• Collaborator: Ultragenix pharmaceutical
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: July 6, 2018
• First Posted Date: July 17, 2018
• Last Update Posted Date: January 6, 2023
• Actual Study Start Date: November 7, 2018
• Estimated Primary Completion Date: November 3, 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 9, 2022): Number of patients with adverse events (AEs), treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and AEs/SAEs of special interest [ Time Frame: Up to 5 years ]
• Original Primary Outcome Measures (submitted: July 6, 2018): Number of patients with adverse events (AEs), treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and AEs/SAEs of special interest [ Time Frame: Up to 52 weeks ]

Current Secondary Outcome Measures (submitted: February 14, 2020)

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

Original Secondary Outcome Measures (submitted: July 6, 2018)

Change of FVIII activity from baseline throughout the study [ Time Frame: Up to 5 years ]

FVIII activity will be determined using both a one-stage assay and chromogenic assay.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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".
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemophilia A

Intervention

Drug: BAY2599023 (DTX201)

Single escalating doses with 4 dose steps; Single intravenous (IV) administration.

Study Arms

Experimental: BAY2599023 / (DTX201)

Adult patients with severe hemophilia A, who have been previously treated with FVIII products

Intervention: Drug: BAY2599023 (DTX201)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 12, 2022): 11
• Original Estimated Enrollment (submitted: July 6, 2018): 18
• Estimated Study Completion Date: November 30, 2026
• Estimated Primary Completion Date: November 3, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, France, Germany, Netherlands, United Kingdom, United States
• Removed Location Countries: Spain

Administrative Information

• NCT Number: NCT03588299
• Other Study ID Numbers: 19429; 2017-000806-39 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

• Current Responsible Party: Bayer
• Original Responsible Party: Same as current
• Current Study Sponsor: Bayer
• Original Study Sponsor: Same as current
• Collaborators: Ultragenix pharmaceutical
• Investigators: Not Provided
• PRS Account: Bayer
• Verification Date: January 2023