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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: BAY2599023 (DTX201)

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1756
    • SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD
• France
  • Paris, France, 75015
    • Hopital Necker les enfants malades - Paris
  • Rennes Cedex, France, 35033
    • Hopital Pontchaillou
• Germany
  • Berlin, Germany, 10249
    • Vivantes Klinikum Im Friedrichshain
  • Saarland
    • Homburg, Saarland, Germany, 66421
      • Universitätsklinikum des Saarlandes
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum (AMC)
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medisch Centrum
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202-3500
      • Arkansas Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C.S. Mott Children's Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin - Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Ultragenix pharmaceutical

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2018
• Primary Completion (Estimated): November 3, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: July 6, 2018
• First Submitted That Met QC Criteria: July 6, 2018
• First Posted (Actual): July 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Severe hemophilia A (<1% FVIII activity); Factor VIII gene therapy
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: 19429; 2017-000806-39 (EudraCT Number); 2023-505827-29-00 (Other Identifier: CTIS(EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No