Clinical trial NCT03588299: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hemophilia A
Keywords: Severe hemophilia A (<1% FVIII activity)
Factor VIII gene therapy
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Ultragenix pharmaceutical
First posted: 2018-07-17
Enrollment: 11
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of patients with adverse events (AEs), treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and AEs/SAEs of special interest
timeFrame: Up to 5 years.
Secondary outcomes:
measure: Expression pattern of FVIII activity.
timeFrame: Up to 5 years
measure: Proportion of patients in the respective dose step, that reached an expression of FVIII above 5%
timeFrame: At 6 months and 12 months following the IV administration of BAY2599023
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital - Hematology / Oncology
state: Arkansas
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital - Hematology / Oncology
state: Michigan
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Sofia
country: Bulgaria
facility: SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD
city: Paris
country: France
facility: APHP-Hopital Necker Enfants malades
city: Rennes Cedex
country: France
facility: CHU Rennes - Hopital Pontchaillou
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
state: Saarland
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum (AMC)
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
Study officials:
References: