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Safety and Dose Finding Study of DTX101 (AAVrh10FIX) in Adults With Moderate/Severe to Severe Hemophilia B

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ClinicalTrials.gov Identifier: NCT02618915
Recruitment Status : Completed
First Posted : December 2, 2015
Last Update Posted : November 1, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
A Phase 1/2, open-label, dose-finding safety study of single ascending doses of DTX101 in adult males with moderate/severe to severe hemophilia B.

Condition or disease Intervention/treatment Phase
Hemophilia B Genetic: AAVrh10FIX Phase 1 Phase 2

Detailed Description:

Hemophilia B is an X-linked recessive genetic bleeding disorder caused by mutations in the factor IX (FIX) gene. FIX is produced in the liver and is critical for fibrin clot formation. Hemophilia B is characterized by frequent, spontaneous internal bleeding that can lead to chronic arthropathy (joint damage), intracranial hemorrhage, and even death. In patients with moderate/severe to severe hemophilia B, the majority of bleeding episodes occur in the joints and, if not treated, lead to debilitating damage and a decreased quality of life.

This study will evaluate the safety and efficacy of the adeno-associated virus (AAV) to deliver human factor IX (hFIX) gene, the healthy gene necessary to make FIX, to the liver where FIX is normally produced. This study will determine if AAVrh10 can produce clinically meaningful FIX levels in patients with moderately/severe or severe hemophilia B.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Open-Label Safety and Dose Finding Study of Adeno-Associated Virus (AAV) rh10-Mediated Gene Transfer of Human Factor IX in Adults With Moderate/Severe to Severe Hemophilia B
Study Start Date : November 2015
Primary Completion Date : October 2017
Study Completion Date : October 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Dose 1
1.6 x 10^12 GC/kg DTX101(AAVrh10FIX)
Genetic: AAVrh10FIX
non-replicating recombinant AAVrh10 encoding human FIX (hFIX)
Other Name: DTX101
Experimental: Dose 2
3.0 x 10^12 GC/kg DTX101 (AAVrh10FIX)
Genetic: AAVrh10FIX
non-replicating recombinant AAVrh10 encoding human FIX (hFIX)
Other Name: DTX101
Experimental: Dose 3
5.0 x 10^12 GC/kg DTX101 (AAVrh10FIX)
Genetic: AAVrh10FIX
non-replicating recombinant AAVrh10 encoding human FIX (hFIX)
Other Name: DTX101
Experimental: Dose 4
1.0 x 10^13 GC/kg DTX101 (AAVrh10FIX)
Genetic: AAVrh10FIX
non-replicating recombinant AAVrh10 encoding human FIX (hFIX)
Other Name: DTX101


Outcome Measures

Primary Outcome Measures :
  1. The incidence of treatment-related adverse events by dosing group [ Time Frame: 52 weeks ]
  2. Change from baseline in FIX activity level [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Number of Bleeding Episodes requiring recombinant FIX infusion [ Time Frame: 52 weeks ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male ≥18 years of age.
  2. Moderate/severe or severe hemophilia B (baseline FIX activity ≤2% of normal or documented history of FIX activity ≤2%).
  3. At least 3 bleeding episodes per year that require on-demand treatment with FIX OR are treated with a prophylactic regimen of FIX.
  4. At least 100 days exposure history to FIX.
  5. No documented history of inhibitors (neutralizing antibodies) to exogenous FIX.
  6. No known allergic reaction to exogenous FIX or any component of DTX101.
  7. Willing to stop prophylactic treatment with recombinant FIX at specified time points during the study.

Exclusion Criteria:

  1. History of significant liver disease (ie;portal hypertension).
  2. Significant hepatic inflammation or cirrhosis.
  3. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  4. History of human immunodeficiency virus (HIV) infection AND any of the following: CD4+ cell count <350 cells/mm3, change in antiretroviral therapy regimen within 6 months prior to Day 0, or plasma viral load >200 copies/mL, on 2 separate occasions, as measured by PCR.
  5. Anti-AAVrh10 neutralizing antibody titer >1:5.
  6. Participation (current or previous) in another gene therapy study.
  7. Participation in another investigational medicine study within 3 months before screening.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02618915


Locations
United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, California
Orthopaedic Institute for Children
Los Angeles, California, United States, 90007
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Hospital and Health Systems, Michigan Clinical Research Unit
Ann Arbor, Michigan, United States, 48109
United States, Tennessee
Vanderbilt Hemostasis-Thrombosis Clinic
Nashville, Tennessee, United States, 37232
Bulgaria
Specialized Hospital for Active Treatment for Hematological Disease
Sofia, Bulgaria, 1756
United Kingdom
Basingstoke and North Hampshire Hospital, Haemophilia, Haemostasis and Thrombosis Centre
Basingstoke, Hampshire, United Kingdom, RG24 9NA
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Dimension Therapeutics
Investigators
Study Director: Allen Poma, MD Dimension Therapeutics
More Information

Responsible Party: Dimension Therapeutics
ClinicalTrials.gov Identifier: NCT02618915     History of Changes
Other Study ID Numbers: 101HEMB01
First Posted: December 2, 2015    Key Record Dates
Last Update Posted: November 1, 2017
Last Verified: October 2017

Keywords provided by Dimension Therapeutics:
gene therapy
Hemophilia B

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked