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

NCT ID: NCT02618915

Last Updated: 2018-11-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-16
• Study Completion Date: 2017-10-18

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.

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.

This study was previously posted by Dimension Therapeutics, which has been acquired by Ultragenyx in November 2017.

Conditions

Hemophilia B

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DTX101, Cohort 1

a single peripheral intravenous (IV) infusion of 1.6 x 10\^12 genome copies (GC)/kg DTX101

Group Type: EXPERIMENTAL

DTX101

Intervention Type: GENETIC

solution for IV infusion

DTX101, Cohort 2

a single peripheral IV infusion of 5.0 x 10\^12 GC/kg DTX101

Group Type: EXPERIMENTAL

DTX101

Intervention Type: GENETIC

solution for IV infusion

Interventions

DTX101

solution for IV infusion

Intervention Type: GENETIC

Other Intervention Names

non-replicating recombinant AAVrh10 encoding human FIX (hFIX); AAVrh10FIX

Eligibility 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/mm^3, 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 polymerase chain reaction.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Ultragenyx Pharmaceutical Inc

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Orthopaedic Institute for Children

Los Angeles, California, United States

University of Florida

Gainesville, Florida, United States

Boston Children's Hospital

Boston, Massachusetts, United States

University of Michigan Hospital and Health Systems, Michigan Clinical Research Unit

Ann Arbor, Michigan, United States

Vanderbilt Hemostasis-Thrombosis Clinic

Nashville, Tennessee, United States

Specialized Hospital for Active Treatment for Hematological Disease

Sofia, , Bulgaria

Basingstoke and North Hampshire Hospital, Haemophilia, Haemostasis and Thrombosis Centre

Basingstoke, Hampshire, United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

United States; Bulgaria; United Kingdom

References

Pipe S, Poma A, Rajasekhar A, Everington T, Sankoh S, Allen J, Cataldo J, Crombez E. Gene therapy for hemophilia B: results from the phase 1/2 101HEMB01/02 studies. Blood Adv. 2025 Jun 24;9(12):2980-2987. doi: 10.1182/bloodadvances.2024015184.

Reference Type: DERIVED

PMID: 40197980 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

101HEMB01

Identifier Type: -

Identifier Source: org_study_id