NCT02618915

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2015

Geographic Reach
3 countries

9 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 23, 2015

Completed
9 days until next milestone

First Posted

Study publicly available on registry

December 2, 2015

Completed
14 days until next milestone

Study Start

First participant enrolled

December 16, 2015

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 18, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 18, 2017

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

November 14, 2018

Completed
Last Updated

November 14, 2018

Status Verified

October 1, 2018

Enrollment Period

1.8 years

First QC Date

November 23, 2015

Results QC Date

October 16, 2018

Last Update Submit

October 16, 2018

Conditions

Hemophilia B

Keywords

gene therapyHemophilia B

Outcome Measures

Primary Outcomes (2)

  • Number of Participants With Adverse Events (AEs), Treatment-Related Adverse Events (TEAEs), and Serious AEs (SAEs)

    An AE was defined as any untoward medical occurrence in a participant enrolled into this study (from the time the participant signed the informed consent form until his or her exit from the study), regardless of its causal relationship to study treatment. A TEAE was defined as any event not present before exposure to study product or any event already present that worsened in severity or increased in frequency after exposure to study product.

    up to 52 weeks after dosing (Cohort 1) or 44 weeks after dosing (Cohort 2)

  • Change From Baseline in FIX Activity at Week 6

    Peak plasma level of FIX after IV administration as determined by the activated partial thromboplastin time (aPTT) clot-based assay. Change from baseline: postbaseline value - baseline value. For the change from baseline, only participants with a value at both baseline visit and the specific postbaseline visit were included.

    Baseline, Week 6

Secondary Outcomes (8)

  • Annualized Bleeding Rate

    Week 0 to Week 52

  • Change From Baseline in FIX Activity Over Time

    Baseline, Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal

  • Annualized FIX Replacement Therapy

    Week 0 to Week 52

  • Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors)

    Day 0 (predose), Weeks 6, 8, 16, 32, 40, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal

  • Number of Participants With Cell-Mediated Immune Response to FIX

    Day 0 (predose), Weeks 6, 8, 12, 16, 32, 40, 48, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal

  • +3 more secondary outcomes

Study Arms (2)

DTX101, Cohort 1

EXPERIMENTAL

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

Genetic: DTX101

DTX101, Cohort 2

EXPERIMENTAL

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

Genetic: DTX101

Interventions

DTX101GENETIC

solution for IV infusion

Also known as: non-replicating recombinant AAVrh10 encoding human FIX (hFIX), AAVrh10FIX
DTX101, Cohort 1DTX101, Cohort 2

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • History of significant liver disease (ie, portal hypertension).
  • Significant hepatic inflammation or cirrhosis.
  • Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  • 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.
  • Anti-AAVrh10 neutralizing antibody titer \> 1:5.
  • Participation (current or previous) in another gene therapy study.
  • Participation in another investigational medicine study within 3 months before screening.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Orthopaedic Institute for Children

Los Angeles, California, 90007, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

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

Ann Arbor, Michigan, 48109, United States

Location

Vanderbilt Hemostasis-Thrombosis Clinic

Nashville, Tennessee, 37232, United States

Location

Specialized Hospital for Active Treatment for Hematological Disease

Sofia, 1756, Bulgaria

Location

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

Basingstoke, Hampshire, RG24 9NA, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 40197980DERIVED

MeSH Terms

Conditions

Hemophilia B

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, InheritedBlood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesCoagulation Protein DisordersHemorrhagic DisordersGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, X-Linked

Limitations and Caveats

After review of the DTX101 Phase 1/2 clinical trial data, a decision was made to discontinue the development of DTX101. The discontinuation was not due to any safety concerns related to DTX101.

Results Point of Contact

Title
Medical Information
Organization
Ultragenyx Pharmaceutical Inc
Medinfo@ultragenyx.com
1-888-756-8657

Study Officials

  • Medical Director

    Ultragenyx Pharmaceutical Inc

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 23, 2015

First Posted

December 2, 2015

Study Start

December 16, 2015

Primary Completion

October 18, 2017

Study Completion

October 18, 2017

Last Updated

November 14, 2018

Results First Posted

November 14, 2018

Record last verified: 2018-10

Locations

BU(1)US(6)GB(2)