Safety and Dose Finding Study of DTX101 (AAVrh10FIX) in Adults With Moderate/Severe to Severe Hemophilia B
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02618915|
Recruitment Status : Terminated (Sponsor decision; not due to any safety concerns related to DTX101.)
First Posted : December 2, 2015
Results First Posted : November 14, 2018
Last Update Posted : November 14, 2018
|Condition or disease||Intervention/treatment||Phase|
|Hemophilia B||Genetic: DTX101||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||December 16, 2015|
|Actual Primary Completion Date :||October 18, 2017|
|Actual Study Completion Date :||October 18, 2017|
Experimental: DTX101, Cohort 1
a single peripheral intravenous (IV) infusion of 1.6 x 10^12 genome copies (GC)/kg DTX101
solution for IV infusion
Experimental: DTX101, Cohort 2
a single peripheral IV infusion of 5.0 x 10^12 GC/kg DTX101
solution for IV infusion
- Number of Participants With Adverse Events (AEs), Treatment-Related Adverse Events (TEAEs), and Serious AEs (SAEs) [ Time Frame: up to 52 weeks after dosing (Cohort 1) or 44 weeks after dosing (Cohort 2) ]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.
- Change From Baseline in FIX Activity at Week 6 [ Time Frame: Baseline, 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.
- Annualized Bleeding Rate [ Time Frame: Week 0 to Week 52 ]The number of bleeding episodes per participant was recorded, and the annualized number of bleeding episodes was calculated.
- Change From Baseline in FIX Activity Over Time [ Time Frame: 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 ]Peak plasma level of FIX after IV administration as determined by the 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. Participants were not required to stop prophylactic treatment with recombinant FIX until after Week 4 and may have been restarted on their prophylactic recombinant FIX treatment after Week 14.
- Annualized FIX Replacement Therapy [ Time Frame: Week 0 to Week 52 ]The use of on-demand FIX replacement therapy was recorded by dose (IU/kg) administered, and the annualized use of FIX replacement therapy was calculated. Participants were not required to stop prophylactic treatment with recombinant FIX until after Week 4 and may have been restarted on their prophylactic recombinant FIX treatment after Week 14.
- Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) [ Time Frame: Day 0 (predose), Weeks 6, 8, 16, 32, 40, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal ]The development of neutralizing antibodies to FIX (FIX inhibitors), as determined by a Bethesda assay. A value of < 0.3 inhibitor units was considered to be no neutralizing antibodies.
- Number of Participants With Cell-Mediated Immune Response to FIX [ Time Frame: 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 ]The development of a cell-mediated immune response to FIX, as determined by enzyme-linked immunospot assay (ELISPOT).
- Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire [ Time Frame: Baseline (Day 0 predose), Weeks 24, 36, 48, End of Study/Early Withdrawal (up to Week 52) ]EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has "no problems" (1), "some problems" (2), or "severe problems" (3).
- Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire [ Time Frame: Baseline (Day 0 predose), Weeks 24, 36, 48, End of Study/Early Withdrawal (up to Week 52) ]The Haemophilia-Specific Quality of Life questionnaire asks subjects about their perceptions of their health and treatment. The questionnaire is divided into the following 10 dimensions: physical health, feelings, view of themselves, sports & leisure, work & school, dealing with hemophilia, treatment, future, family planning, and partnership & sexuality. Questions are based on a 5-point Likert-scale (1=never, 2=rarely, 3=sometimes, 4=often, 5=all the time). If the question does not apply to the subject, the "not applicable" response is allowed in 3 of the domains (sport & leisure, work & school, family planning). Positively worded items need to be re-coded and domains will be transformed ranging from 0 to 100; higher domain and total scores indicating a higher impairment of health-related quality of life.
- Average Weekly Use of FIX Replacement Therapy [ Time Frame: Baseline (Screening), Week 0 through Week 52 ]The use of on-demand FIX replacement therapy was recorded by dose (IU/kg) administered and the average weekly use of FIX replacement therapy was calculated. Participants were not required to stop prophylactic treatment with recombinant FIX until after Week 4 and may have been restarted on their prophylactic recombinant FIX treatment after Week 14.
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
|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|
|Specialized Hospital for Active Treatment for Hematological Disease|
|Sofia, Bulgaria, 1756|
|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|
|Study Director:||Medical Director||Ultragenyx Pharmaceutical Inc|