Hemophilia BPhase 1/2NCT02618915
Safety and Dose Finding Study of DTX101 (AAVrh10FIX) in Adults With Moderate/Severe to Severe Hemophilia B
A Phase 1/2 study testing DTX101 in people with Hemophilia B, run by Ultragenyx Pharmaceutical Inc at 9 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hemophilia B
- What is being tested?
- DTX101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 9 sitesin 3 countries
- Study dates
- 16 Dec 2015to 18 Oct 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
- NOTE: Other protocol defined inclusion/exclusion criteria may apply.
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
United States6 sites
University of Michigan Hospital and Health Systems, Michigan Clinical Research Unit
Ann Arbor, Michigan, 48109
Boston Children's Hospital
Boston, Massachusetts, 02115
University of Florida
Gainesville, Florida, 32610
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Orthopaedic Institute for Children
Los Angeles, California, 90007
Vanderbilt Hemostasis-Thrombosis Clinic
Nashville, Tennessee, 37232
United Kingdom2 sites
Basingstoke and North Hampshire Hospital, Haemophilia, Haemostasis and Thrombosis Centre
Basingstoke, Hampshire, RG24 9NA
The Christie NHS Foundation Trust
Manchester, M20 4BX
Bulgaria1 site
Specialized Hospital for Active Treatment for Hematological Disease
Sofia, 1756
About this study
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
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.
Read the 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
- Being tested
- DTX101
- Keywords
- gene therapy, Hemophilia B
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DTX101Genetic
Also called non-replicating recombinant AAVrh10 encoding human FIX (hFIX), AAVrh10FIX
solution for IV infusion
| Study group | Role | What they receive |
|---|---|---|
| DTX101, Cohort 1 | Experimental | a single peripheral intravenous (IV) infusion of 1.6 x 10^12 genome copies (GC)/kg DTX101 Receives: Genetic: DTX101 |
| DTX101, Cohort 2 | Experimental | a single peripheral IV infusion of 5.0 x 10^12 GC/kg DTX101 Receives: Genetic: DTX101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline, Week 6
Secondary outcomes (8)
Annualized Bleeding Rate
The number of bleeding episodes per participant was recorded, and the annualized number of bleeding episodes was calculated.
Measured: Week 0 to Week 52
Change From Baseline in FIX Activity Over Time
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.
Measured: 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
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.
Measured: Week 0 to Week 52
Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors)
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.
Measured: 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
The development of a cell-mediated immune response to FIX, as determined by enzyme-linked immunospot assay (ELISPOT).
Measured: 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
Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire
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).
Measured: Baseline (Day 0 predose), Weeks 24, 36, 48, End of Study/Early Withdrawal (up to Week 52)
Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire
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.
Measured: Baseline (Day 0 predose), Weeks 24, 36, 48, End of Study/Early Withdrawal (up to Week 52)
Average Weekly Use of FIX Replacement Therapy
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.
Measured: Baseline (Screening), Week 0 through Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2015 (estimated)
- Study start16 Dec 2015
- Primary completion18 Oct 2017
- Study completion18 Oct 2017
Why it stopped: Sponsor decision; not due to any safety concerns related to DTX101.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- More trials run by Ultragenyx Pharmaceutical IncThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02618915
- Sponsor's protocol ID
- 101HEMB01
- Status last verified
- Oct 2018
- First submitted
- 23 Nov 2015
- Last updated
- 14 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40197980
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02618915
- Acronym / sponsor ID
- 101HEMB01
- Conditions
- Hemophilia B
- Keywords
- gene therapy, Hemophilia B
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision; not due to any safety concerns related to DTX101.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- 16 Dec 2015 (actual)
- Primary completion
- 18 Oct 2017 (actual)
- Study completion
- 18 Oct 2017 (actual)
- First posted
- 2 Dec 2015 (estimated)
- Results
- Posted 14 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DTX101, Cohort 1 | Experimental | Genetic: DTX101a single peripheral intravenous (IV) infusion of 1.6 x 10^12 genome copies (GC)/kg DTX101 |
| DTX101, Cohort 2 | Experimental | Genetic: DTX101a single peripheral IV infusion of 5.0 x 10^12 GC/kg DTX101 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DTX101Also: non-replicating recombinant AAVrh10 encoding human FIX (hFIX), AAVrh10FIXsolution for IV infusion | Genetic | DTX101, Cohort 1, DTX101, Cohort 2 |
Primary outcome
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.
8 secondary outcomes
Annualized Bleeding Rate
Time frame: Week 0 to Week 52
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
Annualized FIX Replacement Therapy
Time frame: Week 0 to Week 52
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
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
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)
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)
Average Weekly Use of FIX Replacement Therapy
Time frame: Baseline (Screening), Week 0 through Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40197980Pipe 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Ultragenyx Pharmaceutical Inc
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DTX101 in people with Hemophilia B, run by Ultragenyx Pharmaceutical Inc at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, United Kingdom, Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02618915, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2018.