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Sponsor decision; not due to any safety concerns related to DTX101.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DTX101, Cohort 1 | Experimental | a single peripheral intravenous (IV) infusion of 1.6 x 10^12 genome copies (GC)/kg DTX101 |
|
| DTX101, Cohort 2 | Experimental | a single peripheral IV infusion of 5.0 x 10^12 GC/kg DTX101 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DTX101 | Genetic | solution for IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Bleeding Rate | The number of bleeding episodes per participant was recorded, and the annualized number of bleeding episodes was calculated. | Week 0 to Week 52 |
| Change From Baseline in FIX Activity Over Time |
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Inclusion Criteria:
Exclusion Criteria:
NOTE: Other protocol defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Ultragenyx Pharmaceutical Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arkansas Children's Hospital | Little Rock | Arkansas | 72202 | United States | ||
| Orthopaedic Institute for Children |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40197980 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | DTX101, Cohort 1 | a single peripheral intravenous (IV) infusion of 1.6 x 10^12 genome copies (GC)/kg DTX101 |
| FG001 | DTX101, Cohort 2 | a single peripheral IV infusion of 5.0 x 10^12 GC/kg DTX101 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 3, 2015 | Oct 16, 2018 |
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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.
| 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. | 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. | 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). | 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). | 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. | 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. | Baseline (Screening), Week 0 through Week 52 |
| Los Angeles |
| California |
| 90007 |
| United States |
| University of Florida | Gainesville | Florida | 32610 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| University of Michigan Hospital and Health Systems, Michigan Clinical Research Unit | Ann Arbor | Michigan | 48109 | United States |
| Vanderbilt Hemostasis-Thrombosis Clinic | Nashville | Tennessee | 37232 | United States |
| Specialized Hospital for Active Treatment for Hematological Disease | Sofia | 1756 | Bulgaria |
| Basingstoke and North Hampshire Hospital, Haemophilia, Haemostasis and Thrombosis Centre | Basingstoke | Hampshire | RG24 9NA | United Kingdom |
| The Christie NHS Foundation Trust | Manchester | M20 4BX | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | DTX101, Cohort 1 | a single peripheral IV infusion of 1.6 x 10^12 GC/kg DTX101 |
| BG001 | DTX101, Cohort 2 | a single peripheral IV infusion of 5.0 x 10^12 GC/kg DTX101 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number | participants |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||
| Factor IX (FIX) Activity | The documented history or measurement before the Day 0 visit following the appropriate washout was used for the baseline values of FIX activity. | Mean | Standard Deviation | IU/dL |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Safety Set: all participants who received DTX101 including participants who received a partial dose or failed infusion. | Posted | Count of Participants | Participants | up to 52 weeks after dosing (Cohort 1) or 44 weeks after dosing (Cohort 2) |
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| ||||||||||||||||||||||||||||||||||||
| Primary | 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. | As Treated Set: all participants who received any amount of DTX101. | Posted | Mean | Standard Deviation | IU/dL | Baseline, Week 6 |
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| Secondary | Annualized Bleeding Rate | The number of bleeding episodes per participant was recorded, and the annualized number of bleeding episodes was calculated. | As Treated Set: all participants who received any amount of DTX101. | Posted | Mean | Standard Deviation | bleeding episodes/year | Week 0 to Week 52 |
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| Secondary | 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. | As Treated Set: all participants who received any amount of DTX101. | Posted | Mean | Standard Deviation | IU/dL | 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 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | 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. | As Treated Set: all participants who received any amount of DTX101. | Posted | Mean | Standard Deviation | IU/kg | Week 0 to Week 52 |
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| Secondary | 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. | As Treated Set: all participants who received any amount of DTX101. | Posted | Count of Participants | Participants | No | Day 0 (predose), Weeks 6, 8, 16, 32, 40, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | 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). | Safety Set: all participants who received DTX101 including subjects who received a partial dose or failed infusion. | Posted | Count of Participants | Participants | No | 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 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | 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). | Safety Set: all participants who received DTX101 including participants who received a partial dose or failed infusion. | Posted | Count of Participants | Participants | Baseline (Day 0 predose), Weeks 24, 36, 48, End of Study/Early Withdrawal (up to Week 52) |
|
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| Secondary | 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. | Safety Set: all participants who received DTX101 including participants who received a partial dose or failed infusion. | Posted | Count of Participants | Participants | Baseline (Day 0 predose), Weeks 24, 36, 48, End of Study/Early Withdrawal (up to Week 52) |
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| Secondary | 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. | As Treated Set: all participants who received any amount of DTX101, with an assessment at given time point. | Posted | Mean | Standard Deviation | IU/kg | Baseline (Screening), Week 0 through Week 52 |
|
|
From first dose of study drug up to 52 weeks after dosing (Cohort 1) or 44 weeks after dosing (Cohort 2).
TEAEs are presented. 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. Due to concerns related to participant re-identification in this study, events are presented by system organ class only.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DTX101, Cohort 1 | a single peripheral IV infusion of 1.6 x 10^12 GC/kg DTX101 | 0 | 3 | 1 | 3 | 3 | 3 |
| EG001 | DTX101, Cohort 2 | a single peripheral IV infusion of 5.0 x 10^12 GC/kg DTX101 | 0 | 3 | 0 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Investigations | Investigations | MedDRA 18.1 | Systematic Assessment |
| |
| Infections and infestations | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
| |
| Injury, poisoning and procedural complications | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
| |
| Musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
| |
| Gastrointestinal disorders | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
| |
| General disorders and administration site conditions | General disorders | MedDRA 18.1 | Systematic Assessment |
| |
| Nervous system disorders | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
| |
| Respiratory, thoracic and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
| |
| Eye disorders | Eye disorders | MedDRA 18.1 | Systematic Assessment |
| |
| Psychiatric disorders | Psychiatric disorders | MedDRA 18.1 | Systematic Assessment |
| |
| Vascular disorders | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
|
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.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Information | Ultragenyx Pharmaceutical Inc | 1-888-756-8657 | Medinfo@ultragenyx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 6, 2017 | Oct 16, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D002836 | Hemophilia B |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
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| Title | Measurements |
|---|---|
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
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| Units | Counts |
|---|---|
| Participants |
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