Safety and Dose-Finding Study of DTX401 (AAV8G6PC) in Adults With Glycogen Storage Disease Type Ia (GSDIa)
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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: NCT03517085 |
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Recruitment Status :
Completed
First Posted : May 7, 2018
Results First Posted : November 18, 2022
Last Update Posted : November 18, 2022
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Sponsor:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc
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Brief Summary:
The primary objective of the study is to determine the safety of single doses of DTX401, including the incidence of dose-limiting toxicities (DLTs) at each dose level.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| GSD1 | Genetic: DTX401 Drug: steroid regimen | Phase 1 Phase 2 |
Participants enrolled in the 401GSDIA01 study will be monitored for 52 weeks following DTX401 administration. Participants in Cohorts 1, 2, and 3 will receive reactive oral steroid treatment for possible vector-induced hepatitis following treatment with DTX401. Participants in Cohort 4 will receive prophylactic oral steroid treatment to prevent possible vector-induced hepatitis. After completion of the Week 52 visit or early withdrawal, participants will be offered enrollment into a 4-year extension study.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 12 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2, Open-Label Safety and Dose-Finding Study of Adeno-Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Glucose-6- Phosphatase (G6Pase) in Adults With Glycogen Storage Disease Type Ia (GSDIa) |
| Actual Study Start Date : | May 18, 2018 |
| Actual Primary Completion Date : | November 2, 2021 |
| Actual Study Completion Date : | November 2, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Glycogen storage disease type IX
| Arm | Intervention/treatment |
|---|---|
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Experimental: DTX401 Cohort 1
Dose 1 (2.0 × 10^12 GC/kg) with a reactive steroid regimen (6 weeks, at a starting dose of 40 mg/day, after alanine aminotransferase [ALT] elevation)
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Genetic: DTX401
DTX401 administered as a single peripheral intravenous (IV) infusion
Other Names:
Drug: steroid regimen prednisone or prednisolone to manage alanine aminotransferase (ALT) elevation |
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Experimental: DTX401 Cohort 2
Dose 2 (6.0 × 10^12 GC/kg) with a reactive steroid regimen (6 weeks, at a starting dose of 40 mg/day, after ALT elevation)
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Genetic: DTX401
DTX401 administered as a single peripheral intravenous (IV) infusion
Other Names:
Drug: steroid regimen prednisone or prednisolone to manage alanine aminotransferase (ALT) elevation |
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Experimental: DTX401 Cohort 3
Dose 2 (6.0 × 10^12 GC/kg) with an optimized reactive steroid regimen (7 weeks, at a starting dose of 60 mg/day, after ALT elevation)
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Genetic: DTX401
DTX401 administered as a single peripheral intravenous (IV) infusion
Other Names:
Drug: steroid regimen prednisone or prednisolone to manage alanine aminotransferase (ALT) elevation |
|
Experimental: DTX401 Cohort 4
Dose 2 (6.0 × 10^12 GC/kg) with a prophylactic steroid regimen (8 weeks, at a starting dose of 60 mg/day, starting on Day 1)
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Genetic: DTX401
DTX401 administered as a single peripheral intravenous (IV) infusion
Other Names:
Drug: steroid regimen prednisone or prednisolone to manage alanine aminotransferase (ALT) elevation |
Primary Outcome Measures :
- Number of Participants With Adverse Events (AEs) Treatment-Emergent AEs (TEAEs) Serious TEAEs, Discontinuations Due to TEAEs, and Dose-Limiting Toxicities (DLTs) [ Time Frame: AEs Prior to Dosing: From signing the informed consent form (ICF) to first dose of study drug. TEAEs: From first dose of study drug through the End of Study (EOS)/Early Withdrawal visit (up to Week 52) plus 30 days. ]An AE is defined as any untoward medical occurrence, regardless of its causal relationship to study product. An SAE is defined as any event that: results in death; is immediately life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; or an important medical event, in the opinion of the investigator. The relationship to study drug was categorized as unrelated, possible, probable or definite. A DLT is defined as any AE/SAE ≥ Grade 3 that is considered by the Investigator and/or Sponsor to be related to DTX401, based on the Nation Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 or later version. Per protocol, SAEs that occurred > 30 days after EOS or Early withdrawal visit, did not need to be reported unless Investigator considered them related to study product.
Secondary Outcome Measures :
- Change From Baseline in Time to First Hypoglycemic Event Over Time [ Time Frame: Baseline, Weeks 12, 24, 52 ]The change from baseline in time (in hours) to first hypoglycemic event (defined as glucose < 54 mg/dL [< 3.0 mmol/L]) during a controlled fasting challenge at 12, 24, and 52 weeks after IV administration of DTX401. A positive change from baseline is favorable.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Males and females ≥18 years of age
- Documented GSDIa with confirmation by molecular testing
- Documented history of ≥1 hypoglycemic event with blood glucose <60 mg/dL (<3.33 mmol/L)
- Patient's GSDIa disease is stable as evidenced by no hospitalization for severe hypoglycemia during the 4-week period preceding the screening visit
Key Exclusion Criteria:
- Anti-AAV8 neutralizing antibody titer ≥1:5
- Screening or Baseline (Day 0) blood glucose level <60 mg/dL (<3.33 mmol/L)
- Liver transplant, including hepatocyte cell therapy/transplant
- Presence of liver adenoma >5 cm in size
- Presence of liver adenoma >3 cm and ≤5 cm in size that has a documented annual growth rate of ≥0.5 cm per year
- Significant hepatic inflammation or cirrhosis as evidenced by imaging or any of the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limit of normal (ULN), total bilirubin > 1.5 x ULN, or alkaline phosphatase > 2.5 x ULN
Note additional inclusion/exclusion criteria may apply, per protocol.
Information from the National Library of Medicine
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): NCT03517085
Locations
| United States, Connecticut | |
| UCONN Health | |
| Farmington, Connecticut, United States, 06030-3213 | |
| United States, Michigan | |
| Michigan Medicine University of Michigan | |
| Ann Arbor, Michigan, United States, 48109 | |
| United States, Texas | |
| UT Health - McGovern Medical School | |
| Houston, Texas, United States, 77030 | |
| Canada, Quebec | |
| Montreal Children Hospital, McGill University Health Centre | |
| Montréal, Quebec, Canada, H4A3J1 | |
| Netherlands | |
| University Medical Center Groningen | |
| Groningen, Netherlands, 9700RB | |
| Spain | |
| Complejo Hospitalario Universitario de Santiago | |
| Santiago De Compostela, A Coruna, Spain, 15706 | |
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Investigators
| Study Director: | Medical Director | Ultragenyx Pharmaceutical Inc |
Study Documents (Full-Text)
Documents provided by Ultragenyx Pharmaceutical Inc:
Documents provided by Ultragenyx Pharmaceutical Inc:
Study Protocol [PDF] February 16, 2021
Statistical Analysis Plan [PDF] March 4, 2022
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Ultragenyx Pharmaceutical Inc |
| ClinicalTrials.gov Identifier: | NCT03517085 |
| Other Study ID Numbers: |
401GSDIA01 1706-1617 ( Other Identifier: NIH Protocol Registration Number ) 2016-003023-30 ( EudraCT Number ) |
| First Posted: | May 7, 2018 Key Record Dates |
| Results First Posted: | November 18, 2022 |
| Last Update Posted: | November 18, 2022 |
| Last Verified: | October 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Ultragenyx Pharmaceutical Inc:
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glycogen storage disorder Ia AAV gene therapy von Gierke disease glucose metabolism disorder |
Additional relevant MeSH terms:
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Glycogen Storage Disease Carbohydrate Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases |