GSD1 Clinical Trial
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)
| Verified date | October 2022 |
| Source | Ultragenyx Pharmaceutical Inc |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 12 |
| Est. completion date | November 2, 2021 |
| Est. primary completion date | November 2, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Montreal Children Hospital, McGill University Health Centre | Montréal | Quebec |
| Netherlands | University Medical Center Groningen | Groningen | |
| Spain | Complejo Hospitalario Universitario de Santiago | Santiago De Compostela | A Coruna |
| United States | Michigan Medicine University of Michigan | Ann Arbor | Michigan |
| United States | UCONN Health | Farmington | Connecticut |
| United States | UT Health - McGovern Medical School | Houston | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Ultragenyx Pharmaceutical Inc |
United States, Canada, Netherlands, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events (AEs) Treatment-Emergent AEs (TEAEs) Serious TEAEs, Discontinuations Due to TEAEs, and Dose-Limiting Toxicities (DLTs) | 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. | 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. | |
| Secondary | Change From Baseline in Time to First Hypoglycemic Event Over Time | 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. | Baseline, Weeks 12, 24, 52 |