Safety and Dose-Finding Study of DTX401 (AAV8G6PC) in Adults With Glycogen Storage Disease Type Ia (GSDIa)

Ultragenyx

Status and phase: Completed; Phase 2; Phase 1

Conditions: GSD1

Treatments: Genetic: DTX401; Drug: steroid regimen

Study type: Interventional

Funder types: Industry

Identifiers

NCT03517085

2016-003023-30 (EudraCT Number)

1706-1617 (Other Identifier)

401GSDIA01

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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12 participants in 4 patient groups

DTX401 Cohort 1

Experimental group

Description:

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)

Treatment:

Genetic: DTX401

Drug: steroid regimen

DTX401 Cohort 2

Experimental group

Description:

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)

Treatment:

Genetic: DTX401

Drug: steroid regimen

DTX401 Cohort 3

Experimental group

Description:

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)

Treatment:

Genetic: DTX401

Drug: steroid regimen

DTX401 Cohort 4

Experimental group

Description:

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)

Treatment:

Genetic: DTX401

Drug: steroid regimen