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

Purpose

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

  • GSD1

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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)
  • Genetic: DTX401
    DTX401 administered as a single peripheral intravenous (IV) infusion
    Other names:
    • AAV8G6PC
    • Pariglasgene brecaparvovec
  • Drug: steroid regimen
    prednisone or prednisolone to manage alanine aminotransferase (ALT) elevation
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)
  • Genetic: DTX401
    DTX401 administered as a single peripheral intravenous (IV) infusion
    Other names:
    • AAV8G6PC
    • Pariglasgene brecaparvovec
  • Drug: steroid regimen
    prednisone or prednisolone to manage alanine aminotransferase (ALT) elevation
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)
  • Genetic: DTX401
    DTX401 administered as a single peripheral intravenous (IV) infusion
    Other names:
    • AAV8G6PC
    • Pariglasgene brecaparvovec
  • 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)
  • Genetic: DTX401
    DTX401 administered as a single peripheral intravenous (IV) infusion
    Other names:
    • AAV8G6PC
    • Pariglasgene brecaparvovec
  • Drug: steroid regimen
    prednisone or prednisolone to manage alanine aminotransferase (ALT) elevation

More Details

Status
Completed
Sponsor
Ultragenyx Pharmaceutical Inc

Study Contact

Detailed 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.