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

Sponsor

Ultragenyx Pharmaceutical Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT03517085

Collaborator

(none)

Enrollment

Locations

Arms

39.3

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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	Phase 1/Phase 2

Detailed Description

Subjects enrolled in the 401GSDIA01 study will be monitored for 52 weeks following DTX401 administration. Subjects in Cohorts 1, 2, and 3 will receive reactive oral steroid treatment for possible vector-induced hepatitis following treatment with DTX401. Subjects 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, subjects will be offered enrollment into a 4-year extension study.

Study Design

Study Type:

Interventional

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 :

Jul 24, 2018

Actual Primary Completion Date :

Nov 2, 2021

Actual Study Completion Date :

Nov 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DTX401 Dose 1 DTX401 solution for intravenous (IV) infusion	Genetic: DTX401 DTX401 administered as a single peripheral IV infusion Other Names: AAV8G6PC
Experimental: DTX401 Dose 2 DTX401 solution for intravenous (IV) infusion	Genetic: DTX401 DTX401 administered as a single peripheral IV infusion Other Names: AAV8G6PC
Experimental: DTX401 Dose 3 DTX401 solution for intravenous (IV) infusion	Genetic: DTX401 DTX401 administered as a single peripheral IV infusion Other Names: AAV8G6PC
Experimental: DTX401 Dose 4 DTX401 solution for intravenous (IV) infusion	Genetic: DTX401 DTX401 administered as a single peripheral IV infusion Other Names: AAV8G6PC

Outcome Measures

Primary Outcome Measures

Adverse Events (AEs), Treatment-emergent Adverse Events (TEAEs), and Serious Adverse Events (SAEs) [Up to 52 Weeks]

Secondary Outcome Measures

Change from Baseline in Time (Minutes) to First Hypoglycemic Event During a Controlled Fasting Challenge at Weeks 12, 24, and 52 [Baseline and Weeks 12, 24, and 52]
The change from baseline in time (in minutes) to first hypoglycemic event (defined as glucose <54 mg/dL [<3.0 mmol/L]) during a controlled fasting challenge after IV administration of DTX401).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 × ULN, alkaline phosphatase >2.5 × ULN

Note additional inclusion/exclusion criteria may apply, per protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCONN Health	Farmington	Connecticut	United States	06030-3213
2	Michigan Medicine University of Michigan	Ann Arbor	Michigan	United States	48109
3	UT Health - McGovern Medical School	Houston	Texas	United States	77030
4	Montreal Children Hospital, McGill University Health Centre	Montréal	Quebec	Canada	H4A3J1
5	University Medical Center Groningen	Groningen		Netherlands	9700RB
6	Complejo Hospitalario Universitario de Santiago	Santiago De Compostela	A Coruna	Spain	15706