Study of Long-Term Safety and Efficacy on Gene Therapy in Glycogen Storage Disease Type Ia

A Long-Term Follow-up Study to Evaluate the Safety and Efficacy 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)

The primary objective of this study is to determine the long-term safety of DTX401 following a single intravenous (IV) dose in adults with GSDIa.

Study Overview

• Status: Completed
• Conditions: Glycogen Storage Disease Type IA; Von Gierke's Disease (GSD Type Ia)
• Intervention / Treatment: Other: No intervention

Detailed Description

Only participants who received DTX401 in study 401GSDIA01 (NCT03517085) are eligible to participate in study 401GSDIA02. No investigational product will be administered during study 401GSDIA02. Participants will be followed in study 401GSDIA02 for at least 4 years, and up to 6 years after administration of DTX401.

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A3J1
      • Montreal Children Hospital, McGill University Health Centre
• Netherlands
  • Groningen, Netherlands, 9700RB
    • University Medical Center Groningen
• Spain
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago
• United States
  • Connecticut
    • Farmington, Connecticut, United States, 06030-3213
      • UConn Health
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine University of Michigan
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects 18 years of age or older with GSDIa previously enrolled in 401GSDIA01.

Description

Inclusion Criteria:

1. Received DTX401 in study 401GSDIA01.
2. Willing and able to provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures being performed.
3. Willing and able to comply with all scheduled study visits, procedures, and requirements.

Exclusion Criteria:

1. Planned or current participation in any other interventional clinical study that may confound the safety or efficacy evaluation of DTX401 during this study.
2. Presence or history of any condition that, in the view of the Investigator, poses a risk to subject safety or places the subject at high risk of poor compliance or not completing the study or that would significantly affect the interpretation of study results.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DTX401 Cohort 1; Participants received a single intravenous (IV) dose of 2.0 × 10^12 GC/kg DTX401(pariglasgene brecaparvovec) with a reactive steroid regimen during their participation in study 401GSDIA01 (NCT03517085). No intervention was provided during the 401GSDIA02 long term follow up study.	Other: No intervention; No intervention
DTX401 Cohort 2; Participants received a single IV dose of 6.0 × 10^12 GC/kg DTX401(pariglasgene brecaparvovec) with a reactive steroid regimen during their participation in study 401GSDIA01 (NCT03517085). No intervention was provided during the 401GSDIA02 long term follow up study.	Other: No intervention; No intervention
DTX401 Cohort 3; Participants received a single IV dose of 6.0 × 10^12 GC/kg DTX401(pariglasgene brecaparvovec) with an optimized reactive steroid regimen during their participation in study 401GSDIA01 (NCT03517085). No intervention was provided during the 401GSDIA02 long term follow up study.	Other: No intervention; No intervention
DTX401 Cohort 4; Participants received a single IV dose of 6.0 × 10^12 GC/kg DTX401(pariglasgene brecaparvovec) with a prophylactic steroid regimen during their participation in study 401GSDIA01 (NCT03517085). No intervention was provided during the 401GSDIA02 long term follow up study.	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs	An adverse event (AE) is defined as any untoward medical occurrence, regardless of its causal relationship to study product. A TEAE is defined as any AE not present prior to the initiation of the drug treatment or any AE already present that worsens in either intensity or frequency following exposure to the drug treatment. A serious TEAE is an AE that meets any of the following criteria in the view of either the Investigator or Ultragenyx: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; disability/Incapacity; congenital anomaly/birth defect not present at screening; other important medical events. Severity of events were graded as mild (grade 1), moderate (grade 2), severe (grade 3), life-threatening (grade 4), or death (grade 5). As DTX401 was administered as part of Study 401GSDIA01, all AEs in Study 401GSDIA02 were considered TEAEs.	From Baseline (Week 52 of 401GSDIA01/Visit 1 of 401GSDIA02) Up to Week 329

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Time to First Hypoglycemic Event During a Controlled Fasting Challenge 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 the participant's last visit. A positive change from baseline is favorable. Change from baseline is calculated from Baseline (Week 0) of the 401GSDIA01 study.	Baseline (Week 0 of 401GSDIA01), Weeks 52 (Visit 1 of 401GSDIA02), 78, 104, 130, 156, 182, 208, 234, 260, Last Visit (Up to Week 329)

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc
• Investigators: Study Director: Medical Director, Ultragenyx Pharmaceutical Inc

Publications and helpful links

Helpful Links

• Ultragenyx Transparency Commitment

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Actual): February 25, 2025
• Study Completion (Actual): February 25, 2025

Study Registration Dates

• First Submitted: May 29, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 31, 2019

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: gene therapy; genetic diseases; AAV; glucose metabolism disorder; carbohydrate metabolism, inborn errors; Inborn Metabolic Diseases
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Metabolic Diseases; Glycogen Storage Disease; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Genetic Diseases, Inborn; Glucose Metabolism Disorders; Glycogen Storage Disease Type I; Carbohydrate Metabolism, Inborn Errors; Hepatorenal form of glycogen storage disease
• Other Study ID Numbers: 401GSDIA02; 2018-004473-27 (EudraCT Number); 2023-504004-29-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to the rarity of GSDIa and the small number of subjects in this trial, individual patient data will not be shared in order to safeguard patient privacy, consistent with the data sharing commitment statement listed on Ultragenyx.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• product manufactured in and exported from the U.S.: No