A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia (GSDIa)

NCT05139316 | Completed Phase 3 DMC FDA Drug

• 3 other identifiers: DTX401-CL3012020-004184-122023-508750-25-00
• Study Type: interventional
• Target: 49
• Locations: 9 countries
• Sites: 20

Brief Summary

The primary objectives of this study are to evaluate the efficacy of DTX401 to reduce or eliminate dependence on exogenous glucose replacement therapy to maintain euglycemia and to maintain or improve the quality of glucose control.

Conditions

Glycogen Storage Disease Type IA

Keywords

glycogen storage disorder Ia; AAV; gene therapy; von Gierke disease; glucose metabolism disorder; GSDIa; GSD1

Outcome Measures

Primary Outcomes (1)

• Percent Change from Baseline to Week 48 in Daily Cornstarch Intake

  Baseline, Week 48

Secondary Outcomes (6)

• Change from Baseline to Week 48 in Number of Total Daily Doses of Cornstarch in DTX401 Group Compared to Placebo Group

  Baseline, Week 48

• Change from Baseline to Week 48 in Percentage of Glucose Values in Hypoglycemic Range (<70mg/dL [3.9 mmol/L])

  Baseline, Week 48

• Patient Global Impression of Change (PGIC) Assessment Score at Week 48

  Baseline, Week 48

• Change from Baseline to Week 48 in Time to Hypoglycemia (<54 mg/dL [3.0 mmol/L]) During a Controlled Fasting Challenge

  Baseline, Week 48

• Change from Baseline to Week 48 in Percentage of Glucose Values in the Range of 70-120 mg/dL (3.9-6.7 mmol/L)

  Baseline, Week 48

Study Arms (3)

DTX401, Then Placebo

EXPERIMENTAL

Participants receive single peripheral intravenous (IV) infusion of DTX401 in solution. At week 48 participants receive single peripheral IV infusion of Placebo.

Genetic: DTX401; Other: Placebo; Drug: Oral prednisolone; Drug: Placebo for oral prednisolone

Placebo, Then DTX401

PLACEBO COMPARATOR

Participants receive single peripheral IV infusion of Placebo. At week 48 eligible participants receive single peripheral IV infusion of DTX401 solution.

Genetic: DTX401; Other: Placebo; Drug: Oral prednisolone; Drug: Placebo for oral prednisolone

DTX401 (Japan Only)

EXPERIMENTAL

Participants receive single peripheral intravenous (IV)infusion of DTX401 in solution.

Genetic: DTX401; Drug: Oral prednisolone

Interventions

DTX401 GENETIC

nonreplicating, recombinant, adeno-associated virus (AAV) serotype 8 (AAV8)

Also known as: pariglasgene brecaparvovec

DTX401 (Japan Only); DTX401, Then Placebo; Placebo, Then DTX401

Placebo OTHER

Normal Saline infusion

DTX401, Then Placebo; Placebo, Then DTX401

Oral prednisolone DRUG

Participants who receive DTX401 solution will receive oral prednisolone

DTX401 (Japan Only); DTX401, Then Placebo; Placebo, Then DTX401

Placebo for oral prednisolone DRUG

Participants who receive placebo will receive placebo oral prednisolone to maintain the study blind

DTX401, Then Placebo; Placebo, Then DTX401

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented GSDIa with confirmation by molecular testing or enzymatic activity on liver biopsy
• Currently receiving a therapeutic regimen of cornstarch (or equivalent), following international guidance/recommendations with stable nutrition, glycemic, and clinical status.
• Willing and able to complete the informed consent process and to comply with study procedures and visit schedule
• Females of childbearing potential and fertile males must consent to use highly effective contraception from the period following informed consent through the duration of the 144-week study and in cases of early withdrawal at least 48 weeks after the last dose of investigational product (IP). Female subjects must agree not to become pregnant. Male subjects must agree not to father a child or donate sperm

You may not qualify if:

• Detectable pre-existing antibodies to the AAV8 capsid
• History of liver transplant, including hepatocyte cell therapy/ transplant
• History of liver disease
• 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
• Non-fasting triglycerides ≥1000 mg/dL
• Pregnant, breastfeeding, or planning to become pregnant (self or partner) at any time during the study.
• Current or previous participation in another gene transfer study
• History of illicit drug use within 60 days prior to screening or positive results from an 8-panel urine drug screen during the Screening Period completed at 2 time points at least 4 weeks apart

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (20)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Mount Sinai

The Bronx, New York, 10467, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84132, United States

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

McGill University

Montreal, Quebec, H3H 1P3, Canada

Location

Righospitalet

Copenhagen, Capital, 2100, Denmark

Location

University Medical Center Eppendorf

Hamburg, 20251, Germany

Location

Istituto Giannina Gaslini

Genova, Linguria, 16147, Italy

Location

University of Naples

Naples, 80131, Italy

Location

Kumamoto University Hospital

Kumamoto, Japan

Location

Osaka City General Hospital

Osaka, Japan

Location

Fujita Health University Hospital

Toyoake, Japan

Location

Groningen University

Groningen, 9700 RB, Netherlands

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, A Coruna, 15706, Spain

Location

Related Links

• Ultragenyx Patient Advocacy/GSDIA Disease Information
• Ultragenyx Transparency Commitment

MeSH Terms

Conditions

Hepatorenal form of glycogen storage disease; Glycogen Storage Disease Type I; Glucose Metabolism Disorders

Interventions

Prednisolone

Condition Hierarchy (Ancestors)

Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2021
• First Posted: December 1, 2021
• Study Start: November 8, 2021
• Primary Completion: February 20, 2024
• Study Completion: February 20, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); DK (1); DE (1); ES (1); CA (1); JP (3); US (9); BR (1); IT (2)