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

Glycogen Storage Disease Type IA Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05139316
• Other study ID #: DTX401-CL301
• Secondary ID: 2020-004184-12
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 8, 2021
• Est. completion date: February 2026

Study information

• Verified date: March 2024
• Source: Ultragenyx Pharmaceutical Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Study DTX401-CL301 is a phase 3 study to determine the efficacy and confirm the safety of DTX401 in patients 8 years and older with glycogen storage disease type Ia (GSDIa). Participants will be randomized 1:1 to DTX401 or placebo group, and followed closely for 48 weeks. At week 48 eligible participants will cross over and receive DTX401 if they had previously received placebo or placebo if they had previously received DTX401, and will be followed closely for an additional 96 weeks. After completion of week 144 or early withdrawal, participants will be offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post DTX401 infusion. In Japan, there will be a single open label study arm and all participants will be treated with DTX401. At week 48, Japanese participants will be offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post DTX401 infusion.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 46
• Est. completion date: February 2026
• Est. primary completion date: February 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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 Note: additional inclusion/exclusion criteria may apply, per protocol

Related Conditions & MeSH terms

• Disease
• Glycogen Storage Disease
• Glycogen Storage Disease Type I
• Glycogen Storage Disease Type IA
• Metabolic Diseases

Intervention

Genetic:
• DTX401
nonreplicating, recombinant, adeno-associated virus (AAV) serotype 8 (AAV8)

Other:
• Placebo
Normal Saline infusion

Drug:
• Oral corticosteroids
Participants who receive DTX401 solution will receive oral corticosteroids
• Placebo for oral corticosteroids
Participants who receive Placebo will receive placebo oral corticosteroids to maintain the study blind

Locations

Country	Name	City	State
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Canada	McGill University	Montréal	Quebec
Denmark	Righospitalet	Kopenhagen	Capital
Germany	University Medical Center Eppendorf	Hamburg
Italy	Istituto Giannina Gaslini	Genova	Linguria
Italy	University of Naples	Naples
Netherlands	Groningen University	Groningen
Spain	Hospital Clinico Universitario de Santiago	Santiago De Compostela	A Coruna
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Mount Sinai	Bronx	New York
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke University	Durham	North Carolina
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	University of Texas	Houston	Texas
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Primary Children's Hospital	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Ultragenyx Pharmaceutical Inc

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Denmark,  Germany,  Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change from Baseline to Week 48 in Daily Cornstarch Intake		Baseline, Week 48
Secondary	Change from Baseline to Week 48 in Number of Total Daily Doses of Cornstarch in DTX401 Group Compared to Placebo Group		Baseline, Week 48
Secondary	Change from Baseline to Week 48 in Percentage of Glucose Values in Hypoglycemic Range (<70mg/dL [3.9 mmol/L])		Baseline, Week 48
Secondary	Patient Global Impression of Change (PGIC) Assessment Score at Week 48		Baseline, Week 48
Secondary	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
Secondary	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
Secondary	Number of Treatment Emergent Adverse Events (TEAEs), TEAEs of Special Interest, Serious TEAEs, Related TEAEs, Discontinuations From Study or Investigational Product Due to Adverse Events (AEs), and Fatal AEs		up to 144 weeks

External Links

•   Ultragenyx Patient Advocacy/GSDIA Disease Information