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

Phase 3

Active, not recruiting

Conditions: Glycogen Storage Disease Type IA

Interventions: Genetic: DTX401
Other: Placebo
Drug: Oral corticosteroids
Drug: Placebo for oral corticosteroids

Registration Number: NCT05139316

Lead Sponsor: Ultragenyx Pharmaceutical Inc

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.

Detailed 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 & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 49

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
DTX401, Then Placebo	DTX401	Participants receive single peripheral intravenous (IV) infusion of DTX401 in solution. At week 48 participants receive single peripheral IV infusion of Placebo.
DTX401, Then Placebo	Placebo	Participants receive single peripheral intravenous (IV) infusion of DTX401 in solution. At week 48 participants receive single peripheral IV infusion of Placebo.
DTX401, Then Placebo	Oral corticosteroids	Participants receive single peripheral intravenous (IV) infusion of DTX401 in solution. At week 48 participants receive single peripheral IV infusion of Placebo.
DTX401, Then Placebo	Placebo for oral corticosteroids	Participants receive single peripheral intravenous (IV) infusion of DTX401 in solution. At week 48 participants receive single peripheral IV infusion of Placebo.
Placebo, Then DTX401	DTX401	Participants receive single peripheral IV infusion of Placebo. At week 48 eligible participants receive single peripheral IV infusion of DTX401 solution.
Placebo, Then DTX401	Placebo	Participants receive single peripheral IV infusion of Placebo. At week 48 eligible participants receive single peripheral IV infusion of DTX401 solution.
Placebo, Then DTX401	Oral corticosteroids	Participants receive single peripheral IV infusion of Placebo. At week 48 eligible participants receive single peripheral IV infusion of DTX401 solution.
Placebo, Then DTX401	Placebo for oral corticosteroids	Participants receive single peripheral IV infusion of Placebo. At week 48 eligible participants receive single peripheral IV infusion of DTX401 solution.
DTX401 (Japan Only)	DTX401	Participants receive single peripheral intravenous (IV)infusion of DTX401 in solution.
DTX401 (Japan Only)	Oral corticosteroids	Participants receive single peripheral intravenous (IV)infusion of DTX401 in solution.

Primary Outcome Measures

Name	Time	Method
Percent Change from Baseline to Week 48 in Daily Cornstarch Intake	Baseline, Week 48

Secondary Outcome Measures

Name	Time	Method
Patient Global Impression of Change (PGIC) Assessment Score at Week 48	Baseline, Week 48
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
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
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

Trial Locations

Locations (20): Mount Sinai
🇺🇸
Bronx, New York, United States
Osaka City General Hospital
🇯🇵
Osaka, Japan
Kumamoto University Hospital
🇯🇵
Kumamoto, Japan
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
University of Connecticut Health Center
🇺🇸
Farmington, Connecticut, United States
Duke University
🇺🇸
Durham, North Carolina, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
University of Texas
🇺🇸
Houston, Texas, United States
Primary Children's Hospital
🇺🇸
Salt Lake City, Utah, United States
Hospital de Clinicas de Porto Alegre
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
McGill University
🇨🇦
Montréal, Quebec, Canada
Righospitalet
🇩🇰
Kopenhagen, Capital, Denmark
University Medical Center Eppendorf
🇩🇪
Hamburg, Germany
Istituto Giannina Gaslini
🇮🇹
Genova, Linguria, Italy
University of Naples
🇮🇹
Naples, Italy
Fujita Health University Hospital
🇯🇵
Toyoake, Japan
Groningen University
🇳🇱
Groningen, Netherlands
Hospital Clinico Universitario de Santiago
🇪🇸
Santiago De Compostela, A Coruna, Spain