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

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

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.

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.

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