A Phase 3 Study of Adeno-associated Virus Serotype 8-mediated Gene Transfer of Glucose-6-phosphatase in Patients With Glycogen Storage Disease Type Ia

JRCT ID: jRCT2073230126

Registered date:15/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Glycogen storage disease type Ia
• Date of first enrollment: 31/05/2024
• Target sample size: 4
• Countries of recruitment: United States,Japan,Brazil,Japan,Canada,Japan,Denmark,Japan,Germany,Japan,Italy,Japan,Netherland,Japan,Spain,Japan
• Study type: Interventional

Intervention(s)

Gene Therapy Products: DTX401
On Day1, subjects will receive a single, open-labeled, peripheral IV infusion of DTX401.

Outcome(s)

• Primary Outcome: - To evaluate the efficacy of DTX401 to reduce or eliminate dependence on exogenous glucose replacement therapy needed to maintain glucose control

Secondary Outcome

- To evaluate the effect of DTX401 on reducing the frequency of exogenous glucose replacement therapy
- To evaluate the effect of DTX401 on glucose control
- To evaluate the effect of DTX401 on subject experience of disease
- To evaluate the effect of DTX401 on glucose control
- To evaluate the safety of DTX401

Key inclusion & exclusion criteria

• Age minimum: >= 8age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Male and female patients >= 8 years of age at the time of informed consent or assent.
- Subject has a diagnosis of GSDIa confirmed by deficient enzymatic activity (on liver biopsy), or by molecular testing of G6PC gene revealing 2 pathogenic mutations. In the case where only a single pathogenic mutation is identified, clinical diagnosis is compatible with GSDIa and absence of characteristic features of GSDIb (ie, chronic neutropenia, inflammatory bowel disease).
- Subject is currently receiving a therapeutic regimen of cornstarch (or equivalent), following international guidance/recommendations with stable nutrition, glycemic, and clinical status.

Exclude criteria

- Detectable pre-existing antibodies to the AAV8 capsid during Screening.
- History of liver transplant, including hepatocyte cell therapy/transplant.
- History of severe hepatic fibrosis or cirrhosis as evidenced by any of the following: portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy, or a liver biopsy with evidence of stage III fibrosis.
- Presence of liver adenoma > 5 cm in size or presence of liver adenoma > 3 cm and =< 5 cm in size with a documented annual growth rate of >= 0.5 cm per year.
- Significant hepatic injury or dysfunction as evidenced by imaging or any of the following laboratory abnormalities.
-Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 X the upper limit of normal (ULN)
-Total bilirubin > ULN unless the subject has Gilbert syndrome
-Alkaline phosphatase > ULN, with gamma-glutamyl transferase > ULN
- Non-fasting triglycerides greater than or equal to 1000 mg/dL. For the purposes of this study, non-fasting refers to the longest fasting period that each individual subject is able to tolerate.
- Current or previous participation in another gene transfer study.
Note: Additional inclusion/exclusion criteria may apply, per protocol.

Related Information

• Primary Sponsor: Kajiwara Makoto
• Secondary ID(s): NCT05139316,2020-004184-12