A Study of mRNA-3745 in Participants With Glycogen Storage Disease Type 1a (GSD1a)

Overview

About this study

The purpose of this study is to determine the safety and tolerability of mRNA-3745 and characterize the pharmacokinetics (PK) and pharmacodynamics (PD) response following IV administration of a single dose of mRNA-3745.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- Documented GSD1a with confirmation by genetic testing

- Documented history of ≥1 hypoglycemic event with blood glucose <60
milligrams/deciliter (mg/dL) (<3.3 millimoles/liter [mmol/L]) and symptoms of
hypoglycemia in the absence of acute illness, with at least one such event in the 4
weeks before signing the Informed Consent.

Exclusion Criteria:

- Liver transplant, including hepatocyte cell therapy/transplant

- Received gene therapy for GSD1a

- Presence of liver adenoma >5 centimeters (cm) in size

- Presence of liver adenoma with growth of >2 cm or >5 newly diagnosed liver adenoma, in
the previous 2 years.

Note: Additional inclusion/exclusion criteria may apply, per protocol.

Eligibility last updated 6/8/22. Questions regarding updates should be directed to the study team contact.

More information

Publications

Glycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs). There is no treatment for GSD1a and the current standard-of-care for managing hypoglycemia (Glycosade/modified cornstarch) fails to prevent HCA/HCC risk. Therapeutic modalities such as enzyme replacement therapy and gene therapy are not ideal options for patients due to challenges in drug-delivery, efficacy, and safety. To develop a new treatment for GSD1a capable of addressing both the life-threatening hypoglycemia and HCA/HCC risk, we encapsulated engineered mRNAs encoding human G6Pase-α in lipid nanoparticles. We demonstrate the efficacy and safety of our approach in a preclinical murine model that phenotypically resembles the human condition, thus presenting a potential therapy that could have a significant therapeutic impact on the treatment of GSD1a. Read More on PubMed

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