A Study to Evaluate mRNA-3745 in Participants with Glycogen Storage Disease Type 1a (GSD1a)

An Open-Label Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of mRNA-3745 in Participants with Glycogen Storage Disease Type 1a (GSD1a)

Objectives: Primary Objectives

• Evaluate the safety and tolerability of messenger RNA encoding human G6Pase-α S298C encapsulated in SM-716, OL-56, Cholesterol, and DSPC (mRNA-3745) via intravenous (IV) administration in participants with glycogen storage disease 1a (GSD1a) Secondary Objectives
• Characterize the pharmacodynamic (PD) response following IV administration of mRNA-3745 assessed by evaluation of blood glucose and lactate levels during fasting challenges
• Characterize the pharmacokinetics (PK) of mRNA encoding human glucose-6-phosphatase-α (hG6PC-α mRNA) and of lipid SM-716, following IV administration of mRNA-3745
• Characterize the PD response to mRNA-3745 as assessed by other GSD1a metabolic biomarkers such as uric acid, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) Exploratory Objectives
• Characterize the change in interstitial glucose trends obtained through a continuous glucose monitoring (CGM) device, following IV administration of mRNA-3745
• Assess for the presence and development of anti-polyethylene glycol (PEG) antibodies and antibodies to the therapeutic protein ie, hG6Pase-α)