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

A Phase 1/2, Adaptive, Open-label, Single Ascending Dose to Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of mRNA-3745 in Participants With Glycogen Storage Disease Type 1a (GSD1a), Followed by an Open-label Extension

The main goal of this trial is to evaluate the safety and tolerability of mRNA-3745 via intravenous (IV) administration in adult and pediatric participants with GSD1a.

Study Overview

• Status: Active, not recruiting
• Conditions: Glycogen Storage Disease
• Intervention / Treatment: Drug: mRNA-3745

Detailed Description

The study includes a single ascending dose (SAD) stage and a multiple ascending dose (MAD) stage. Participants enrolled in the MAD stage have the option to continue treatment in an open-label extension (OLE) period that will assess long-term safety and clinical activity of mRNA-3745.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R7
      • Stollery Children's Hospital University of Alberta
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• France
  • Clamart, France, 92140
    • AP-HP - Hôpital Antoine Béclère
  • Tours, France, 37000
    • CHRU Tours - Hôpital Clocheville
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
• Poland
  • Warsaw, Poland, 04-730
    • Instytut Pomnik Centrum Zdrowia Dziecka
• Spain
  • Madrid, Spain, 28026
    • Hospital Universitario 12 de Octubre
  • Málaga, Spain, 29011
    • Hospital Regional Universitario de Malaga
• United States
  • Connecticut
    • Farmington, Connecticut, United States, 06030-0001
      • University of Connecticut Health Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030-1501
      • The University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132-0001
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented GSD1a with confirmation of biallelic gene encoding glucose-6-phosphatase-α (G6PC) mutations by genetic testing.
• Absence of hospitalization for hypoglycemia in the 4 weeks prior to Screening

Exclusion Criteria:

• Solid organ transplant
• Received gene therapy for GSD1a
• Presence of liver adenoma >5 centimeters (cm) in size
• Diagnosis of type 1 or type 2 diabetes mellitus
• Presence of liver adenoma with growth of >2 cm or >5 newly diagnosed liver adenomas, in the previous 2 years

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAD: mRNA-3745; Participants will receive a single intravenous (IV) dose of mRNA-3745 on Day 1 in an inpatient setting. Participants that are/have been enrolled in the study and receive an administration of mRNA-3745 may also enroll in one of the MAD cohorts. The first MAD dose must occur at least 21 days after the SAD dose.	Drug: mRNA-3745; Sterile frozen liquid dispersion for injection
Experimental: MAD: mRNA-3745; Participants will receive multiple IV doses of mRNA-3745 in an inpatient setting. Participants will have the option to continue treatment in the OLE.	Drug: mRNA-3745; Sterile frozen liquid dispersion for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation	Day 1 up to approximately 3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of Area Under the Effect Curve (AUEC) of Blood Glucose and Lactate During Fasting Challenges		Baseline through up to Week 32
Change From Baseline in Time to Hypoglycemia During Fasting Challenges		Baseline through up to Week 32
Change From Baseline in Maximum Effect (Emax) During Fasting Challenges		Baseline through up to Week 32
Number of Participants Not Experiencing Hypoglycemia During Fasting Challenges	Hypoglycemia is defined as blood glucose <60 milligrams (mg)/deciliter (dL) (3.3 millimoles [mmol]/liter [L]) and/or symptoms of hypoglycemia.	Baseline through up to Week 32
SAD only: Maximum Observed Concentration (Cmax) of Messenger Ribonucleic Acid (mRNA) and Lipid Nanoparticle (LNP)		Pre-infusion, during infusion, at the end of infusion (EOI) and post-infusion on Day 1 up to Week 52
SAD only: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC0-t) of mRNA and LNP		Pre-infusion, during infusion, at EOI and post-infusion on Day 1 up to Week 52
Change From Baseline in Metabolic Biomarkers of GSD1a		Baseline through up to approximately 6.5 years
MAD only: Maximum Observed Concentration at Steady State (Cmax,ss) of mRNA and LNP		Pre-infusion, during infusion, at the EOI and post-infusion on Day 1 up to Week 52

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Publications and helpful links

General Publications

• Cao J, Choi M, Guadagnin E, Soty M, Silva M, Verzieux V, Weisser E, Markel A, Zhuo J, Liang S, Yin L, Frassetto A, Graham AR, Burke K, Ketova T, Mihai C, Zalinger Z, Levy B, Besin G, Wolfrom M, Tran B, Tunkey C, Owen E, Sarkis J, Dousis A, Presnyak V, Pepin C, Zheng W, Ci L, Hard M, Miracco E, Rice L, Nguyen V, Zimmer M, Rajarajacholan U, Finn PF, Mithieux G, Rajas F, Martini PGV, Giangrande PH. mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease. Nat Commun. 2021 May 25;12(1):3090. doi: 10.1038/s41467-021-23318-2.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: October 4, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Estimated): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Pediatric; mRNA; Glycogen storage disease type 1a; GSD1a; Von Gierke disease; Glucose metabolism disorder; Genetic disorder; Autosomal recessive disorder; messenger RNA
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Genetic Diseases, Inborn; Glycogen Storage Disease; Glucose Metabolism Disorders; Glycogen Storage Disease Type I
• Other Study ID Numbers: mRNA-3745-P102; 2022-502963-39-00 (Registry Identifier: Clinical Trials Information System (CTIS))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No