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

NCT05095727 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: mRNA-3745-P1022022-502963-39-00
• Study Type: interventional
• Target: 15
• Locations: 6 countries
• Sites: 16

Brief Summary

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.

Conditions

Glycogen Storage Disease

Keywords

Glycogen storage disease type 1a; GSD1a; Von Gierke disease; Glucose metabolism disorder; Genetic disorder; Autosomal recessive disorder; messenger RNA; mRNA; Pediatric

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Number of Participants Not Experiencing Hypoglycemia During Fasting Challenges

  Baseline through up to Week 32

• 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

• 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

Study Arms (2)

SAD: mRNA-3745

EXPERIMENTAL

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

MAD: mRNA-3745

EXPERIMENTAL

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

Interventions

mRNA-3745 DRUG

Sterile frozen liquid dispersion for injection

MAD: mRNA-3745; SAD: mRNA-3745

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ModernaTX, Inc.: lead

Study Sites (16)

University of Connecticut Health Center

Farmington, Connecticut, 06030-0001, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Duke University Medical Center

Durham, North Carolina, 27713, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030-1501, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132-0001, United States

Location

Stollery Children's Hospital University of Alberta

Edmonton, Alberta, T6G 2R7, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

AP-HP - Hôpital Antoine Béclère

Clamart, 92140, France

Location

CHRU Tours - Hopital Clocheville

Tours, 37000, France

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, 04-730, Poland

Location

Hospital Universitario 12 de Octubre

Madrid, 28026, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29011, Spain

Location

Related Publications (1)

• 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.

  PMID: 34035281 BACKGROUND

MeSH Terms

Conditions

Glycogen Storage Disease; Glycogen Storage Disease Type I; Glucose Metabolism Disorders; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2021
• First Posted: October 27, 2021
• Study Start: June 1, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

PL (1); US (8); ES (2); FR (2); CA (2); NL (1)