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

Phase 1

Recruiting

• Conditions: Glycogen Storage Disease
• Interventions: Drug: mRNA-3745

• Registration Number: NCT05095727
• Lead Sponsor: ModernaTX, Inc.

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.

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 Timeline

• Study First Submitted: 2021-10-04
• Study First Submitted QC: 2021-10-14
• Study First Posted: 2021-10-27
• Study Start: 2022-06-01
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-24
• Last Update Posted: 2024-10-28
• Primary Completion: 2026-05-26
• Study Completion: 2028-12-26

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
SAD: mRNA-3745	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.
MAD: mRNA-3745	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Number of Participants Not Experiencing Hypoglycemia During Fasting Challenges	Baseline through up to Week 32	Hypoglycemia is defined as blood glucose \<60 milligrams (mg)/deciliter (dL) (3.3 millimoles \[mmol\]/liter \[L\]) and/or symptoms of hypoglycemia.
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
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
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
Change From Baseline in Maximum Effect (Emax) During Fasting Challenges	Baseline through up to Week 32
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

Trial Locations

Locations (10)

University of Connecticut Health Center; 🇺🇸 Farmington, Connecticut, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Hospital Regional Universitario de Malaga; 🇪🇸 Malaga, Spain

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

Stollery Children's Hospital University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States