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

Glycogen Storage Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05095727
• Other study ID #: mRNA-3745-P102
• Secondary ID: 2022-502963-39-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 1, 2022
• Est. completion date: December 26, 2028

Study information

• Verified date: May 2024
• Source: ModernaTX, Inc.
• Contact: Moderna Clinical Trials Support Center
• Phone: 1-877-777-7187
• Email: clinicaltrials[@]modernatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 26, 2028
• Est. primary completion date: January 7, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• Documented GSD1a with confirmation by genetic testing

• Documented history of a symptomatic hypoglycemic event with blood glucose <60 mg/dL (<3.3 mmol/L)

• 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

• Requirement for continuous feeds via gastrostomy or nasogastric tubes

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

Related Conditions & MeSH terms

• Disease
• Glycogen Storage Disease
• Metabolic Diseases

Intervention

Drug:
• mRNA-3745
Sterile frozen liquid dispersion for injection

Locations

Country	Name	City	State
Canada	Stollery Children's Hospital University of Alberta	Edmonton	Alberta
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Baylor College of Medicine	Houston	Texas
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
ModernaTX, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Change From Baseline of Area Under the Effect Curve (AUEC) of Blood Glucose and Lactate During Fasting Challenges		Baseline through up to Week 32
Secondary	Change From Baseline in Time to Hypoglycemia During Fasting Challenges		Baseline through up to Week 32
Secondary	Change From Baseline in Maximum Effect (Emax) During Fasting Challenges		Baseline through up to Week 32
Secondary	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
Secondary	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
Secondary	Change From Baseline in Metabolic Biomarkers of GSD1a		Baseline through up to approximately 6.5 years
Secondary	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