A Study of mRNA-3745 in Adult and Pediatric Participants With Glycogen Storage Disease Type 1a (GSD1a)
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 45
- Documented GSD1a with confirmation of biallelic gene encoding glucose-6-phosphatase-ฮฑ (G6PC) mutations by genetic testing.
- Absence of hospitalization for hypoglycemia in the 4 weeks prior to Screening
- 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 & 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 (16)
Hospital Universitario 12 de Octubre
๐ช๐ธMadrid, Spain
Hospital Regional Universitario de Malaga
๐ช๐ธMalaga, Spain
The Hospital for Sick Children
๐จ๐ฆToronto, Ontario, Canada
Universitair Medisch Centrum Groningen
๐ณ๐ฑGroningen, Netherlands
University of Connecticut Health Center
๐บ๐ธFarmington, Connecticut, United States
Boston Children's Hospital
๐บ๐ธBoston, Massachusetts, United States
Duke University Medical Center
๐บ๐ธDurham, North Carolina, United States
The University of Texas Health Science Center at Houston
๐บ๐ธHouston, Texas, United States
CHRU Tours - Hopital Clocheville
๐ซ๐ทTours, France
Cincinnati Children's Hospital Medical Center
๐บ๐ธCincinnati, Ohio, United States
Children's Hospital of Philadelphia
๐บ๐ธPhiladelphia, Pennsylvania, United States
Baylor College of Medicine
๐บ๐ธHouston, Texas, United States
AP-HP - Hรดpital Antoine Bรฉclรจre
๐ซ๐ทClamart, France
Instytut Pomnik Centrum Zdrowia Dziecka
๐ต๐ฑWarsaw, Poland
University of Utah
๐บ๐ธSalt Lake City, Utah, United States
Stollery Children's Hospital University of Alberta
๐จ๐ฆEdmonton, Alberta, Canada