Glycogen Storage Disease
Conditions
Keywords
Glycogen storage disease type 1a, GSD1a, Von Gierke disease, Glucose metabolism disorder, Genetic disorder, Autosomal recessive disorder, messenger RNA, mRNA, Pediatric
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.
Interventions
DRUGmRNA-3745
Sterile frozen liquid dispersion for injection
Sponsors
ModernaTX, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 in Time to Hypoglycemia 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 | — |
| 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 | — |
| Change From Baseline of Area Under the Effect Curve (AUEC) of Blood Glucose and Lactate During Fasting Challenges | Baseline through up to Week 32 | — |
Countries
Canada, France, Netherlands, Poland, Spain, United States
Outcome results
None listed