Clinical trial NCT05095727: A Study of mRNA-3745 in Adult and Pediatric Participants With Glycogen Storage Disease Type 1a (GSD1a)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-27
Enrollment: 45
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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/exclusion criteria may apply, per protocol.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation
timeFrame: Day 1 up to approximately 3.5 years
Secondary outcomes:
measure: Number of Participants Not Experiencing Hypoglycemia During Fasting Challenges
timeFrame: Baseline through up to Week 32
measure: Change From Baseline of Area Under the Effect Curve (AUEC) of Blood Glucose and Lactate During Fasting Challenges
timeFrame: Baseline through up to Week 32
measure: Change From Baseline in Time to Hypoglycemia During Fasting Challenges
timeFrame: Baseline through up to Week 32
measure: Change From Baseline in Maximum Effect (Emax) During Fasting Challenges
timeFrame: Baseline through up to Week 32
measure: SAD only: Maximum Observed Concentration (Cmax) of Messenger Ribonucleic Acid (mRNA) and Lipid Nanoparticle (LNP)
timeFrame: Pre-infusion, during infusion, at the end of infusion (EOI) and post-infusion on Day 1 up to Week 52
measure: 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
timeFrame: Pre-infusion, during infusion, at EOI and post-infusion on Day 1 up to Week 52
measure: Change From Baseline in Metabolic Biomarkers of GSD1a
timeFrame: Baseline through up to approximately 6.5 years
measure: MAD only: Maximum Observed Concentration at Steady State (Cmax,ss) of mRNA and LNP
timeFrame: Pre-infusion, during infusion, at the EOI and post-infusion on Day 1 up to Week 52
Other outcomes:
Locations:
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Edmonton
country: Canada
facility: Stollery Children's Hospital University of Alberta
state: Alberta
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Clamart
country: France
facility: AP-HP - Hôpital Antoine Béclère
city: Tours
country: France
facility: CHRU Tours - Hopital Clocheville
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Warsaw
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
Study officials:
References:
citation: 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.