mRNA-3927 / Moderna - LARVOL DELTA

mRNA-3927-P101: Open-Label Study of mRNA-3927 in Participants With Propionic Acidemia (clinicaltrials.gov) - P1/2 | N=68 | Recruiting | Sponsor: ModernaTX, Inc. | Trial completion date: Jan 2027 ➔ Jan 2026 | Trial primary completion date: Mar 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date

Characterizing the mechanism of action for mRNA therapeutics for the treatment of propionic acidemia, methylmalonic acidemia, and phenylketonuria. (PubMed, Nat Commun) - "These preclinical data were then used to develop translational PK/PD models, which were scaled allometrically to humans to predict starting doses for first-in-human clinical studies for each disease. The predicted first-in-human doses for mRNA-3927, mRNA-3705, and mRNA-3210 were determined to be 0.3, 0.1, and 0.4 mg/kg, respectively."

Journal • Genetic Disorders • Metabolic Disorders • Ophthalmology • Phenylketonuria • Rare Diseases

Interim analyses of a first-in-human phase 1/2 mRNA trial for propionic acidaemia. (PubMed, Nature) - "Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period."

Journal • P1/2 data • Rare Diseases

Open-Label Study of mRNA-3927 in Participants With Propionic Acidemia (clinicaltrials.gov) - P1/2 | N=58 | Recruiting | Sponsor: ModernaTX, Inc. | N=42 ➔ 58

Enrollment change

mRNA-3927 Therapy for Propionic Acidemia: Interim Data from a Phase 1/2 Study (ASGCT 2023) - P1/2 | "To date, mRNA-3927 has been well-tolerated at the doses administered, with encouraging early signs of dose-dependent pharmacology and potential clinical benefit."

P1/2 data • Metabolic Disorders

Translational Pharmacokinetic/Pharmacodynamic Model for mRNA-3927, an Investigational Therapeutic for the Treatment of Propionic Acidemia. (PubMed, Nucleic Acid Ther) - P1/2 | "PCCA/B mRNA PK in mice, rats, and monkeys was adequately described using allometric scaling of volume and clearance parameters. The interspecies preclinical model was scaled allometrically to humans to predict the dose-response relationship in adult and pediatric patients with PA to guide selection of dose range and regimen for the Phase 1 clinical trial (ClinicalTrials.gov Identifier NCT04159103)."

Journal • PK/PD data • Pediatrics

A Long-Term Extension Study to Evaluate the Safety and Clinical Activity of mRNA-3927 (clinicaltrials.gov) - P1/2; N=36; Recruiting; Sponsor: ModernaTX, Inc.

Clinical • New P1/2 trial

Open-Label Study of mRNA-3927 in Participants With Propionic Acidemia (clinicaltrials.gov) - P1/2; N=36; Recruiting; Sponsor: ModernaTX, Inc.; Not yet recruiting ➔ Recruiting; Trial completion date: Jun 2025 ➔ Jan 2027; Trial primary completion date: Jun 2023 ➔ Mar 2025

Clinical • Enrollment open • Trial completion date • Trial primary completion date