A Phase 1/2 Open-Label Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3927 in Participants with Propionic Acidemia

The primary objective is to evaluate the long-term safety of mRNA-3927 in participants with propionic acidemia who were previously enrolled in the mRNA-3927-P101 study. The secondary objective includes:

• Evaluation of the long-term frequency of propionic acidemia-related events.

This clinical trial involves 25 participants diagnosed with propionic acidemia. The study population consists of both male and female patients, including vulnerable individuals. Participants are selected based on their previous involvement in the Study mRNA-3927-P101. Essential requirements for inclusion include the completion of the end-of-treatment or early-termination visit in the prior study. Furthermore, the first dose in the current trial must be administered within 14±3 days following the final dose of mRNA-3927 in the previous study. The participant or a legally authorized representative must be willing to provide informed consent or assent in accordance with local regulations. Compliance with all study-related assessments by the participant and their caregiver is also required.

This Phase 1/2, global, open-label extension study is designed to evaluate the long-term safety and clinical activity of mRNA-3927 in individuals with propionic acidemia. The study includes participants who were previously enrolled in the mRNA-3927-P101 study and completed the end-of-treatment or early termination visit. To maintain continuity, the first dose of the investigational product, a modified messenger ribonucleic acid encoding human propionyl-coenzyme A carboxylase alpha and beta subunits encapsulated into lipid nanoparticles, is planned within 14±3 days of the final dose administered in the preceding study. The primary objective is to monitor the incidence and severity of adverse events, serious adverse events, and events leading to treatment discontinuation. Secondary endpoints include the annualized frequency of investigator-reported metabolic decompensation episodes, hospitalizations, and urgent healthcare encounters related to the condition. The study is estimated to conclude by January 2036.

The experimental medication is mRNA-3927, which consists of modified messenger ribonucleic acid encoding human propionyl-coenzyme A carboxylase alpha and beta subunits encapsulated into lipid nanoparticles. This substance is prepared as a dispersion for injection and is administered via the intravenous route.

The evaluation of clinical activity for Propionic Acidemia involves the assessment of specific secondary endpoints. These include the annualized frequency of metabolic decompensation events (MDEs) and MDE-related hospitalizations as reported by the investigator. Additionally, the study monitors the annualized frequency of PA-related hospitalizations and PA-related urgent healthcare encounters.