A Long-Term Extension Study to Evaluate the Safety and Clinical Activity of mRNA-3927

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the long-term safety of mRNA-3927 administered to participants with propionic acidemia (PA) who have previously participated in Study mRNA-3927-P101 (NCT04159103).

Detailed Description
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The study will assess long-term safety and clinical activity of mRNA-3927. Participants with PA who were previously enrolled and completed the end-of-treatment (EOT) Visit of the mRNA-3927-P101 study will have the option to enroll into this extension study provided all eligibility criteria have been met. The study will include 2 periods: 1) Treatment Period and 2) Follow-up Period (up to 2 years after the last dose of study drug). All participants will enter the study receiving mRNA-3927 at the same dose and at the same dosing interval last received in the mRNA-3927-P101 study.

Official Title
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A Phase 1/2, Global, Open-Label, Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3927 in Participants Previously Enrolled in the mRNA-3927-P101 Study

Conditions
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Propionic Acidemia

Intervention / Treatment
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* Biological: mRNA-3927


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participated in Study mRNA-3927-P101. Completed the EOT Visit in Study mRNA-3927-P101 within 10 days of first dose of mRNA-3927 in current study. Exclusion Criteria: Not expected to receive clinical benefit from continued mRNA-3927 administration, in the opinion of the Investigator. Any clinical or laboratory abnormality or medical condition that, at the discretion of the Investigator, may put the individual at increased risk by participating in this study. History of liver and/or kidney transplant.

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-3927<br>Participants will receive the applicable dose identified during Study mRNA-3927-P101 (NCT04159103) on Day 1. The dose can be adjusted based on Sponsor recommendation. | Biological: mRNA-3927<br>* mRNA-3927 dispersion for IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) |  | Baseline up to End of Study Visit (up to 8 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Plasma 2-Methylcitrate (2-MC) Levels |  | Baseline, End of Study (up to 8 years) | 
| Change From Baseline in Plasma 3-Hydroxypropionic Acid (3-HP) Levels |  | Baseline, End of Study (up to 8 years) | 
| Pharmacokinetic (PK): Propionyl-CoA Carboxylase (PCC) Subunit α (PCCA) and Propionyl-CoA Carboxylase Subunit β (PCCB) mRNA (Serum) and SM-86 (Plasma) Levels |  | Predose and End of Infusion up to 8 years postdose | 
| Number of Clinically Significant Events | Clinically significant events include hospitalization, emergency room visits, emergency interventions outside of healthcare settings, and complications of cardiomyopathy treated outside of hospital. | Baseline up to 8 years | 
| Number of Metabolic Decompensation Events (MDEs) |  | Baseline up to 8 years | 
| Number of Healthcare Resource Utilization Visits |  | Baseline up to 8 years | 
| Number of Days Participants Missed School and Workdays |  | Baseline up to 8 years | 
| Number of Anti-Polyethylene Glycol Antibodies |  | Month 6 up to 8 years | 
| Number of Anti-PCC Antibodies |  | Month 6 up to 8 years | 
| Change From Baseline in Pediatric Quality-of-Life Inventory (PedsQL) |  | Baseline, End of Study (up to 8 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-3927, Propionic Aciduria, Metabolism, Inborn Errors, Genetic Diseases, Inborn Amino Acid Metabolism, Inborn Errors, Acidosis, Acid-Base Imbalance, Metabolic Diseases, Organic Acidemias, Moderna, mRNA