A Study to Assess the Long-term Safety and Clinical Activity of mRNA-3927 in Participants Previously Enrolled in the mRNA-3927-P101 Study

Phase 1

Recruiting

• Conditions: Propionic Acidemia
• Interventions: Biological: mRNA-3927

• Registration Number: NCT05130437
• Lead Sponsor: ModernaTX, Inc.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-11-03
• Study Start: 2021-11-09
• Study First Submitted QC: 2021-11-18
• Study First Posted: 2021-11-23
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-22
• Last Update Posted: 2024-12-27
• Primary Completion: 2029-12-04
• Study Completion: 2031-12-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
mRNA-3927	mRNA-3927	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.

Primary Outcome Measures

Name	Time	Method
Annualized Frequency of Metabolic Decompensation Events (MDEs)	Month 6 through End of Study (up to 8 years)
Number of Participants with Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation	Baseline through End of Study Visit (up to 8 years)

Secondary Outcome Measures

Name	Time	Method
Annualized Frequency of PA-related Hospitalizations	Baseline through End of Study (up to 8 years)
Change From Pretreatment in Pediatric Quality-of-Life Inventory (PedsQL)	Baseline, End of Study (up to 8 years)
Change in 2-Methylcitrate and 3-Hydroxypropionic Acid	Month 3, End of Study (up to 8 years)
Number of Anti-propionyl-CoA Carboxylase (PCC) Antibodies	Month 3 through End of Study (up to 8 years)
Change From Pretreatment in PedsQL Family Impact Module	Baseline, End of Study (up to 8 years)
Change From Pretreatment in Investigator Global Assessment of Improvement (IGA- I)	Baseline, End of Study (up to 8 years)
SM-86 Plasma Concentration After Single and Repeated Dosing	Month 3 through Month 72 (predose, end of infusion)
Annualized Duration of MDEs	Month 6 through End of Study (up to 8 years)
Change From Pretreatment in Methylmalonic Acidemia and Propionic Acidemia Questionnaire-Proximal Signs and Symptoms (MMAPAQ-PSS)	Baseline, End of Study (up to 8 years)
Change From Pretreatment in Investigator Global Assessment of Severity (IGA-S)	Baseline, End of Study (up to 8 years)
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Propionyl-CoA Carboxylase Subunit Alpha (PCCA) mRNA and Propionyl-CoA Carboxylase Subunit Beta (PCCB) mRNA	Month 3 through Month 72 (predose, end of infusion)
PK: Area Under the Curve (AUC) of PCCA mRNA and PCCB mRNA	Month 3 through Month 72 (predose, end of infusion)
Number of Anti-polyethylene Glycol Antibodies	Month 3 through End of Study (up to 8 years)
Change From Pretreatment Prescribed Protein Intake	Baseline, End of Study (up to 8 years)

Trial Locations

Locations (9)

Ronald Reagan UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

Willink Biochemical Genetics Unit - Manchester; 🇬🇧 Manchester, England, United Kingdom

University of Michigan Hospitals; 🇺🇸 Ann Arbor, Michigan, United States

Duke University Medical System (Duke Health); 🇺🇸 Durham, North Carolina, United States

The Children's Hospital of Philadelphia (CHOP); 🇺🇸 Philadelphia, Pennsylvania, United States

Hospital For Sick Children; 🇨🇦 Toronto, Ontario, Canada

University Hospital Birmingham NHS Foundation Trust; 🇬🇧 Birmingham, United Kingdom

Great Ormond Street Hospital for Children NHS Foundation Trust; 🇬🇧 London, United Kingdom