An Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3705 in Participants Previously Enrolled in Other Clinical Studies of mRNA-3705

NCT05295433 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: mRNA-3705-P101-EXT2021-000446-172022-501997-20-00
• Study Type: interventional
• Target: 56
• Locations: 6 countries
• Sites: 12

Brief Summary

The primary objective of this study is to evaluate the long-term safety and clinical activity of mRNA-3705 administered to participants with isolated methylmalonic acidemia (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency who have previously participated in other clinical studies of mRNA-3705.

Conditions

Methylmalonic Acidemia

Keywords

Isolated Methylmalonic acidemia; Isolated methylmalonic aciduria; Elevated methylmalonic acid (MMA); Metabolism, Inborn Errors; Genetic Diseases; Moderna; mRNA; mRNA-3705

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Drug-Related TEAEs, Unrelated TEAEs, Adverse Events of Special Interests (AESIs), Serious Adverse Events (SAEs) and TEAEs Leading to Discontinuation

  Baseline up to follow-up period (up to 6 years + 6 months)

Secondary Outcomes (11)

• Percent Change in Plasma Methylmalonic Acid and 2-Methylcitric Acid (2-MC) Levels (Primary Biomarkers) From Baseline up to 18 Months

  Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)

• Pre- and Postdose Human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA and SM-86 Levels

  Baseline up to 6 years

• Change From Baseline in Pretreatment and Post-treatment Annualized Metabolic Decompensation Events (MDEs) Rate

  Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)

• Number of Healthcare Resource Utilization Visits

  Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)

• Number of Annualized MMA-related Hospitalizations

  Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)

Study Arms (1)

mRNA-3705

EXPERIMENTAL

Participants will receive mRNA-3705 at the same dose levels at the same dosing interval (every 2 weeks \[Q2W\], or every 3 weeks \[Q3W\]) last received in the clinical study of mRNA-3705 in which they initially participated, unless the Sponsor recommends modification.

Drug: mRNA-3705

Interventions

mRNA-3705 DRUG

A sterile liquid for injection

Also known as: modified mRNA encoding human, methylmalonyl-coenzyme A mutase

mRNA-3705

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Completed the assigned dose regimen treatment time period in other clinical studies of mRNA-3705 or is eligible for early transition to this study because they missed more than 3 consecutive doses of study drug due to coronavirus disease 2019 (COVID-19) vaccination during Study mRNA-3705-P101 Part 1.
• Completed the End of treatment (EOT) Visit (or End of Study Visit in the case of unscheduled dosing) in Study mRNA-3705-P101 within 10 days of their first dose of mRNA-3705 in this extension study.

You may not qualify if:

• Not expected to receive clinical benefit from continued mRNA-3705 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.

Sponsors & Collaborators

• ModernaTX, Inc.: lead

Study Sites (12)

UCLA Medical Center

Los Angeles, California, 90095, United States

RECRUITING

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

RECRUITING

Altman Clinical and Translational Research Institution

San Diego, California, 92037, United States

RECRUITING

Stollery Children's Hospital University of Alberta

Edmonton, Alberta, T6G 2R7, Canada

RECRUITING

Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

Hôpital Necker - Enfants Malades APHP

Paris, 75015, France

RECRUITING

Erasmus MC

Rotterdam, 3015 AA, Netherlands

RECRUITING

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

RECRUITING

Hospital Universitario Cruces

Barakaldo, Vizcaya, 48903, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, B4 6NH, United Kingdom

TERMINATED

Royal Manchester Childrens Hospital

Manchester, M13 9WL, United Kingdom

RECRUITING

MeSH Terms

Conditions

Methylmalonic acidemia; Metabolism, Inborn Errors; Genetic Diseases, Inborn

Interventions

Methylmalonyl-CoA Mutase

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Intramolecular Transferases; Isomerases; Enzymes; Enzymes and Coenzymes

Central Study Contacts

Moderna WeCare Team

CONTACT

1-866-663-3762; WeCareClinicalTrials@modernatx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: March 25, 2022
• Study Start: March 8, 2022
• Primary Completion (Estimated): April 2, 2034
• Study Completion (Estimated): April 2, 2034
• Last Updated: December 23, 2025

Record last verified: 2025-11

Locations

US (3); NL (2); ES (2); GB (2); CA (2); FR (1)