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

December 22, 2025 updated by: ModernaTX, Inc.

A Phase 1/2, Global, Open-Label, 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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Participants with isolated MMA due to MUT deficiency who were previously enrolled in other clinical studies of mRNA-3705 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 6 months after the last dose of study drug).

Treatment Period will continue unless one of the following occurs: mRNA-3705 receives marketing approval and reimbursement in the country of origin of the participant (following market approval and access being in place, all participants who wish to continue treatment will be offered mRNA-3705 through market access, with the intention of preventing treatment interruption. Other appropriate access program is offered as allowed by local regulation to continue treatment with mRNA-3705. Safety monitoring will be performed for all participants under treatment per market access requirements), the participant discontinues study drug, the participant is no longer receiving clinical benefit in the opinion of the Investigator, or Sponsor discontinues the development of mRNA-3705.

Study Type

Interventional

Enrollment (Estimated)

56

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2R7
        • Recruiting
        • Stollery Children's Hospital University of Alberta
        • Contact:
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
  • France
      • Paris, France, 75015
  • Netherlands
      • Rotterdam, Netherlands, 3015 AA
      • Utrecht, Netherlands, 3584 CX
        • Recruiting
        • Universitair Medisch Centrum Utrecht
        • Contact:
        • Principal Investigator:
          • Sabine Fuchs
  • Spain
  • United Kingdom
      • Birmingham, United Kingdom, B4 6NH
        • Terminated
        • Birmingham Children's Hospital NHS Foundation Trust
      • Manchester, United Kingdom, M13 9WL
  • United States
    • California
      • Los Angeles, California, United States, 90095
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Lucile Packard Children's Hospital at Stanford
        • Contact:
      • San Diego, California, United States, 92037
        • Recruiting
        • Altman Clinical and Translational Research Institution
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

NOTE: Other inclusion and exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: mRNA-3705
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
A sterile liquid for injection
Other Names:
  • modified mRNA encoding human
  • methylmalonyl-coenzyme A mutase

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: Baseline up to follow-up period (up to 6 years + 6 months)
Baseline up to follow-up period (up to 6 years + 6 months)

Secondary Outcome Measures

Outcome Measure
Time Frame
Pre- and Postdose Human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA and SM-86 Levels
Time Frame: Baseline up to 6 years
Baseline up to 6 years
Percent Change in Plasma Methylmalonic Acid and 2-Methylcitric Acid (2-MC) Levels (Primary Biomarkers) From Baseline up to 18 Months
Time Frame: Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)
Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)
Change From Baseline in Pretreatment and Post-treatment Annualized Metabolic Decompensation Events (MDEs) Rate
Time Frame: Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)
Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Healthcare Resource Utilization Visits
Time Frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Annualized MMA-related Hospitalizations
Time Frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Annualized MMA-related Healthcare Visits
Time Frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Anti-Polyethylene Glycol (PEG) and Anti-hMUT Antibodies
Time Frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Change in Health-Related Quality of Life (HRQoL) as Measured Using the Pediatric Quality of Life Inventory (PedsQL™) at Month 3 up to 18 Months
Time Frame: Month 3, Year 6 (Treatment Period) + Month 6 (Follow up)
Month 3, Year 6 (Treatment Period) + Month 6 (Follow up)
Change in Investigator Global Assessment of Improvement (IGA-I) Score
Time Frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Change in Investigator Global Assessment of Severity (IGA-S) Score
Time Frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Change in EuroQoL 5-Dimensions 5-level/Youth Questionnaire (EQ-5D-5L/Y) Score
Time Frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ModernaTX, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 8, 2022

Primary Completion (Estimated)

April 2, 2034

Study Completion (Estimated)

April 2, 2034

Study Registration Dates

First Submitted

February 14, 2022

First Submitted That Met QC Criteria

March 16, 2022

First Posted (Actual)

March 25, 2022

Study Record Updates

Last Update Posted (Estimated)

December 23, 2025

Last Update Submitted That Met QC Criteria

December 22, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • mRNA-3705-P101-EXT
  • 2021-000446-17 (EudraCT Number)
  • 2022-501997-20-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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