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Not recruiting
Phase 1
Phase 2

mRNA-3705

Sponsor:

Moderna

Code:

NCT04899310

Conditions

Methylmalonic Acidemia

Eligibility Criteria

Sex: All

Age: 1+

Healthy Volunteers: Not accepted

Interventions

mRNA-3705

Placebo

Study Details

Brief summary:

This is a study of mRNA-3705 in participants with isolated elevated methylmalonic acid (MMA) due to methylmalonyl-coenzyme A (CoA) mutase (MUT) deficiency. The main goal of the study is to assess safety, efficacy, pharmacokinetics, and pharmacodynamics of intravenously (IV)-infused mRNA-3705.

Conditions

Methylmalonic Acidemia

Study ID

NCT04899310

Start date

Aug 6, 2021

Status verified date

Oct, 2025

Completion date

Jul 1, 2028

Anticipated

Primary completion date

Jul 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 1+

Healthy Volunteers: Not accepted

Key Inclusion Criteria:

  • (Part 1 only) Participant has a body weight of ≥11.0 kilograms at the screening visit.
  • Participant has a diagnosis of isolated MMA due to MUT deficiency confirmed by molecular genetic testing.
  • Participant has a blood vitamin B12 level equal to or above the lower limit of normal (based on laboratory reference range) confirmed in the screening period.
  • Participant or their legally authorized representative is willing and able to provide informed consent and/or assent as mandated by local regulations and is willing and able to comply with study-related assessments.
  • Sexually active participants of childbearing or reproductive potential agree to use a highly effective method of contraception, consistent with local regulations, during the study and for 3 months after the last administration of study drug.
  • (Part 2 only) Participants with 2 screening MMA levels ≥400 micromolar.
  • (Parts 2 and 3 only) Participant is ≥5 years of age at the time of informed consent/assent.

Key Exclusion Criteria:

  • Participant has a diagnosis of isolated MMA cofactor adenosyl-cobalamin (cb1A, cb1B, or cb1D) enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria.
  • Participant has previously received gene therapy for the treatment of MMA.
  • Participant has a history of organ transplantation or planned organ transplantation during the period of study participation.
  • Participant has an active, unstable, or clinically significant medical condition not related to MMA or history of noncompliance that, in the investigator's opinion, could potentiate the risk while participating in this study, interfere with the interpretation of study results, or limit the participant's participation in the study. This may include, but is not limited to, history of relevant food or drug allergies; history of cardiovascular, central nervous, gastrointestinal, or infectious disease; history of clinically significant pathology; and/or history of cancer.
  • (Part 2 only) Participant has the partial MUT deficiency disease phenotype, as assessed by genotyping, clinical phenotype/presentation, or vitamin B12-responsive MMA.

Note: Additional inclusion/exclusion criteria may apply, per protocol.

Study Design

Enrollment

74 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: mRNA-3705

Participants in Part 1 will receive a weight-based dose of mRNA-3705, administered IV, once every 2 weeks or once every 3 weeks for up to 10 doses over approximately 40 weeks. Participants in Part 2 and Part 3 will receive mRNA-3705 at the selected dose level and frequency for 3 months.

placebo comparator: Placebo

Participants only in Part 2 will receive placebo at the selected frequency for 3 months.

Interventions

mRNA-3705

Sterile liquid for infusion

Placebo

Sterile liquid for infusion

Primary outcome measure

  • Parts 1 and 3: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Study Drug-related TEAEs, Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation [ Time Frame: Up to 134 weeks ]
  • Part 2: Percentage Change in Plasma MMA Levels at Month 3 [ Time Frame: Baseline, Month 3 ]

Central Contacts and Locations

Central contacts

Moderna WeCare Team

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

Locations

UCLA Medical Center

Recruiting

Los Angeles, California, United States, 90095

Contacts

Campos Monserrath

monserrathcampos@mednet.ucla.edu

Lucile Packard Children's Hospital at Stanford

Recruiting

Palo Alto, California, United States, 94304

Contacts

Thu Quan

tquan@stanford.edu

The Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Rebecca Madden

maddenr@chop.edu

Stollery Children's Hospital University of Alberta

Recruiting

Edmonton, Alberta, Canada, T6G 2R7

Contacts

Cheri Copithorne

cheri.robert@ahs.ca

Hospital For Sick Children

Recruiting

Toronto, Ontario, Canada, M5G 1X8

Contacts

Dhillon Preet

preet.dhillon@sickkids.ca

More Information

Sponsor

ModernaTX, Inc.

Last update posted

Dec 24, 2025

Last verified

Oct, 2025

Keywords

  • Isolated Methylmalonic Acidemia
  • Isolated Methylmalonic Aciduria
  • Elevated Methylmalonic Acid (MMA)
  • Metabolism, Inborn Errors
  • Genetic Diseases
  • Moderna
  • mRNA
  • mRNA-3705

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-23. This information was provided to ClinicalTrials.gov by ModernaTX, Inc. on 2025-12-24.