A Phase 1/2 interventional study of mRNA-3705 and Placebo in Methylmalonic Acidemia, sponsored by ModernaTX, Inc.. Terminated at 11 sites in 6 countries. Open to participants aged 1 Year and older. Per ClinicalTrials.gov, last updated 2026-05-06.
Sponsored by ModernaTX, Inc. (part of Moderna, Inc.) · Phase 1/2, Interventional, and Treatment
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.
This study comprises 3 parts and is designed to evaluate multiple doses and dosing intervals of mRNA-3705.
Parts 1 and 3 are designed to characterize the safety, tolerability, and pharmacological activity of mRNA-3705 administered via intravenous infusion to participants with isolated MMA due to MUT deficiency. Part 2 will evaluate the efficacy of mRNA-3705 as assessed by the change in plasma methylmalonic acid levels.
Participants who complete the treatment period in any part of the study, including the end of treatment (EOT) visit, will be offered participation in the mRNA-extension study (mRNA-3705-P101-EXT; NCT05295433) or may transition to the follow-up period of the study. All participants, including those randomized to placebo in Part 2, will receive mRNA-3705 in the extension study.
26 studies on the registry are indexed under Methylmalonic acidemia; 7 are open to participants now.
This study's enrollment of 18 is below the median of 23 across 12 interventional studies indexed under Methylmalonic acidemia.
Browse Methylmalonic acidemia studies →ModernaTX, Inc. is the lead sponsor of 119 studies on the registry; 18 are open to participants now.
Of its 64 completed or terminated interventional studies of FDA-regulated products, 35 (55%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Additional inclusion/exclusion criteria may apply, per protocol.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Biological: mRNA-3705
Participants only in Part 2 will receive placebo at the selected frequency for 3 months.
Biological: Placebo
Sterile liquid for infusion
Also known as: modified mRNA encoding human, methylmalonyl-coenzyme A mutase
Sterile liquid for infusion
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
Parts 1 and 3: Percentage Change in Plasma MMA Level
Time frame: Baseline up to Week 30
Part 1: Maximum Observed Effect (Emax) for Plasma MMA Measurement after Single and Repeated Administrations of mRNA-3705
Time frame: Baseline up to Week 30
Part 1: Area Below the Baseline and Above the Response Curve (AUC_Below_B) for Plasma MMA Measurement after Single and Repeated Administrations of mRNA-3705
Time frame: Baseline up to Week 30
Part 1: Area Under the Curve that is the Area Under the Response Curve Above the Baseline (AUC_Above_B)-AUC_Below_B (AUC_Net_B) for Plasma MMA Measurement after Single and Repeated Administrations of mRNA-3705
Time frame: Baseline up to Week 30
Parts 1-3: Percentage Change in Plasma 2-Methylcitric Acid (2-MC) Levels
Time frame: Baseline up to Week 30
Parts 1-3: Maximum Observed Concentration (Cmax) of human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA-3705
Time frame: 0 (predose) to 264 hours postdose
Parts 1-3: Area Under the Concentration-Time Curve (AUC) of hMUT mRNA-3705
Time frame: 0 (predose) to 264 hours postdose
Parts 1-3: Titer of Anti-Polyethylene Glycol (PEG) Antibodies
Time frame: 0 (predose) to 336 hours postdose
Parts 2 and 3: Titer of Anti-hMUT Antibodies
Time frame: 0 (predose) to 336 hours postdose
Parts 2 and 3: Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) Physical Function Score
Time frame: Baseline, Month 3
Parts 2 and 3: Annualized Frequency of MMA-related Hospitalizations
Time frame: Baseline up to Month 3
Parts 2 and 3: Annualized Frequency of Metabolic Decompensation Events
Time frame: Baseline up to Month 3
Parts 2 and 3: Change from Baseline in PedsQL Total Score
Time frame: Baseline, Week 47
Parts 2 and 3: Change from Baseline in Investigator Global Assessment of Severity (IGA-S)
Time frame: Baseline, Week 47
Parts 2 and 3: Change from Baseline in Caregiver-Reported Global Impression of Severity (CrGI-S)
Time frame: Baseline, Week 47
Parts 2 and 3: Change from Baseline in Investigator Global Assessment of Improvement (IGA-I)
Time frame: Week 3 (Dose 2), Week 47
Parts 2 and 3: Change from Baseline in Caregiver-Reported Global Impression of Improvement (CrGI-I)
Time frame: Week 3 (Dose 2), Week 47
Part 2: Number of Participants with TEAEs, SAEs, AESIs, and TEAEs Leading to Treatment Discontinuation
Time frame: Up to 47 weeks
Part 2: Plasma Concentration of SM-86
Time frame: 0 (predose) to 48 hours postdose
Ran from Aug 2021 to primary completion in Apr 2026, 55 months.
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This study is terminated, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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