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Assessing mRNA-3705 for treating isolated methylmalonic acidemia

A Global, Phase 1/2, Open-Label, Dose Optimization Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency

Phase1; Phase2 Interventional ModernaTX, Inc. · NCT04899310

This study is testing a new treatment called mRNA-3705 to see if it can help people with isolated methylmalonic acidemia caused by MUT deficiency feel better and improve their health.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment63 (estimated)
Ages1 Year and up
SexAll
SponsorModernaTX, Inc. Industry-sponsored
Locations17 sites (Los Angeles, California and 16 other locations)
Trial IDNCT04899310 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, pharmacokinetics, and pharmacodynamics of mRNA-3705 in participants with isolated methylmalonic acidemia caused by MUT deficiency. It consists of two parts: a Dose Optimization phase to determine the appropriate dosing and a Dose Expansion phase to further assess the treatment's effects. Participants will undergo an Observation Period before receiving treatment and may have the option to join an extension study after completing the treatment. Follow-up assessments will occur over a period of up to two years.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with isolated methylmalonic acidemia due to MUT deficiency, weighing at least 11 kg.

Not a fit: Patients without a confirmed diagnosis of isolated methylmalonic acidemia or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve metabolic control and quality of life for patients with isolated methylmalonic acidemia.

How similar studies have performed: While there have been studies on mRNA therapies for genetic conditions, this specific approach for isolated methylmalonic acidemia is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* Participant has a body weight of ≥11.0 kilograms (kg) 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. For those participants found to have an elevated blood vitamin B12 level, the participant may enter if, in the opinion of the Investigator, the cause of the elevation is secondary to B12 supplementation.
* 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 females of childbearing potential and sexually active males of reproductive potential agree to use a highly-effective method of contraception during the study and for 3 months after the last administration of study drug.
* (Part 2 only) At least 1 documented MDE in the 12-month period before consent.

Key Exclusion Criteria:

* Participant has a diagnosis of isolated MMA 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) History of hepatitis B (known positive hepatitis B surface antigen \[HbsAg\]), hepatitis C virus (HCV), or HIV (positive HIV1/HIV-2 antibodies). Participants with a past or resolved hepatitis virus B (HBV) infection (defined as the presence of hepatitis B core antibody and absence of HbsAg) are eligible. Participants with history of positive results for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

Where this trial is running

Los Angeles, California and 16 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Methylmalonic AcidemiaIsolated Methylmalonic acidemiaIsolated methylmalonic aciduriaelevated methylmalonic acidMetabolism, Inborn ErrorsGenetic DiseasesModernamRNA
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.