A Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia

NCT04899310 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: mRNA-3705-P1012022-502492-32-00
• Study Type: interventional
• Target: 18
• Locations: 6 countries
• Sites: 11

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

  Up to 134 weeks

• Part 2: Percentage Change in Plasma MMA Levels at Month 3

  Baseline, Month 3

Secondary Outcomes (19)

• Parts 1 and 3: Percentage Change in Plasma MMA Level

  Baseline up to Week 30

• Part 1: Maximum Observed Effect (Emax) for Plasma MMA Measurement after Single and Repeated Administrations of mRNA-3705

  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

  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

  Baseline up to Week 30

• Parts 1-3: Percentage Change in Plasma 2-Methylcitric Acid (2-MC) Levels

  Baseline up to Week 30

Study Arms (2)

mRNA-3705

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

mRNA-3705 BIOLOGICAL

Sterile liquid for infusion

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

mRNA-3705

Placebo BIOLOGICAL

Sterile liquid for infusion

Placebo

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:

• (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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ModernaTX, Inc.: lead

Study Sites (11)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Stollery Children's Hospital University of Alberta

Edmonton, Alberta, T6G 2R7, Canada

Location

Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hôpital Necker - Enfants Malades

Paris, 75015, France

Location

Erasmus MC

Rotterdam, 3015 AA, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hospital Universitario Cruces

Barakaldo, 48903, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Parts 1 and 3 are open label and non-randomized. Part 2 is blinded and randomized.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parts 2 and 3 run in parallel and occur after Part 1.

Study Record Dates

• First Submitted: May 19, 2021
• First Posted: May 24, 2021
• Study Start: August 6, 2021
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

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