Methylmalonic AcidemiaPhase 1/2NCT04899310
A Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia
A Phase 1/2 study testing mRNA-3705 in people with Methylmalonic Acidemia, run by ModernaTX, Inc. at 11 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Methylmalonic Acidemia
- What is being tested?
- mRNA-3705
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 11 sitesin 6 countries
- Study dates
- 6 Aug 2021to 1 Apr 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- (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.
Who cannot join
- 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.
Trial locations and contacts
11 sites in 6 countries.
11 sites in 6 countries
United States3 sites
UCLA Medical Center
Los Angeles, California, 90095
Lucile Packard Children's Hospital at Stanford
Palo Alto, California, 94304
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Canada2 sites
Stollery Children's Hospital University of Alberta
Edmonton, Alberta, T6G 2R7
Hospital For Sick Children
Toronto, Ontario, M5G 1X8
Netherlands2 sites
Erasmus MC
Rotterdam, 3015 AA
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX
Spain2 sites
Hospital Universitario Cruces
Barakaldo, 48903
Hospital Universitario 12 de Octubre
Madrid, 28041
United Kingdom1 site
Royal Manchester Children's Hospital
Manchester, M13 9WL
About this study
Official title: A Global Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency
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.
Read the detailed description
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.
- Conditions
- Methylmalonic Acidemia
- Being tested
- mRNA-3705, Placebo
- Keywords
- Isolated Methylmalonic Acidemia, Isolated Methylmalonic Aciduria, Elevated Methylmalonic Acid (MMA), Metabolism, Inborn Errors, Genetic Diseases, Moderna, mRNA, mRNA-3705
- Medical subject headings
- Methylmalonic acidemia, Metabolism, Inborn Errors, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mRNA-3705Biological
Also called modified mRNA encoding human, methylmalonyl-coenzyme A mutase
Sterile liquid for infusion
PlaceboBiological
Sterile liquid for infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: mRNA-3705 |
| Placebo | Placebo comparator | Participants only in Part 2 will receive placebo at the selected frequency for 3 months. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 134 weeks
Part 2: Percentage Change in Plasma MMA Levels at Month 3
Measured: Baseline, Month 3
Secondary outcomes (19)
Parts 1 and 3: Percentage Change in Plasma MMA Level
Measured: Baseline up to Week 30
Part 1: Maximum Observed Effect (Emax) for Plasma MMA Measurement after Single and Repeated Administrations of mRNA-3705
Measured: 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
Measured: 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
Measured: Baseline up to Week 30
Parts 1-3: Percentage Change in Plasma 2-Methylcitric Acid (2-MC) Levels
Measured: Baseline up to Week 30
Parts 1-3: Maximum Observed Concentration (Cmax) of human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA-3705
Measured: 0 (predose) to 264 hours postdose
Parts 1-3: Area Under the Concentration-Time Curve (AUC) of hMUT mRNA-3705
Measured: 0 (predose) to 264 hours postdose
Parts 1-3: Titer of Anti-Polyethylene Glycol (PEG) Antibodies
Measured: 0 (predose) to 336 hours postdose
Parts 2 and 3: Titer of Anti-hMUT Antibodies
Measured: 0 (predose) to 336 hours postdose
Parts 2 and 3: Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) Physical Function Score
Measured: Baseline, Month 3
Parts 2 and 3: Annualized Frequency of MMA-related Hospitalizations
Measured: Baseline up to Month 3
Parts 2 and 3: Annualized Frequency of Metabolic Decompensation Events
Measured: Baseline up to Month 3
Parts 2 and 3: Change from Baseline in PedsQL Total Score
Measured: Baseline, Week 47
Parts 2 and 3: Change from Baseline in Investigator Global Assessment of Severity (IGA-S)
Measured: Baseline, Week 47
Parts 2 and 3: Change from Baseline in Caregiver-Reported Global Impression of Severity (CrGI-S)
Measured: Baseline, Week 47
Parts 2 and 3: Change from Baseline in Investigator Global Assessment of Improvement (IGA-I)
Measured: Week 3 (Dose 2), Week 47
Parts 2 and 3: Change from Baseline in Caregiver-Reported Global Impression of Improvement (CrGI-I)
Measured: Week 3 (Dose 2), Week 47
Part 2: Number of Participants with TEAEs, SAEs, AESIs, and TEAEs Leading to Treatment Discontinuation
Measured: Up to 47 weeks
Part 2: Plasma Concentration of SM-86
Measured: 0 (predose) to 48 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2021
- Study start6 Aug 2021
- Primary completion1 Apr 2026
- Study completion1 Apr 2026
Why it stopped: As part of ongoing efforts to refine the MMA program strategy, we are reevaluating clinical study plans for mRNA-3705, in order to further optimize the development program. As part of this process, Moderna will be closing the mRNA-3705-P101 study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Methylmalonic AcidemiaStudies of the same condition, open and under way.
- More trials run by ModernaTX, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parts 2 and 3 run in parallel and occur after Part 1.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- ModernaTX, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04899310
- Sponsor's protocol ID
- mRNA-3705-P101
- Other IDs
- 2022-502492-32-00
- Status last verified
- Apr 2026
- First submitted
- 19 May 2021
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Global Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency
- ClinicalTrials.gov ID
- NCT04899310
- Acronym / sponsor ID
- mRNA-3705-P101
- Conditions
- Methylmalonic Acidemia
- Keywords
- Isolated Methylmalonic Acidemia, Isolated Methylmalonic Aciduria, Elevated Methylmalonic Acid (MMA), Metabolism, Inborn Errors, Genetic Diseases, Moderna, mRNA, mRNA-3705
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: As part of ongoing efforts to refine the MMA program strategy, we are reevaluating clinical study plans for mRNA-3705, in order to further optimize the development program. As part of this process, Moderna will be closing the mRNA-3705-P101 study.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- ModernaTX, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Aug 2021 (actual)
- Primary completion
- 1 Apr 2026 (actual)
- Study completion
- 1 Apr 2026 (actual)
- First posted
- 24 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parts 2 and 3 run in parallel and occur after Part 1.
| Arm | Type | Receives |
|---|---|---|
| mRNA-3705 | Experimental | Biological: mRNA-3705Participants 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 | Placebo comparator | Biological: PlaceboParticipants only in Part 2 will receive placebo at the selected frequency for 3 months. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- (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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mRNA-3705Also: modified mRNA encoding human, methylmalonyl-coenzyme A mutaseSterile liquid for infusion | Biological | mRNA-3705 |
| PlaceboSterile liquid for infusion | Biological | Placebo |
Primary outcome
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
19 secondary outcomes
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
Results and safety
The study was stopped early (reason given: As part of ongoing efforts to refine the MMA program strategy, we are reevaluating clinical study plans for mRNA-3705, in order to further optimize the development program. As part of this process, Moderna will be closing the mRNA-3705-P101 study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing mRNA-3705 in people with Methylmalonic Acidemia, run by ModernaTX, Inc. at 11 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada, Netherlands, Spain, France and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: As part of ongoing efforts to refine the MMA program strategy, we are reevaluating clinical study plans for mRNA-3705, in order to further optimize the development program. As part of this process, Moderna will be closing the mRNA-3705-P101 study.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.