Methylmalonic AcidemiaPhase 1/2NCT05295433
An Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3705 in Participants Previously Enrolled in Other Clinical Studies of mRNA-3705
A Phase 1/2 study testing mRNA-3705 in people with Methylmalonic Acidemia, run by ModernaTX, Inc. at 12 sites in 6 countries.
Trial summary
The primary objective of this study is to evaluate the long-term safety and clinical activity of mRNA-3705 administered to participants with isolated methylmalonic acidemia (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency who have previously participated in other clinical studies of 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?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 12 sitesin 6 countries
- Study dates
- 8 Mar 2022to 2 Apr 2034
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Completed the assigned dose regimen treatment time period in other clinical studies of mRNA-3705 or is eligible for early transition to this study because they missed more than 3 consecutive doses of study drug due to coronavirus disease 2019 (COVID-19) vaccination during Study mRNA-3705-P101 Part 1.
- Completed the End of treatment (EOT) Visit (or End of Study Visit in the case of unscheduled dosing) in Study mRNA-3705-P101 within 10 days of their first dose of mRNA-3705 in this extension study.
Who cannot join
- Not expected to receive clinical benefit from continued mRNA-3705 administration, in the opinion of the Investigator.
- Any clinical or laboratory abnormality or medical condition that, at the discretion of the Investigator, may put the individual at increased risk by participating in this study.
- History of liver and/or kidney transplant.
- NOTE: Other inclusion and exclusion criteria may apply.
Trial locations and contacts
12 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
12 sites in 6 countries
United States3 sites, 3 recruiting
- Recruiting
UCLA Medical Center
Los Angeles, California, 90095
Monserrath Campos, monserrathcampos@mednet.ucla.edu
- Recruiting
Lucile Packard Children's Hospital at Stanford
Palo Alto, California, 94304
Thu Quan, tquan@stanford.edu
- Recruiting
Altman Clinical and Translational Research Institution
San Diego, California, 92037
Nicolle Mendez, n3mendez@health.ucsd.edu
Canada2 sites, 2 recruiting
- Recruiting
Stollery Children's Hospital University of Alberta
Edmonton, Alberta, T6G 2R7
Cheri Copithorne, cheri.robert@ahs.ca
- Recruiting
Hospital For Sick Children
Toronto, Ontario, M5G 1X8
Preet Dhillon, preet.dhillon@sickkids.ca
Netherlands2 sites, 2 recruiting
- Recruiting
Erasmus MC
Rotterdam, 3015 AA
m.wagenmakers@erasmusmc.nl
Margreet Wagenmakers
- Recruiting
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX
s.michel-2@umcutrecht.nl
Sabine Fuchs
Spain2 sites, 2 recruiting
- Recruiting
Hospital Universitario Cruces
Barakaldo, Vizcaya, 48903
Ohiane Martin Rodriguez, ohiane.martinrodriguez@bio-bizkaia.eus
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
Ianire Gallego Amaro, ianireupic@gmail.com
United Kingdom2 sites, 1 recruiting
- Terminated
Birmingham Children's Hospital NHS Foundation Trust
Birmingham, B4 6NH
- Recruiting
Royal Manchester Childrens Hospital
Manchester, M13 9WL
Laura Crowther, genetics.research@mft.nhs.uk
France1 site, 1 recruiting
- Recruiting
Hôpital Necker - Enfants Malades APHP
Paris, 75015
Michaela Semeraro, michaela.semeraro@aphp.fr
About this study
Official title: A Phase 1/2, Global, Open-Label, Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3705 in Participants Previously Enrolled in Other Clinical Studies of mRNA-3705
The primary objective of this study is to evaluate the long-term safety and clinical activity of mRNA-3705 administered to participants with isolated methylmalonic acidemia (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency who have previously participated in other clinical studies of mRNA-3705.
Read the detailed description
Participants with isolated MMA due to MUT deficiency who were previously enrolled in other clinical studies of mRNA-3705 will have the option to enroll into this extension study provided all eligibility criteria have been met. The study will include 2 periods: 1) Treatment Period and 2) Follow-up Period (up to 6 months after the last dose of study drug).
Treatment Period will continue unless one of the following occurs: mRNA-3705 receives marketing approval and reimbursement in the country of origin of the participant (following market approval and access being in place, all participants who wish to continue treatment will be offered mRNA-3705 through market access, with the intention of preventing treatment interruption. Other appropriate access program is offered as allowed by local regulation to continue treatment with mRNA-3705. Safety monitoring will be performed for all participants under treatment per market access requirements), the participant discontinues study drug, the participant is no longer receiving clinical benefit in the opinion of the Investigator, or Sponsor discontinues the development of mRNA-3705.
- Conditions
- Methylmalonic Acidemia
- Being tested
- mRNA-3705
- 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-3705Drug
Also called modified mRNA encoding human, methylmalonyl-coenzyme A mutase
A sterile liquid for injection
| Study group | Role | What they receive |
|---|---|---|
| mRNA-3705 | Experimental | Participants will receive mRNA-3705 at the same dose levels at the same dosing interval (every 2 weeks [Q2W], or every 3 weeks [Q3W]) last received in the clinical study of mRNA-3705 in which they initially participated, unless the Sponsor recommends modification. Receives: Drug: mRNA-3705 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Drug-Related TEAEs, Unrelated TEAEs, Adverse Events of Special Interests (AESIs), Serious Adverse Events (SAEs) and TEAEs Leading to Discontinuation
Measured: Baseline up to follow-up period (up to 6 years + 6 months)
Secondary outcomes (11)
Percent Change in Plasma Methylmalonic Acid and 2-Methylcitric Acid (2-MC) Levels (Primary Biomarkers) From Baseline up to 18 Months
Measured: Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)
Pre- and Postdose Human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA and SM-86 Levels
Measured: Baseline up to 6 years
Change From Baseline in Pretreatment and Post-treatment Annualized Metabolic Decompensation Events (MDEs) Rate
Measured: Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Healthcare Resource Utilization Visits
Measured: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Annualized MMA-related Hospitalizations
Measured: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Annualized MMA-related Healthcare Visits
Measured: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Anti-Polyethylene Glycol (PEG) and Anti-hMUT Antibodies
Measured: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Change in Health-Related Quality of Life (HRQoL) as Measured Using the Pediatric Quality of Life Inventory (PedsQL™) at Month 3 up to 18 Months
Measured: Month 3, Year 6 (Treatment Period) + Month 6 (Follow up)
Change in Investigator Global Assessment of Improvement (IGA-I) Score
Measured: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Change in Investigator Global Assessment of Severity (IGA-S) Score
Measured: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Change in EuroQoL 5-Dimensions 5-level/Youth Questionnaire (EQ-5D-5L/Y) Score
Measured: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2022
- Study start8 Mar 2022
- Primary completion2 Apr 2034 (estimated)
- Study completion2 Apr 2034 (estimated)
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ModernaTX, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05295433
- Sponsor's protocol ID
- mRNA-3705-P101-EXT
- Other IDs
- 2021-000446-17, 2022-501997-20-00
- Status last verified
- Nov 2025
- First submitted
- 14 Feb 2022
- Last updated
- 23 Dec 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Global, Open-Label, Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3705 in Participants Previously Enrolled in Other Clinical Studies of mRNA-3705
- ClinicalTrials.gov ID
- NCT05295433
- Acronym / sponsor ID
- mRNA-3705-P101-EXT
- 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
- Recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- ModernaTX, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Mar 2022 (actual)
- Primary completion
- 2 Apr 2034 (estimated)
- Study completion
- 2 Apr 2034 (estimated)
- First posted
- 25 Mar 2022 (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.
The primary objective of this study is to evaluate the long-term safety and clinical activity of mRNA-3705 administered to participants with isolated methylmalonic acidemia (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency who have previously participated in other clinical studies of mRNA-3705.
Detailed description
Participants with isolated MMA due to MUT deficiency who were previously enrolled in other clinical studies of mRNA-3705 will have the option to enroll into this extension study provided all eligibility criteria have been met. The study will include 2 periods: 1) Treatment Period and 2) Follow-up Period (up to 6 months after the last dose of study drug).
Treatment Period will continue unless one of the following occurs: mRNA-3705 receives marketing approval and reimbursement in the country of origin of the participant (following market approval and access being in place, all participants who wish to continue treatment will be offered mRNA-3705 through market access, with the intention of preventing treatment interruption. Other appropriate access program is offered as allowed by local regulation to continue treatment with mRNA-3705. Safety monitoring will be performed for all participants under treatment per market access requirements), the participant discontinues study drug, the participant is no longer receiving clinical benefit in the opinion of the Investigator, or Sponsor discontinues the development of mRNA-3705.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| mRNA-3705 | Experimental | Drug: mRNA-3705Participants will receive mRNA-3705 at the same dose levels at the same dosing interval (every 2 weeks [Q2W], or every 3 weeks [Q3W]) last received in the clinical study of mRNA-3705 in which they initially participated, unless the Sponsor recommends modification. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Completed the assigned dose regimen treatment time period in other clinical studies of mRNA-3705 or is eligible for early transition to this study because they missed more than 3 consecutive doses of study drug due to coronavirus disease 2019 (COVID-19) vaccination during Study mRNA-3705-P101 Part 1.
- Completed the End of treatment (EOT) Visit (or End of Study Visit in the case of unscheduled dosing) in Study mRNA-3705-P101 within 10 days of their first dose of mRNA-3705 in this extension study.
Key exclusion criteria (4 listed)
- Not expected to receive clinical benefit from continued mRNA-3705 administration, in the opinion of the Investigator.
- Any clinical or laboratory abnormality or medical condition that, at the discretion of the Investigator, may put the individual at increased risk by participating in this study.
- History of liver and/or kidney transplant.
- NOTE: Other inclusion and exclusion criteria may apply.
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 mutaseA sterile liquid for injection | Drug | mRNA-3705 |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Drug-Related TEAEs, Unrelated TEAEs, Adverse Events of Special Interests (AESIs), Serious Adverse Events (SAEs) and TEAEs Leading to Discontinuation
Time frame: Baseline up to follow-up period (up to 6 years + 6 months)
11 secondary outcomes
Percent Change in Plasma Methylmalonic Acid and 2-Methylcitric Acid (2-MC) Levels (Primary Biomarkers) From Baseline up to 18 Months
Time frame: Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)
Pre- and Postdose Human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA and SM-86 Levels
Time frame: Baseline up to 6 years
Change From Baseline in Pretreatment and Post-treatment Annualized Metabolic Decompensation Events (MDEs) Rate
Time frame: Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Healthcare Resource Utilization Visits
Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Annualized MMA-related Hospitalizations
Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Annualized MMA-related Healthcare Visits
Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Number of Anti-Polyethylene Glycol (PEG) and Anti-hMUT Antibodies
Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Change in Health-Related Quality of Life (HRQoL) as Measured Using the Pediatric Quality of Life Inventory (PedsQL™) at Month 3 up to 18 Months
Time frame: Month 3, Year 6 (Treatment Period) + Month 6 (Follow up)
Change in Investigator Global Assessment of Improvement (IGA-I) Score
Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Change in Investigator Global Assessment of Severity (IGA-S) Score
Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Change in EuroQoL 5-Dimensions 5-level/Youth Questionnaire (EQ-5D-5L/Y) Score
Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2025.
- Individual participant dataSharing planned: Undecided
Related trials for Methylmalonic Acidemia
RecruitingObservational study
Clinical and Laboratory Study of Methylmalonic Acidemia
Organic Acidemia, Methylmalonic Acidemia
RecruitingObservational study
A Prospective Study of Pediatric Participants up to 16 Years of Age With Methylmalonic Acidemia (MMA) Due to Mutations in the MMUT Gene
Methylmalonic Acidemia (MMA)
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
Active, not recruitingObservational study
Long-term Follow-up Study of Patients Who Received hLB-001 Gene Therapy
Methylmalonic Acidemia
Not yet recruitingPhase 3
A Study to Evaluate the Effects and Safety of Hydroxocobalamin in Participants With Combined Methylmalonic Academia (cblC Type)
Methylmalonic Acidemia (MMA)
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.
12 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 12 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 2 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 23 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Canada, Netherlands, Spain, United Kingdom 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Moderna WeCare Team (1-866-663-3762, WeCareClinicalTrials@modernatx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Drug-Related TEAEs, Unrelated TEAEs, Adverse Events of Special Interests (AESIs), Serious Adverse Events (SAEs) and TEAEs Leading to Discontinuation (time frame: Baseline up to follow-up period (up to 6 years + 6 months)). 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 23 Dec 2025.