Methylmalonic Acidemia (MMA)Phase 1/2NCT03810690
Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia
A Phase 1/2 study testing mRNA-3704 in people with Methylmalonic Acidemia (MMA) and Metabolism, Inborn Errors, run by ModernaTX, Inc..
Trial summary
This First-in-Human (FIH) Phase 1/2 study will evaluate mRNA-3704 in patients with methylmalonic acidemia/aciduria (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency between 1 to 18 years of age with elevated plasma methylmalonic acid. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Methylmalonic Acidemia (MMA), Metabolism, Inborn Errors
- What is being tested?
- mRNA-3704
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 28 May 2019to 18 Aug 2020
- 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
- Patients are eligible to be included in the study only if all of the following criteria apply:
- Confirmed diagnosis of isolated MMA due to MUT deficiency based on the following criteria:
- Elevated plasma methylmalonic acid concentrations (≥ 100 µmol/L)
- Presence of normal serum/plasma Vitamin B12 and plasma homocysteine levels
- Confirmed diagnosis by molecular genetic testing
- Patient must be ≥ 1 year of age at the time of consent/assent (Inclusion of the first three patients will be restricted to individuals age ≥ 8 years)
Who cannot join
- Patients are excluded from the study if any of the following criteria apply:
- Diagnosis of isolated MMA cblA, cblB, or cblD enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria
- History of organ transplantation
- Previously received gene therapy for the treatment of MMA.
- Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2; or patients who receive chronic dialysis
About this study
Official title: A Global, Phase 1/2, Open Label, Dose Escalation Study to Evaluate the Safety, Pharmacodynamics, and Pharmacokinetics of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency
This First-in-Human (FIH) Phase 1/2 study will evaluate mRNA-3704 in patients with methylmalonic acidemia/aciduria (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency between 1 to 18 years of age with elevated plasma methylmalonic acid. The study is designed to characterize baseline biomarker levels followed by assessment of safety, pharmacokinetics, and pharmacodynamics of different doses of mRNA-3704 in patients affected by MMA as part of the Dose Escalation phase.
During the Dose Escalation phase, three dose levels of mRNA-3704 are planned to be investigated in this study among patients with MMA due to MUT deficiency: low dose, mid dose, and high dose. An additional cohort to evaluate a fourth dose level may be considered jointly by the independent SMC and the Sponsor.
Read more
Upon establishment of a dose with acceptable safety and pharmacodynamic activity, additional patients will be enrolled in a Dose Expansion phase to allow for further characterization of the safety and pharmacodynamics of mRNA-3704.
Patients in both phases of study will participate in a pre-dosing observational period, followed by a treatment period, and then a follow-up period after withdrawal of treatment.
- Being tested
- mRNA-3704
- Medical subject headings
- Methylmalonic acidemia, Metabolism, Inborn Errors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mRNA-3704Biological
mRNA-3704 dispersion for intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Phase: Dose Level 1 | Experimental | mRNA-3704 Receives: Biological: mRNA-3704 |
| Dose Escalation Phase: Dose Level 2 | Experimental | mRNA-3704 Receives: Biological: mRNA-3704 |
| Dose Escalation Phase: Dose Level 3 | Experimental | mRNA-3704 Receives: Biological: mRNA-3704 |
| Dose Escalation Phase: Dose Level 4 (optional) | Experimental | mRNA-3704 Receives: Biological: mRNA-3704 |
| Dose Expansion Phase: mRNA-3704 | Experimental | Not described Receives: Biological: mRNA-3704 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events
Measured: Day 1 (initial mRNA-3704 dose) through 52 weeks after final mRNA-3704 dose
Change in plasma methylmalonic acid levels
Baseline (pre-dose levels) to post-dose levels measured after single and after repeated administrations of mRNA-3704
Measured: Week -4 through 36 weeks after initial mRNA-3704 dose
Secondary outcomes (5)
Maximum observed concentration (Cmax) after administration of mRNA-3704
Measured: Baseline through 36 weeks after initial mRNA-3704 dose
Time of Cmax (Tmax)
Measured: Baseline through 36 weeks after initial mRNA-3704 dose
Area under the plasma concentration-time curve (AUC)
Measured: Baseline through 36 weeks after initial mRNA-3704 dose
Change in plasma 2-methylcitrate levels
Baseline (pre-dose levels) to levels measured after single and after repeated administrations of mRNA-3704
Measured: Week -4 through 36 weeks after initial mRNA-3704 dose
Measurement of anti-PEG antibodies
Measured: Pre-dose through up to 52 weeks after final mRNA-3704 dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2019
- Study start28 May 2019
- Primary completion18 Aug 2020
- Study completion18 Aug 2020
Why it stopped: Study was terminated before the start of dosing due to a business decision and not due to safety or efficacy reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Methylmalonic Acidemia (MMA)Studies 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 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
- NCT03810690
- Sponsor's protocol ID
- mRNA-3704-P101
- Status last verified
- Nov 2020
- First submitted
- 14 Jan 2019
- Last updated
- 13 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Global, Phase 1/2, Open Label, Dose Escalation Study to Evaluate the Safety, Pharmacodynamics, and Pharmacokinetics of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency
- ClinicalTrials.gov ID
- NCT03810690
- Acronym / sponsor ID
- mRNA-3704-P101
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was terminated before the start of dosing due to a business decision and not due to safety or efficacy reasons.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- ModernaTX, Inc.Industry (pharma, biotech, devices)
- Study start
- 28 May 2019 (actual)
- Primary completion
- 18 Aug 2020 (actual)
- Study completion
- 18 Aug 2020 (actual)
- First posted
- 22 Jan 2019 (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 First-in-Human (FIH) Phase 1/2 study will evaluate mRNA-3704 in patients with methylmalonic acidemia/aciduria (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency between 1 to 18 years of age with elevated plasma methylmalonic acid. The study is designed to characterize baseline biomarker levels followed by assessment of safety, pharmacokinetics, and pharmacodynamics of different doses of mRNA-3704 in patients affected by MMA as part of the Dose Escalation phase.
During the Dose Escalation phase, three dose levels of mRNA-3704 are planned to be investigated in this study among patients with MMA due to MUT deficiency: low dose, mid dose, and high dose. An additional cohort to evaluate a fourth dose level may be considered jointly by the independent SMC and the Sponsor.
Upon establishment of a dose with acceptable safety and pharmacodynamic activity, additional patients will be enrolled in a Dose Expansion phase to allow for further characterization of the safety and pharmacodynamics of mRNA-3704.
Patients in both phases of study will participate in a pre-dosing observational period, followed by a treatment period, and then a follow-up period after withdrawal of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Phase: Dose Level 1 | Experimental | Biological: mRNA-3704mRNA-3704 |
| Dose Escalation Phase: Dose Level 2 | Experimental | Biological: mRNA-3704mRNA-3704 |
| Dose Escalation Phase: Dose Level 3 | Experimental | Biological: mRNA-3704mRNA-3704 |
| Dose Escalation Phase: Dose Level 4 (optional) | Experimental | Biological: mRNA-3704mRNA-3704 |
| Dose Expansion Phase: mRNA-3704 | Experimental | Biological: mRNA-3704 |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Patients are eligible to be included in the study only if all of the following criteria apply:
- Confirmed diagnosis of isolated MMA due to MUT deficiency based on the following criteria:
- Patient must be ≥ 1 year of age at the time of consent/assent (Inclusion of the first three patients will be restricted to individuals age ≥ 8 years)
Key exclusion criteria (5 listed)
- Diagnosis of isolated MMA cblA, cblB, or cblD enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria
- History of organ transplantation
- Previously received gene therapy for the treatment of MMA.
- Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2; or patients who receive chronic dialysis
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-3704mRNA-3704 dispersion for intravenous (IV) infusion | Biological | Dose Escalation Phase: Dose Level 1, Dose Escalation Phase: Dose Level 2, Dose Escalation Phase: Dose Level 3, Dose Escalation Phase: Dose Level 4 (optional), Dose Expansion Phase: mRNA-3704 |
Primary outcome
Incidence of treatment-emergent adverse events
Time frame: Day 1 (initial mRNA-3704 dose) through 52 weeks after final mRNA-3704 dose
Change in plasma methylmalonic acid levels
Time frame: Week -4 through 36 weeks after initial mRNA-3704 dose
Baseline (pre-dose levels) to post-dose levels measured after single and after repeated administrations of mRNA-3704
5 secondary outcomes
Maximum observed concentration (Cmax) after administration of mRNA-3704
Time frame: Baseline through 36 weeks after initial mRNA-3704 dose
Time of Cmax (Tmax)
Time frame: Baseline through 36 weeks after initial mRNA-3704 dose
Area under the plasma concentration-time curve (AUC)
Time frame: Baseline through 36 weeks after initial mRNA-3704 dose
Change in plasma 2-methylcitrate levels
Time frame: Week -4 through 36 weeks after initial mRNA-3704 dose
Measurement of anti-PEG antibodies
Time frame: Pre-dose through up to 52 weeks after final mRNA-3704 dose
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2020.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing mRNA-3704 in people with Methylmalonic Acidemia (MMA) and Metabolism, Inborn Errors, run by ModernaTX, Inc..
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 6 inclusion and 5 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: withdrawn, as of the sponsor's last update on 13 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Incidence of treatment-emergent adverse events (time frame: Day 1 (initial mRNA-3704 dose) through 52 weeks after final mRNA-3704 dose). 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 13 Nov 2020.