Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia (NCT03810690) | Clinical Trial Compass
WithdrawnPhase 1/2
Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia
Stopped: Study was terminated before the start of dosing due to a business decision and not due to safety or efficacy reasons.
0Started 2019-05-28
Plain-language 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. 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.
Who can participate
Age range
1 Year
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
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)
Exclusion Criteria:
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
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Incidence of treatment-emergent adverse events
Timeframe: Day 1 (initial mRNA-3704 dose) through 52 weeks after final mRNA-3704 dose
2
Change in plasma methylmalonic acid levels
Timeframe: Week -4 through 36 weeks after initial mRNA-3704 dose