Study Stopped
Study was terminated before the start of dosing due to a business decision and not due to safety or efficacy reasons.
Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia
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
1 other identifier
interventional
N/A
0 countries
N/A
Brief 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.
Trial Health
Trial Health Score
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Started May 2019
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 14, 2019
CompletedFirst Posted
Study publicly available on registry
January 22, 2019
CompletedStudy Start
First participant enrolled
May 28, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 18, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
August 18, 2020
CompletedNovember 13, 2020
November 1, 2020
1.2 years
January 14, 2019
November 10, 2020
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of treatment-emergent adverse events
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
Week -4 through 36 weeks after initial mRNA-3704 dose
Secondary Outcomes (5)
Maximum observed concentration (Cmax) after administration of mRNA-3704
Baseline through 36 weeks after initial mRNA-3704 dose
Time of Cmax (Tmax)
Baseline through 36 weeks after initial mRNA-3704 dose
Area under the plasma concentration-time curve (AUC)
Baseline through 36 weeks after initial mRNA-3704 dose
Change in plasma 2-methylcitrate levels
Week -4 through 36 weeks after initial mRNA-3704 dose
Measurement of anti-PEG antibodies
Pre-dose through up to 52 weeks after final mRNA-3704 dose
Study Arms (5)
Dose Escalation Phase: Dose Level 1
EXPERIMENTALmRNA-3704
Dose Escalation Phase: Dose Level 2
EXPERIMENTALmRNA-3704
Dose Escalation Phase: Dose Level 3
EXPERIMENTALmRNA-3704
Dose Escalation Phase: Dose Level 4 (optional)
EXPERIMENTALmRNA-3704
Dose Expansion Phase: mRNA-3704
EXPERIMENTALInterventions
mRNA-3704 dispersion for intravenous (IV) infusion
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- ModernaTX, Inc.lead
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 14, 2019
First Posted
January 22, 2019
Study Start
May 28, 2019
Primary Completion
August 18, 2020
Study Completion
August 18, 2020
Last Updated
November 13, 2020
Record last verified: 2020-11
Data Sharing
- IPD Sharing
- Will not share