Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Other Indications, Other Indications |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 1 - 18 |
| Updated: | 2/6/2019 |
| Start Date: | May 2019 |
| End Date: | November 2024 |
| Contact: | Moderna Clinical Trials |
| Email: | clinicaltrials@modernatx.com |
| Phone: | 855-663-6762 |
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.
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.
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.
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 to ≤ 18 years of age at the time of consent/assent
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
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