Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03810690
• Date of registration: 14/01/2019
• Prospective Registration: Yes
• Primary sponsor: ModernaTX, Inc.
• Public title: Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia
• Scientific 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
• Date of first enrolment: May 28, 2019
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03810690
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Key inclusion & exclusion criteria

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



Age minimum: 1 Year
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Metabolism, Inborn Errors

Methylmalonic Acidemia (MMA)

Intervention(s)

Biological: mRNA-3704

Primary Outcome(s)

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]

Secondary Outcome(s)

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]

Maximum observed concentration (Cmax) after administration of mRNA-3704 [Time Frame: Baseline 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]

Secondary ID(s)

mRNA-3704-P101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors