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

Metabolism, Inborn Errors Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03810690
• Other study ID #: mRNA-3704-P101
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: May 28, 2019
• Est. completion date: August 18, 2020

Study information

• Verified date: November 2020
• Source: ModernaTX, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 18, 2020
• Est. primary completion date: August 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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

Related Conditions & MeSH terms

• Amino Acid Metabolism, Inborn Errors
• Metabolism, Inborn Errors
• Methylmalonic Acidemia (MMA)

Intervention

Biological:
• mRNA-3704
mRNA-3704 dispersion for intravenous (IV) infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
ModernaTX, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events		Day 1 (initial mRNA-3704 dose) through 52 weeks after final mRNA-3704 dose
Primary	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	Maximum observed concentration (Cmax) after administration of mRNA-3704		Baseline through 36 weeks after initial mRNA-3704 dose
Secondary	Time of Cmax (Tmax)		Baseline through 36 weeks after initial mRNA-3704 dose
Secondary	Area under the plasma concentration-time curve (AUC)		Baseline through 36 weeks after initial mRNA-3704 dose
Secondary	Change in plasma 2-methylcitrate levels	Baseline (pre-dose levels) to levels measured after single and after repeated administrations of mRNA-3704	Week -4 through 36 weeks after initial mRNA-3704 dose
Secondary	Measurement of anti-PEG antibodies		Pre-dose through up to 52 weeks after final mRNA-3704 dose