Open Label Study of mRNA-3927 in Patients With Propionic Acidemia

Brief Title

Open-Label Study of mRNA-3927 in Participants With Propionic Acidemia

Official Title

A Global, Phase 1/2, Open-Label, Dose Optimization Study to Evaluate the Safety, Pharmacodynamics, and Pharmacokinetics of mRNA-3927 in Participants With Propionic Acidemia

Brief Summary

      This First-in-Human (FIH) Phase 1/2 study will evaluate mRNA-3927 in participants 1 year of
      age and older with propionic acidemia (PA). The study is designed to characterize baseline
      biomarker levels followed by assessment of safety, pharmacokinetics (PK), and
      pharmacodynamics (PD) of different doses of mRNA-3927 in participants affected by PA as part
      of the Dose Optimization phase.

Detailed Description

      During the Dose Optimization Stage, after each dose cohort is fully enrolled, and 21 days
      after the final participant in the cohort receives their first dose of study drug, the
      Sponsor will review the totality of available safety data in conjunction with all available
      PK/PD data. Based on this review, the Sponsor will recommend a revised dose and/or dosing
      interval. The Sponsor will abide by predefined constraints as to the maximum percentage
      change in dose and dose interval. A maximum of 5 cohorts will be enrolled into the study.

      Upon establishment of a dose with acceptable safety and pharmacodynamic activity, additional
      participants will be enrolled in a Dose Expansion Stage to allow for further characterization
      of the safety and pharmacodynamics of mRNA-3927.

      Participants in both phases of study will participate in a predosing observational period,
      followed by a treatment period, and then a followup period after withdrawal of treatment.

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

Number of Participants with an Adverse Event (AE)

Secondary Outcome

 Maximum Observed Concentration (Cmax) after Administration of mRNA-3927


Propionic Acidemia



Study Arms / Comparison Groups

 Dose Optimization Stage: Dose Level 1
Description:  Participants will receive 1 dose of Dose Level 1 of mRNA-3927 by intravenous (IV) infusion on Day 1 of a 21-day period for up to 10 doses during the approximate 30-week Treatment Period.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

April 15, 2021

Completion Date

January 6, 2027

Primary Completion Date

March 5, 2025

Eligibility Criteria

        Inclusion Criteria:

          -  Participant must be ≥1 year of age at the time of consent/assent (Inclusion of the
             first 2 participants entering the study at the Dose Escalation stage will be
             restricted to individuals age ≥8 years)

          -  Confirmed diagnosis of propionic acidemia based on diagnosis by molecular genetic
             testing (propionyl-CoA carboxylase subunit α [PCCA] and/or propionyl CoA carboxylase
             subunit β [PCCB] mutations)

        Exclusion Criteria:

          -  Estimated glomerular filtration rate <30 milliliter (mL)/minute/1.73 m^2 as estimated
             by Schwartz formula; or participants who receive chronic dialysis

          -  History of organ transplantation or planned organ transplantation during the period of
             study participation

          -  QTc >480 ms using Bazett's correction

          -  Grade 3 or 4 heart failure according to the Modified Ross Heart Failure Classification
             for Children or the New York Heart Association




1 Year - N/A

Accepts Healthy Volunteers



, 877-913-3286, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

ModernaTX, Inc.

Study Sponsor

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Verification Date

August 2021