Home › Trials › NCT04159103

Treatment for Propionic Acidemia using mRNA-3927

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

Phase1; Phase2 Interventional ModernaTX, Inc. · NCT04159103

This study is testing a new treatment called mRNA-3927 to see if it is safe and effective for people with propionic acidemia, including infants and older children.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment77 (estimated)
SexAll
SponsorModernaTX, Inc. Industry-sponsored
Locations35 sites (Los Angeles, California and 34 other locations)
Trial IDNCT04159103 on ClinicalTrials.gov

What this trial studies

This open-label study aims to evaluate the safety, tolerability, and pharmacological activity of mRNA-3927 in participants with genetically confirmed propionic acidemia. The study is divided into three parts: the first part focuses on dose optimization for participants aged one year and older, while the second part expands the participant group to further assess efficacy and safety. The third part specifically evaluates the treatment in infants under one year of age. Participants will undergo a predosing observational period, followed by treatment and a follow-up phase.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged one year and older with a confirmed diagnosis of propionic acidemia, as well as infants identified through newborn screening or with a family history of the condition.

Not a fit: Patients who do not have a confirmed diagnosis of propionic acidemia or those with other metabolic disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of propionic acidemia, potentially leading to better health outcomes for affected patients.

How similar studies have performed: While this approach is novel in the context of propionic acidemia, similar mRNA-based therapies have shown promise in other genetic disorders.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

Participants ≥1 year of age are eligible to be included in the study only if all of the following criteria apply:

* ≥ 8 years of age at the time of consent/assent if enrolled as 1 of the first 2 participants in Part 1.
* ≥1 year of age at the time of consent/assent if enrolled after the first 2 participants in Part 1.
* Confirmed diagnosis of PA based on diagnosis by molecular genetic testing via central laboratory (PCCA and/or PCCB mutations).
* Part 2 only: At least one documented MDE in the 12-month period before consent.

Participants \<1 Year of Age :

* Identification by newborn screening shortly after birth or having suspected PA by presenting with a spectrum of metabolic symptoms, and having a sibling diagnosed with PA. Participant may enter the Screening Period while awaiting genetic testing results, provided that all other eligibility criteria are met but would not be enrolled until diagnosis of PA is confirmed.
* For infants in the neonatal intensive care unit (NICU) only: ≥37 weeks gestational age at the time of birth without other conditions/comorbidities that in the opinion of the Investigator may interfere with the interpretation of study results.
* Body weight ≥3 kilograms (kg) at Screening.
* At least 1 documented PA-related event prior to Screening defined as the following criteria:

  * Clinical signs of metabolic deterioration consistent with PA (for example, vomiting, not feeding well/poor suck, heavy breathing, lethargy, absence of proper perfusion, abnormal movements including bicycling, abnormal tone, low body temperature, seizure\[s\]), OR
  * Meeting the criteria of MDE definition, OR
  * Evidence of laboratory abnormalities as evidenced by at least one of the following:
* Metabolic acidosis with elevated anion gap.
* Acute hyperammonemia.
* Neutropenia or thrombocytopenia.

Exclusion Criteria:

Participants of all ages are excluded from the study if during Screening any of the following criteria apply:

* Any individual with laboratory abnormalities considered to be clinically significant (for example, markedly out of range, associated with clinical symptoms) in the Investigator or Sponsor's opinion that could interfere with or limit the participation in the study.
* Estimated glomerular filtration rate (eGFR) \<30 milliliters (mL)/minute/1.73 square meter (m\^2) for participants of all ages receiving chronic dialysis.
* History of organ transplantation or planned organ transplantation during the period of study participation.
* Corrected QT interval (QTc) \>480 milliseconds (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 Classification.
* Pregnant or breastfeeding.
* Other clinically significant conditions that in the Investigator's opinion could interfere with the safety of the participant, the interpretation of study results, or limit the participation in the study.

Where this trial is running

Los Angeles, California and 34 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Propionic AcidemiamRNA-3927Propionic AciduriaMetabolism, Inborn ErrorsGenetic DiseasesInborn Amino Acid Metabolism, Inborn ErrorsAcidosisAcid-Base Imbalance
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.