Recruiting
Phase 1
Phase 2

mRNA-3927

Sponsor:

Moderna

Code:

NCT04159103

Conditions

Propionic Acidemia

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

mRNA-3927

Study Details

Brief summary:

This 3-part, Phase 1/2 study is designed to characterize the safety, tolerability, and pharmacological activity (as assessed by biomarker measurements) and to determine the selected dose of mRNA-3927 in participants with genetically confirmed propionic acidemia (PA). After establishing a dose with an acceptable safety and pharmacodynamic (PD) response for participants ≥1 year of age in Part 1, participants will be enrolled in Part 2 (which will serve as the pivotal study) to allow for determination of the efficacy, safety, and PD of mRNA-3927. Part 3 will evaluate the safety, efficacy and PD response of mRNA-3927 in infants (<1 year of age).

Conditions

Propionic Acidemia

Study ID

NCT04159103

Start date

Apr 15, 2021

Status verified date

Jan, 2026

Completion date

Aug 31, 2027

Anticipated

Primary completion date

Aug 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

77 participants

Anticipated

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1 (Dose Optimization), Part 2 (Pivotal Study), and Part 3 (Infants)

Part 1 (Dose Optimization): Participants (≥1 year of age) will receive single dose of mRNA-3927 by intravenous (IV) infusion every 2 weeks (Q2W) or every 3 weeks (Q3W) for up to 10 doses.

Part 2 (Pivotal Study): Participants (≥1 year of age) will receive single dose of mRNA-3927 (identified during Dose Optimization Phase) by IV infusion Q2W for up to 26 doses or approximately 12 months. Part 3: Participants (<1 year of age) will receive single dose of mRNA-3927 (identified during Dose Optimization Phase) by IV infusion Q2W for up to 26 doses or approximately 12 months.

Interventions

mRNA-3927

mRNA-3927 dispersion for IV infusion

Primary outcome measure

  • Part 1: Number of Participants with Treatment-emergent Adverse Event (TEAE), Serious Adverse Events (SAE) and TEAEs Leading to Discontinuation [ Time Frame: Day 1 (initial mRNA-3927 dose) up to Week 150 (End of Study) ]
  • Part 2: Change in Annualized Frequency of Clinical Event Committee (CEC)-adjudicated Metabolic Decompensation Events (MDEs) During 12-month Treatment Period With mRNA-3927 Compared to Annualized Frequency of CEC-adjudicated MDE During Pretreatment Period [ Time Frame: Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 12 ]
  • Part 3: Number of Participants with TEAEs, SAEs, Adverse Events (AEs) of Special Interest (AESIs) and TEAEs Leading to Discontinuation [ Time Frame: Day 1 up to Week 73 ]

Central Contacts and Locations

Central contacts

Moderna WeCare Team

1-866-663-3762WeCareClinicalTrials@modernatx.com

Locations

Ronald Reagan UCLA Medical Center

Recruiting

Los Angeles, California, United States, 90095

Contacts

Rosemary Silva-Garcia

rsilvagarcia@mednet.ucla.edu

Lucile Packard Children's Hospital Stanford

Recruiting

Stanford, California, United States, 94304

Contacts

650-497-0454hsrobin@stanford.edu

Ann and Robert H Lurie Childrens Hospital of Chicago

Recruiting

Chicago, Illinois, United States, 60611

University of Michigan Hospitals

Recruiting

Ann Arbor, Michigan, United States, 48109

Icahn School of Medicine at Mount Sinai - Clinical Research Unit

Recruiting

New York, New York, United States, 10029

Duke University Medical System (Duke Health)

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Ming Xu

mingfen.xu@duke.edu

Children's Hospital of Philadelphia (CHOP)

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Rebecca Madden

maddenr@chop.edu

Texas Children's Hospital

Recruiting

Houston, Texas, United States, 77030

Contacts

Alyssa Tran

alyssat@bcm.edu

Stollery Children's Hospital University of Alberta

Recruiting

Edmonton, Alberta, Canada, T6G 2R7

Contacts

Cheri Robert

(780) 248-5611cheri.robert@albertahealthservices.ca

Principal Investigator:

Komudi Siriwardena

Hospital For Sick Children

Recruiting

Toronto, Ontario, Canada, M5G 1X8

Contacts

Ashley Wilson

ashley.wilson@sickkids.ca

More Information

Sponsor

ModernaTX, Inc.

Last update posted

Jan 22, 2026

Last verified

Jan, 2026

Keywords

  • mRNA-3927
  • Propionic Aciduria
  • Metabolism, Inborn Errors
  • Genetic Diseases
  • Inborn Amino Acid Metabolism, Inborn Errors
  • Acidosis
  • Acid-Base Imbalance
  • Metabolic Diseases
  • Organic Acidemias
  • Moderna
  • mRNA

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-09. This information was provided to ClinicalTrials.gov by ModernaTX, Inc. on 2026-01-22. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.