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

Last updated: October 29, 2025
Sponsor: ModernaTX, Inc.
Overall Status: Active - Recruiting

Phase

1/2

Condition

Distal Renal Tubular Acidosis

Phenylketonuria

Metabolic Disorders

Treatment

mRNA-3927

Clinical Study ID

NCT04159103
mRNA-3927-P101
2022-502910-10
2022-502910-10-00
  • All Genders

Study 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).

Eligibility Criteria

Inclusion

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 2participants in Part 1.

  • ≥1 year of age at the time of consent/assent if enrolled after the first 2participants in Part 1.

  • Confirmed diagnosis of PA based on diagnosis by molecular genetic testing viacentral 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 bypresenting with a spectrum of metabolic symptoms, and having a sibling diagnosedwith PA. Participant may enter the Screening Period while awaiting genetic testingresults, provided that all other eligibility criteria are met but would not beenrolled until diagnosis of PA is confirmed.

  • For infants in the neonatal intensive care unit (NICU) only: ≥37 weeks gestationalage at the time of birth without other conditions/comorbidities that in the opinionof 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 followingcriteria:

  • Clinical signs of metabolic deterioration consistent with PA (for example,vomiting, not feeding well/poor suck, heavy breathing, lethargy, absence ofproper perfusion, abnormal movements including bicycling, abnormal tone, lowbody temperature, seizure[s]), OR

  • Meeting the criteria of MDE definition, OR

  • Evidence of laboratory abnormalities as evidenced by at least one of thefollowing:

  • Metabolic acidosis with elevated anion gap.

  • Acute hyperammonemia.

  • Neutropenia or thrombocytopenia.

Exclusion

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 theInvestigator or Sponsor's opinion that could interfere with or limit theparticipation in the study.

  • Estimated glomerular filtration rate (eGFR) <30 milliliters (mL)/minute/1.73 squaremeter (m^2) for participants of all ages receiving chronic dialysis.

  • History of organ transplantation or planned organ transplantation during the periodof 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 FailureClassification for Children or the New York Heart Association Classification.

  • Pregnant or breastfeeding.

  • Other clinically significant conditions that in the Investigator's opinion couldinterfere with the safety of the participant, the interpretation of study results,or limit the participation in the study.

Study Design

Total Participants: 77
Treatment Group(s): 1
Primary Treatment: mRNA-3927
Phase: 1/2
Study Start date:
April 15, 2021
Estimated Completion Date:
January 31, 2026

Study Description

During the Dose Optimization Stage, after each dose cohort is fully enrolled (≥1 year of age), and the dose-limiting toxicity (DLT) observation window of at least 14 days is complete for the final participant in that cohort, 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 9 cohorts will be enrolled in Part 1 (Dose Optimization).

Upon establishment of a dose with an acceptable safety and PD activity in Part 1 (participants ≥1 year of age), additional participants will be enrolled into the study in Part 2 (participants ≥1 year of age) to allow for determination of the safety, efficacy, and PD of mRNA-3927. Part 3 will evaluate the safety, efficacy and PD response in infants (<1 year of age).

Participants in all the phases will participate in a predosing observational period, followed by a treatment period, and then a follow-up period after withdrawal of treatment.

Connect with a study center

  • Stollery Children's Hospital University of Alberta

    Edmonton, Alberta T6G 2R7
    Canada

    Site Not Available

  • Stollery Children's Hospital University of Alberta

    Edmonton 5946768, Alberta 5883102 T6G 2R7
    Canada

    Active - Recruiting

  • Hospital For Sick Children

    Toronto, Ontario M5G 1X8
    Canada

    Site Not Available

  • Hospital For Sick Children

    Toronto 6167865, Ontario 6093943 M5G 1X8
    Canada

    Active - Recruiting

  • CHU de Marseille - Hôpital de la Timone

    Marseille, 13005
    France

    Site Not Available

  • CHU de Marseille - Hôpital de la Timone

    Marseille 2995469, 13005
    France

    Site Not Available

  • Hôpital Necker - Enfants Malades

    Paris, 75019
    France

    Site Not Available

  • Hôpital Necker - Enfants Malades

    Paris 2988507, 75019
    France

    Active - Recruiting

  • Fujita Health University Hospital

    Toyoake-shi, Aichi-ken 1865694 470-1192
    Japan

    Active - Recruiting

  • Tohoku University Hospital

    Sendai-Shi, Miyagi 980-8574
    Japan

    Site Not Available

  • Tohoku University Hospital

    Sendai 2111149, Miyagi 2111888 980-8574
    Japan

    Active - Recruiting

  • National Center for Child Health and Development

    Tokyo, 113-8519
    Japan

    Site Not Available

  • National Center for Child Health and Development

    Tokyo 1850147, 113-8519
    Japan

    Site Not Available

  • Erasmus MC

    Rotterdam 2747891, South Holland 2743698 3015 GD
    Netherlands

    Active - Recruiting

  • Erasmus MC

    Rotterdam, Zuid-Holland 3015 GD
    Netherlands

    Site Not Available

  • Universitair Medisch Centrum Utrecht - PPDS

    Utrecht, 3584 CX
    Netherlands

    Site Not Available

  • Universitair Medisch Centrum Utrecht - PPDS

    Utrecht 2745912, 3584 CX
    Netherlands

    Site Not Available

  • King Abdullah Children's Specialist Hospital

    Riyadh, Ar Riya 14611
    Saudi Arabia

    Site Not Available

  • King Fahad Medical City

    Riyadh, Ar Riya 11564
    Saudi Arabia

    Site Not Available

  • King Faisal Specialist Hospital & Research Center - Riyadh

    Riyadh, Ar Riya 11211
    Saudi Arabia

    Site Not Available

  • King Abdullah Children's Specialist Hospital

    Riyadh 108410, Ar Riya 14611
    Saudi Arabia

    Site Not Available

  • King Fahad Medical City

    Riyadh 108410, Ar Riya 11564
    Saudi Arabia

    Site Not Available

  • King Faisal Specialist Hospital & Research Center - Riyadh

    Riyadh 108410, Ar Riya 11211
    Saudi Arabia

    Site Not Available

  • Hospital Sant Joan de Deu - PIN

    Esplugues de Llobregat, Barcelona 8950
    Spain

    Site Not Available

  • Hospital Sant Joan de Deu - PIN

    Esplugues de Llobregat 3122826, Barcelona 8950
    Spain

    Site Not Available

  • Hospital Universitario Cruces

    Barakaldo, Biscay 48903
    Spain

    Site Not Available

  • Hospital Universitario Cruces

    Barakaldo 3109453, Biscay 48903
    Spain

    Active - Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041
    Spain

    Site Not Available

  • Hospital Universitario 12 de Octubre

    Madrid 3117735, 28041
    Spain

    Active - Recruiting

  • Hospital Universitario Virgen del Rocio - PPDS

    Sevilla, 41013
    Spain

    Site Not Available

  • Hospital Universitario Virgen del Rocio - PPDS

    Seville 2510911, 41013
    Spain

    Site Not Available

  • Birmingham Children's Hospital

    Birmingham, B4 6NH
    United Kingdom

    Completed

  • University Hospital Birmingham NHS Foundation Trust

    Birmingham, B15 2TH
    United Kingdom

    Site Not Available

  • Birmingham Children's Hospital

    Birmingham 2655603, B4 6NH
    United Kingdom

    Completed

  • University Hospital Birmingham NHS Foundation Trust

    Birmingham 2655603, B15 2TH
    United Kingdom

    Active - Recruiting

  • Great Ormond Street Hospital (GOSH)

    London, WC1N 3JH
    United Kingdom

    Active - Recruiting

  • Great Ormond Street Hospital for Children NHS Foundation Trust

    London, WC1N 3JH
    United Kingdom

    Site Not Available

  • Great Ormond Street Hospital for Children NHS Foundation Trust

    London 2643743, WC1N 3JH
    United Kingdom

    Active - Recruiting

  • Manchester University NHS Foundation Trust

    Manchester, M13 9WL
    United Kingdom

    Active - Recruiting

  • Willink Biochemical Genetics Unit

    Manchester, M13 9WL
    United Kingdom

    Active - Recruiting

  • Willink Biochemical Genetics Unit - PPDS

    Manchester, M13 9WL
    United Kingdom

    Site Not Available

  • Willink Biochemical Genetics Unit - PPDS

    Manchester 2643123, M13 9WL
    United Kingdom

    Active - Recruiting

  • David Geffen School of Medicine UCLA

    Los Angeles, California 90095
    United States

    Active - Recruiting

  • Ronald Reagan UCLA Medical Center

    Los Angeles, California 90095
    United States

    Active - Recruiting

  • UCSD Altman Clinical and Transalational Research Institute Building

    Los Angeles, California 90027
    United States

    Site Not Available

  • Lucile Packard Children's Hospital Stanford

    Stanford, California 94304
    United States

    Site Not Available

  • University of Stanford Medical Center

    Stanford, California 94304
    United States

    Active - Recruiting

  • Ronald Reagan UCLA Medical Center

    Los Angeles 5368361, California 5332921 90095
    United States

    Active - Recruiting

  • UCSD Altman Clinical and Transalational Research Institute Building

    Los Angeles 5368361, California 5332921 90027
    United States

    Site Not Available

  • Lucile Packard Children's Hospital Stanford

    Stanford 5398563, California 5332921 94304
    United States

    Active - Recruiting

  • Nicklaus Children's Hospital

    Miami, Florida 33155
    United States

    Site Not Available

  • University of South Florida - 12901 Bruce B Downs

    Tampa, Florida 33606-3603
    United States

    Site Not Available

  • Nicklaus Children's Hospital

    Miami 4164138, Florida 4155751 33155
    United States

    Site Not Available

  • University of South Florida - 12901 Bruce B Downs

    Tampa 4174757, Florida 4155751 33606-3603
    United States

    Site Not Available

  • Ann and Robert H Lurie Childrens Hospital of Chicago

    Chicago 4887398, Illinois 4896861 60611
    United States

    Active - Recruiting

  • Johns Hopkins Hospital

    Baltimore, Maryland 21287
    United States

    Active - Recruiting

  • Johns Hopkins Hospital, Adult Outpatient Clinical Research Unit

    Baltimore, Maryland 21287
    United States

    Site Not Available

  • Johns Hopkins Hospital, Adult Outpatient Clinical Research Unit

    Baltimore 4347778, Maryland 4361885 21287
    United States

    Completed

  • Boston Children's Hospital

    Boston, Massachusetts 02115
    United States

    Site Not Available

  • Boston Children's Hospital

    Boston 4930956, Massachusetts 6254926 02115
    United States

    Completed

  • University of Michigan

    Ann Arbor, Michigan 48109
    United States

    Active - Recruiting

  • University of Michigan Hospitals

    Ann Arbor, Michigan 48109
    United States

    Site Not Available

  • University of Michigan Hospitals

    Ann Arbor 4984247, Michigan 5001836 48109
    United States

    Active - Recruiting

  • Icahn School of Medicine at Mount Sinai - Clinical Research Unit

    New York, New York 10029
    United States

    Site Not Available

  • Icahn School of Medicine at Mount Sinai - Clinical Research Unit

    New York 5128581, New York 5128638 10029
    United States

    Active - Recruiting

  • Duke University Medical Center

    Durham, North Carolina 27710
    United States

    Active - Recruiting

  • Duke University Medical System (Duke Health)

    Durham, North Carolina 27710
    United States

    Site Not Available

  • Duke University Medical System (Duke Health)

    Durham 4464368, North Carolina 4482348 27710
    United States

    Active - Recruiting

  • Ann and Robert H Lurie Childrens Hospital of Chicago

    Cincinnati, Ohio 45229-3026
    United States

    Site Not Available

  • Cincinnati Children's Hospital

    Cincinnati, Ohio 45229
    United States

    Active - Recruiting

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio 45229
    United States

    Completed

  • University Hospitals Cleveland Medical Center - 11100 Euclid Ave

    Cleveland, Ohio 44106-2624
    United States

    Site Not Available

  • Cincinnati Children's Hospital Medical Center

    Cincinnati 4508722, Ohio 5165418 45229
    United States

    Completed

  • University Hospitals Cleveland Medical Center - 11100 Euclid Ave

    Cleveland 5150529, Ohio 5165418 44106-2624
    United States

    Site Not Available

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • Children's Hospital of Philadelphia (CHOP)

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • Children's Hospital of Philadelphia (CHOP)

    Philadelphia 4560349, Pennsylvania 6254927 19104
    United States

    Active - Recruiting

  • Texas Children's Hospital

    Houston, Texas 77030
    United States

    Site Not Available

  • Texas Children's Hospital

    Houston 4699066, Texas 4736286 77030
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.