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Propionic AcidemiaPhase 1/2NCT04159103

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

A Phase 1/2 study testing mRNA-3927 in people with Propionic Acidemia, run by ModernaTX, Inc. at 35 sites in 8 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Any age
Conditions the study is for
Propionic Acidemia
What is being tested?
mRNA-3927
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
35 sitesin 8 countries
Study dates
15 Apr 2021to 31 Aug 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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 :
Show all 16Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

35 sites in 8 countries. Contact the study team or a site near you to ask about taking part.

Moderna WeCare Team contact

1-866-663-3762

WeCareClinicalTrials@modernatx.com

35 sites in 8 countries

United States15 sites, 11 recruiting

  • University of Michigan Hospitals

    Ann Arbor, Michigan, 48109

    Recruiting

  • Johns Hopkins Hospital, Adult Outpatient Clinical Research Unit

    Baltimore, Maryland, 21287

    Completed

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

    Completed

  • Ann and Robert H Lurie Childrens Hospital of Chicago

    Chicago, Illinois, 60611

    Recruiting

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

    Completed

  • University Hospitals Cleveland Medical Center - 11100 Euclid Ave

    Cleveland, Ohio, 44106-2624

    Active, not recruiting

  • Duke University Medical System (Duke Health)

    Durham, North Carolina, 27710

    Ming Xu, mingfen.xu@duke.edu

    Recruiting

  • Texas Children's Hospital

    Houston, Texas, 77030

    Alyssa Tran, alyssat@bcm.edu

    Recruiting

  • UCSD Altman Clinical and Transalational Research Institute Building

    Los Angeles, California, 90027

    Not yet recruiting

  • Ronald Reagan UCLA Medical Center

    Los Angeles, California, 90095

    Rosemary Silva-Garcia, rsilvagarcia@mednet.ucla.edu

    Recruiting

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

    Not yet recruiting

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

    New York, New York, 10029

    Recruiting

  • Children's Hospital of Philadelphia (CHOP)

    Philadelphia, Pennsylvania, 19104

    Rebecca Madden, maddenr@chop.edu

    Recruiting

  • Lucile Packard Children's Hospital Stanford

    Stanford, California, 94304

    650-497-0454, hsrobin@stanford.edu

    Recruiting

  • University of South Florida - 12901 Bruce B Downs

    Tampa, Florida, 33606-3603

    Not yet recruiting

Other trials in United States

Spain4 sites, 2 recruiting

  • Hospital Universitario Cruces

    Barakaldo, Biscay, 48903

    Recruiting

  • Hospital Sant Joan de Deu - PIN

    Esplugues de Llobregat, Barcelona, 8950

    Active, not recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

    Recruiting

  • Hospital Universitario Virgen del Rocio - PPDS

    Seville, 41013

    Active, not recruiting

Other trials in Spain

United Kingdom4 sites, 3 recruiting

  • University Hospital Birmingham NHS Foundation Trust

    Birmingham, B15 2TH

    Vishy Veeranna, Vishy.veeranna@uhb.nhs.uk

    Recruiting

  • Birmingham Children's Hospital

    Birmingham, B4 6NH

    Completed

  • Great Ormond Street Hospital for Children NHS Foundation Trust

    London, WC1N 3JH

    Stephanie.Grunewald@gosh.nhs.uk

    Stephanie Grunewald

    Recruiting

  • Willink Biochemical Genetics Unit - PPDS

    Manchester, M13 9WL

    Recruiting

Other trials in United Kingdom

Japan3 sites, 2 recruiting

  • Tohoku University Hospital

    Sendai, Miyagi, 980-8574

    natsuko.ichinoi.b6@tohoku.ac.jp

    Natsuko Ichinoi

    Recruiting

  • National Center for Child Health and Development

    Tokyo, 113-8519

    Active, not recruiting

  • Fujita Health University Hospital

    Toyoake-shi, Aichi-ken, 470-1192

    yonaka@fujita-hu.ac.jp

    Yoko Nakajima

    Recruiting

Other trials in Japan

Saudi Arabia3 sites, 2 recruiting

  • King Faisal Specialist Hospital & Research Center - Riyadh

    Riyadh, Ar Riya, 11211

    Active, not recruiting

  • King Fahad Medical City

    Riyadh, Ar Riya, 11564

    Not yet recruiting

  • King Abdullah Children's Specialist Hospital

    Riyadh, Ar Riya, 14611

    Not yet recruiting

Other trials in Saudi Arabia

Canada2 sites, 2 recruiting

  • Stollery Children's Hospital University of Alberta

    Edmonton, Alberta, T6G 2R7

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

    Komudi Siriwardena

    Recruiting

  • Hospital For Sick Children

    Toronto, Ontario, M5G 1X8

    Ashley Wilson, ashley.wilson@sickkids.ca

    Recruiting

Other trials in Canada

France2 sites, 1 recruiting

  • CHU de Marseille - Hôpital de la Timone

    Marseille, 13005

    Active, not recruiting

  • Hôpital Necker - Enfants Malades

    Paris, 75019

    Recruiting

Other trials in France

Netherlands2 sites, 1 recruiting

  • Erasmus MC

    Rotterdam, South Holland, 3015 GD

    Recruiting

  • Universitair Medisch Centrum Utrecht - PPDS

    Utrecht, 3584 CX

    Active, not recruiting

Other trials in Netherlands

About this study

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

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).

Read the detailed 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.

Being tested
mRNA-3927
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
Medical subject headings
Propionic Acidemia, Metabolism, Inborn Errors, Genetic Diseases, Inborn, Amino Acid Metabolism, Inborn Errors, Acidosis, Acid-Base Imbalance, Metabolic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • mRNA-3927Biological

    mRNA-3927 dispersion for IV infusion

Study groups in NCT04159103
Study groupRoleWhat they receive
Part 1 (Dose Optimization), Part 2 (Pivotal Study), and Part 3 (Infants)ExperimentalPart 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.
Receives: Biological: mRNA-3927

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Number of Participants with Treatment-emergent Adverse Event (TEAE), Serious Adverse Events (SAE) and TEAEs Leading to Discontinuation

    Measured: Day 1 (initial mRNA-3927 dose) up to Week 150 (End of Study)

  2. 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

    Measured: Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 12

  3. Part 3: Number of Participants with TEAEs, SAEs, Adverse Events (AEs) of Special Interest (AESIs) and TEAEs Leading to Discontinuation

    Measured: Day 1 up to Week 73

Secondary outcomes (33)

  1. Part 1: Change From Baseline in Plasma 2-Methylcitrate (2-MC) and 3-Hydroxypropionic Acid (3-HP) Levels After Single and Repeated Administrations of mRNA-3927

    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

    Measured: Baseline up to Week 40

  2. Part 1: Maximum Observed Effect (Emax) of 2-MC and 3-HP After Single and Repeated Administrations of mRNA-3927

    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

    Measured: Baseline up to Week 40

  3. Part 1: Area Under the Effect Versus Time Curve (AUEC) of 2-MC and 3-HP After Single and Repeated Administrations of mRNA-3927

    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

    Measured: Baseline up to Week 40

  4. Part 1: Duration of Response (DOR) After Single and Repeated Administrations of mRNA-3927

    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

    Measured: Baseline up to Week 40

  5. Part 1: Maximum Observed Concentration (Cmax) of Propionyl-CoA Carboxylase Subunit α (PCCA) and Propionyl-CoA Carboxylase Subunit β (PCCB) mRNAs

    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

    Measured: Baseline up to Week 40

  6. Part 1: Time of Cmax (Tmax) of PCCA and PCCB mRNAs

    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

    Measured: Baseline up to Week 40

  7. Part 1: Area Under the Plasma Concentration-Time Curve (AUC) of PCCA and PCCB mRNAs

    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

    Measured: Baseline up to Week 40

  8. Part 1: SM-86 Concentration After Single and Repeated Administrations of mRNA-3927

    Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927

    Measured: Baseline up to Week 40

  9. Part 1: Frequency of Anti-Polyethylene Glycol and Anti-Propionyl-CoA Carboxylase Antibodies

    Measured: Day 1 (initial mRNA-3927 dose) up to Week 150 (End of Study)

  10. Part 2: Change in Annualized Frequency of CEC-adjudicated MDE-related Hospitalizations During the 12-month Treatment Period With mRNA-3927 Compared to the Annualized Frequency of CEC-adjudicated MDE-related Hospitalizations During the Pretreatment Period

    Measured: Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 12

  11. Part 2: Change in Annualized Frequency of CEC-adjudicated PA-related Hospitalizations During the 12-month Treatment Period With mRNA-3927 Compared to the Annualized Frequency of CEC-adjudicated PA-related Hospitalizations During the Pretreatment Period

    Measured: Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 12

  12. Part 2: Change in Annualized Frequency of CEC-adjudicated MDEs During 12-month Treatment Period With mRNA-3927 Compared to Annualized Frequency of CEC-adjudicated MDE During Pretreatment Period by the Following Severity Grades: Grade 1, Grade 2, Grade 3

    Measured: Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 12

  13. Parts 2 and 3: Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Score and Physical Function Score

    Measured: Baseline up to Week 52

  14. Parts 2 and 3: Change from Baseline in Methylmalonic Acidemia and Propionic Acidemia Questionnaire - Proximal Signs and Symptoms (MMAPAQ-PSS) Total Score

    Measured: Baseline up to Week 52

  15. Parts 2 and 3: Percentage of Participants Distributed into 'Mild', 'Moderate', and 'Severe' Categories Based on Investigator Global Assessment of Severity (IGA-S) Severity Levels

    Measured: Baseline up to Week 52

  16. Parts 2 and 3: Percentage of Participants Meeting 'Modestly Improved' or 'Much Improved' in Investigator Global Assessment of Improvement (IGA-I)

    Measured: Baseline up to Week 52

  17. Part 2: Change in Annualized Frequency of CEC-adjudicated PA-related Urgent Healthcare Encounters During 12-month Treatment Period Compared to Annualized Frequency of CEC-adjudicated PA-related Urgent Healthcare Encounters During Pretreatment Period

    Measured: Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 12

  18. Parts 2 and 3: Change From Baseline in Plasma 2-MC and 3-HP Levels After Administration of mRNA-3927

    Measured: Baseline up to Week 52

  19. Parts 2 and 3: Area That is Below the Baseline and Above the Response Curve (AUC_Below_B) of 2-MC and 3-HP After Administration of mRNA-3927

    Measured: Baseline up to Week 52

  20. Parts 2 and 3: Area Under the Curve That is AUC_Above_B - AUC_Below_B (AUC_Net_B) of 2-MC and 3-HP After Administration of mRNA-3927

    Measured: Baseline up to Week 52

  21. Parts 2 and 3: Emax of 2-MC and 3-HP After Administration of mRNA-3927

    Measured: Baseline up to Week 52

  22. Part 2: Number of Participants with TEAEs, SAEs, AESIs, and TEAEs Leading to Discontinuation

    Measured: Day 1 up to Week 73

  23. Part 3: Annualized Frequency of CEC-adjudicated MDEs

    Measured: Baseline up to Week 52

  24. Part 3: Annualized Frequency of CEC-adjudicated MDE-related Hospitalizations

    Measured: Baseline up to Week 52

  25. Part 3: Annualized Frequency of CEC-adjudicated PA-related Hospitalizations

    Measured: Baseline up to Week 52

  26. Part 3: Annualized Frequency of CEC-adjudicated MDEs by the Following MDE Severity Grades: Grade 1, Grade 2, Grade 3

    Measured: Baseline up to Week 52

  27. Part 3: Annualized Frequency of CEC-adjudicated PA-related Urgent Healthcare Encounters

    Measured: Baseline up to Week 52

  28. Part 3: Cmax of PCCA and PCCB mRNAs

    Measured: Baseline up to Week 52

  29. Part 3: Tmax of PCCA and PCCB mRNAs

    Measured: Baseline up to Week 52

  30. Part 3: AUC of PCCA and PCCB mRNAs

    Measured: Baseline up to Week 52

  31. Part 3: Cmax of SM-86 and OL-56

    Measured: Baseline up to Week 52

  32. Part 3: Tmax of SM-86 and OL-56

    Measured: Baseline up to Week 52

  33. Part 3: AUC of SM-86 and OL-56

    Measured: Baseline up to Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2019
  2. Study start15 Apr 2021
  3. Primary completion31 Aug 2027 (estimated)
  4. Study completion31 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
77 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04159103
Sponsor's protocol ID
mRNA-3927-P101
Other IDs
2022-502910-10-00
Status last verified
Jan 2026
First submitted
7 Nov 2019
Last updated
22 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Attarwala H, Lumley M, Liang M, Ivaturi V, Senn J. Translational Pharmacokinetic/Pharmacodynamic Model for mRNA-3927, an Investigational Therapeutic for the Treatment of Propionic Acidemia. Nucleic Acid Ther. 2023 Apr;33(2):141-147. doi: 10.1089/nat.2022.0036. Epub 2022 Dec 27.

    PubMed 36577040

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing mRNA-3927 in people with Propionic Acidemia, run by ModernaTX, Inc. at 35 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, Spain, United Kingdom, Japan, Saudi Arabia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Moderna WeCare Team (1-866-663-3762, WeCareClinicalTrials@modernatx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04159103, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2026.

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