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Looking for participantsPhase1/Phase2

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

Sponsor: ModernaTX, Inc.

NCT ID: NCT04159103

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
mRNA-3927 (biological)
How long the study runs
Study runs about 76 months (dates as stated)
About the drug or intervention
mRNA-3927 — biological: mRNA-3927 dispersion for IV infusion
Patient visit burden
Not specified by the sponsor

In plain English

This is an open-label study of a medicine called mRNA-3927 in people with propionic acidemia (PA), a rare inherited condition affecting how the body breaks down certain fats and proteins. 'Open-label' means everyone who takes part knows they are receiving the study medicine. The study is run by ModernaTX, Inc.

Who can take part

  • People aged 1 year or older with propionic acidemia confirmed by genetic testing showing PCCA and/or PCCB changes.
  • The first 2 people joining Part 1 must be at least 8 years old when they agree to take part.
  • For Part 2 only: at least one documented metabolic decompensation event (a serious metabolic crisis) in the 12 months before agreeing to take part.
  • Babies under 1 year may join if PA is picked up by newborn screening, or suspected because of metabolic symptoms plus a sibling with PA. They can start screening while waiting for genetic test results, but can only be enrolled once PA is confirmed.
  • Babies in neonatal intensive care (NICU) must have been born after at least 37 weeks of pregnancy, with no other conditions that could affect the study results.
  • Babies must weigh at least 3 kilograms at screening.
  • Babies must have had at least one PA-related event before screening, such as signs of metabolic deterioration, a metabolic decompensation event, or certain abnormal lab results (metabolic acidosis with high anion gap, high ammonia in the blood, or low white cells or platelets).

Who may not be able to

  • Lab results that are clearly abnormal and judged by the study doctor or sponsor to interfere with taking part or understanding the results.
  • An estimated glomerular filtration rate (a measure of kidney function) below 30 mL/min/1.73m², or being on long-term dialysis.
  • Having had, or planning, an organ transplant during the study.
  • A corrected QT heart rhythm measurement above 480 milliseconds.
  • Grade 3 or 4 heart failure.
  • Being pregnant or breastfeeding.
  • Any other condition that, in the study doctor's opinion, could affect safety, interfere with the results, or limit taking part.

What taking part involves

  • • Taking the study medicine mRNA-3927 — how it is given is not stated — ask the trial team.
  • • Attending screening visits to check eligibility, which for babies includes checks on weight and lab results.
  • • Part 2 participants will have had their metabolic events recorded before joining.

Time commitment: Not stated — ask the trial team.

Plain-English summary (AI-generated) from registry data. Not eligibility advice — only the trial team can confirm whether you can take part. Use the eligibility checker to see how your health profile matches this trial.

Type of study
Testing a treatment
Ages
Not specified
Who
All
Number of participants
77
Started
2021-04-15
Last checked
2026-01

Plain English Summary

What is this study?

  • • Testing a new treatment for propionic acidemia
  • • Phase1/Phase2 - 77 participants
  • • 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)

Who can take part?

  • • Adults
  • • Diagnosed with propionic acidemia

Where?

  • • Birmingham - University Hospital Birmingham NHS Foundation Trust
  • • Birmingham - Birmingham Children's Hospital
  • • London - Great Ormond Street Hospital for Children NHS Foundation Trust
  • • Manchester - Willink Biochemical Genetics Unit - PPDS

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

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).

More detail

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.

Propionic Acidemia

How this trial compares with your answers

Answer 2 more questions to improve match

What we know so far

Condition· Matched your search
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Still need:

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Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: Not specified
  • Who can join: All genders

Biomarkers mentioned

meteGFR

What the study is looking for

  • ✓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...
  • ✓Part 2 only: At least one documented MDE in the 12-month period before consent.

Who cannot take part

  • ✗Participants of all ages are excluded from the study if during Screening any of the following criteria apply:
  • ✗Estimated glomerular filtration rate (eGFR) \<30 milliliters (mL)/minute/1.73 square meter (m\^2) for participants...
  • ✗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...
See the full 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 Is This Study? (4 UK sites)

University Hospital Birmingham NHS Foundation Trust

Birmingham B15 2TH, United Kingdom

Recruiting
Site contact (verified)

Birmingham Children's Hospital

Birmingham B4 6NH, United Kingdom

COMPLETED
Hospital R&D contact (matched)

Sarah Pountain Head of Research Governance

R&D@uhb.nhs.uk0121 371 4185

Great Ormond Street Hospital for Children NHS Foundation Trust

London WC1N 3JH, United Kingdom

Recruiting
Site contact (verified)
Stephanie GrunewaldPrincipal Investigator

Willink Biochemical Genetics Unit - PPDS

Manchester M13 9WL, United Kingdom

Recruiting

How to Get in Touch

Moderna WeCare Team

Sponsor contact

CONTACT

1-866-663-3762 WeCareClinicalTrials@modernatx.com
Data sourced from ClinicalTrials.gov · Last verified: 2026-01