A Phase 1/2 interventional study of mRNA-3927 in Propionic Acidemia, sponsored by ModernaTX, Inc.. Recruiting at 35 sites in 8 countries. Per ClinicalTrials.gov, last updated 2026-01-22.
Sponsored by ModernaTX, Inc. (part of Moderna, Inc.) · Phase 1/2, Interventional, and Treatment
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).
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.
23 studies on the registry are indexed under Propionic Acidemia; 8 are open to participants now.
This study's planned enrollment of 77 is above the median of 30 across 12 interventional studies indexed under Propionic Acidemia.
Browse Propionic Acidemia studies →ModernaTX, Inc. is the lead sponsor of 119 studies on the registry; 18 are open to participants now.
Of its 64 completed or terminated interventional studies of FDA-regulated products, 35 (55%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Participants ≥1 year of age are eligible to be included in the study only if all of the following criteria apply:
Participants \<1 Year of Age :
At least 1 documented PA-related event prior to Screening defined as the following criteria:
Exclusion Criteria:
Participants of all ages are excluded from the study if during Screening any of the following criteria apply:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Biological: mRNA-3927
mRNA-3927 dispersion for IV infusion
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
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
Time frame: Baseline up to Week 40
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
Time frame: Baseline up to Week 40
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
Time frame: Baseline up to Week 40
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
Time frame: Baseline up to Week 40
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
Time frame: Baseline up to Week 40
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
Time frame: Baseline up to Week 40
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
Time frame: Baseline up to Week 40
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
Time frame: Baseline up to Week 40
Part 1: Frequency of Anti-Polyethylene Glycol and Anti-Propionyl-CoA Carboxylase Antibodies
Time frame: Day 1 (initial mRNA-3927 dose) up to Week 150 (End of Study)
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
Time frame: Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 12
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
Time frame: Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 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
Time frame: Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 12
Parts 2 and 3: Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Score and Physical Function Score
Time frame: Baseline up to Week 52
Parts 2 and 3: Change from Baseline in Methylmalonic Acidemia and Propionic Acidemia Questionnaire - Proximal Signs and Symptoms (MMAPAQ-PSS) Total Score
Time frame: Baseline up to Week 52
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
Time frame: Baseline up to Week 52
Parts 2 and 3: Percentage of Participants Meeting 'Modestly Improved' or 'Much Improved' in Investigator Global Assessment of Improvement (IGA-I)
Time frame: Baseline up to Week 52
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
Time frame: Pretreatment period (12 months before consent to first mRNA-3927 dose in the study) up to Month 12
Parts 2 and 3: Change From Baseline in Plasma 2-MC and 3-HP Levels After Administration of mRNA-3927
Time frame: Baseline up to Week 52
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
Time frame: Baseline up to Week 52
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
Time frame: Baseline up to Week 52
Parts 2 and 3: Emax of 2-MC and 3-HP After Administration of mRNA-3927
Time frame: Baseline up to Week 52
Part 2: Number of Participants with TEAEs, SAEs, AESIs, and TEAEs Leading to Discontinuation
Time frame: Day 1 up to Week 73
Part 3: Annualized Frequency of CEC-adjudicated MDEs
Time frame: Baseline up to Week 52
Part 3: Annualized Frequency of CEC-adjudicated MDE-related Hospitalizations
Time frame: Baseline up to Week 52
Part 3: Annualized Frequency of CEC-adjudicated PA-related Hospitalizations
Time frame: Baseline up to Week 52
Part 3: Annualized Frequency of CEC-adjudicated MDEs by the Following MDE Severity Grades: Grade 1, Grade 2, Grade 3
Time frame: Baseline up to Week 52
Part 3: Annualized Frequency of CEC-adjudicated PA-related Urgent Healthcare Encounters
Time frame: Baseline up to Week 52
Part 3: Cmax of PCCA and PCCB mRNAs
Time frame: Baseline up to Week 52
Part 3: Tmax of PCCA and PCCB mRNAs
Time frame: Baseline up to Week 52
Part 3: AUC of PCCA and PCCB mRNAs
Time frame: Baseline up to Week 52
Part 3: Cmax of SM-86 and OL-56
Time frame: Baseline up to Week 52
Part 3: Tmax of SM-86 and OL-56
Time frame: Baseline up to Week 52
Part 3: AUC of SM-86 and OL-56
Time frame: Baseline up to Week 52
Not enrolling at this site — choose another above.
Not enrolling at this site — choose another above.
Not enrolling at this site — choose another above.
Not enrolling at this site — choose another above.
Not enrolling at this site — choose another above.
Not enrolling at this site — choose another above.
Not enrolling at this site — choose another above.
Not enrolling at this site — choose another above.
Not enrolling at this site — choose another above.
Not enrolling at this site — choose another above.
Not enrolling at this site — choose another above.
Plan to share: No
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.