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

NCT ID: NCT04159103

Last Updated: 2025-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

77 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-15

Study Completion Date

2026-01-31

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Propionic Acidemia

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

mRNA-3927

Intervention Type BIOLOGICAL

mRNA-3927 dispersion for IV infusion

Interventions

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mRNA-3927

mRNA-3927 dispersion for IV infusion

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ModernaTX, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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UCSD Altman Clinical and Transalational Research Institute Building

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Lucile Packard Children's Hospital Stanford

Stanford, California, United States

Site Status RECRUITING

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status NOT_YET_RECRUITING

University of South Florida - 12901 Bruce B Downs

Tampa, Florida, United States

Site Status NOT_YET_RECRUITING

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, United States

Site Status RECRUITING

Johns Hopkins Hospital, Adult Outpatient Clinical Research Unit

Baltimore, Maryland, United States

Site Status COMPLETED

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status COMPLETED

University of Michigan Hospitals

Ann Arbor, Michigan, United States

Site Status RECRUITING

Icahn School of Medicine at Mount Sinai - Clinical Research Unit

New York, New York, United States

Site Status RECRUITING

Duke University Medical System (Duke Health)

Durham, North Carolina, United States

Site Status RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status COMPLETED

University Hospitals Cleveland Medical Center - 11100 Euclid Ave

Cleveland, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Texas Children's Hospital

Houston, Texas, United States

Site Status RECRUITING

Stollery Children's Hospital University of Alberta

Edmonton, Alberta, Canada

Site Status RECRUITING

Hospital For Sick Children

Toronto, Ontario, Canada

Site Status RECRUITING

CHU de Marseille - Hôpital de la Timone

Marseille, , France

Site Status ACTIVE_NOT_RECRUITING

Hôpital Necker - Enfants Malades

Paris, , France

Site Status RECRUITING

Fujita Health University Hospital

Toyoake-shi, Aichi-ken, Japan

Site Status RECRUITING

Tohoku University Hospital

Sendai, Miyagi, Japan

Site Status RECRUITING

National Center for Child Health and Development

Tokyo, , Japan

Site Status ACTIVE_NOT_RECRUITING

Erasmus MC

Rotterdam, South Holland, Netherlands

Site Status RECRUITING

Universitair Medisch Centrum Utrecht - PPDS

Utrecht, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

King Faisal Specialist Hospital & Research Center - Riyadh

Riyadh, Ar Riya, Saudi Arabia

Site Status ACTIVE_NOT_RECRUITING

King Fahad Medical City

Riyadh, Ar Riya, Saudi Arabia

Site Status NOT_YET_RECRUITING

King Abdullah Children's Specialist Hospital

Riyadh, Ar Riya, Saudi Arabia

Site Status NOT_YET_RECRUITING

Hospital Sant Joan de Deu - PIN

Esplugues de Llobregat, Barcelona, Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital Universitario Cruces

Barakaldo, Biscay, Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocio - PPDS

Seville, , Spain

Site Status ACTIVE_NOT_RECRUITING

University Hospital Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status RECRUITING

Birmingham Children's Hospital

Birmingham, , United Kingdom

Site Status COMPLETED

Great Ormond Street Hospital for Children NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Willink Biochemical Genetics Unit - PPDS

Manchester, , United Kingdom

Site Status RECRUITING

Countries

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United States Canada France Japan Netherlands Saudi Arabia Spain United Kingdom

Central Contacts

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Moderna WeCare Team

Role: CONTACT

1-866-663-3762

Facility Contacts

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Rosemary Silva-Garcia

Role: primary

Role: primary

650-497-0454

Ming Xu

Role: primary

Rebecca Madden

Role: primary

Alyssa Tran

Role: primary

Cheri Robert

Role: primary

(780) 248-5611

Ashley Wilson

Role: primary

Role: primary

Role: primary

Vishy Veeranna

Role: primary

Role: primary

References

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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.

Reference Type DERIVED
PMID: 36577040 (View on PubMed)

Other Identifiers

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2022-502910-10-00

Identifier Type: OTHER

Identifier Source: secondary_id

mRNA-3927-P101

Identifier Type: -

Identifier Source: org_study_id

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