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

NCT04159103 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: mRNA-3927-P1012022-502910-10-00
• Study Type: interventional
• Target: 77
• Locations: 8 countries
• Sites: 35

Brief 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).

Conditions

Propionic Acidemia

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

Outcome Measures

Primary Outcomes (3)

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

  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

  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

  Day 1 up to Week 73

Secondary Outcomes (33)

• 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 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 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 up to Week 40

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

  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 up to Week 40

Study Arms (1)

Part 1 (Dose Optimization), Part 2 (Pivotal Study), and Part 3 (Infants)

EXPERIMENTAL

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

Interventions

mRNA-3927 BIOLOGICAL

mRNA-3927 dispersion for IV infusion

Part 1 (Dose Optimization), Part 2 (Pivotal Study), and Part 3 (Infants)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ModernaTX, Inc.: lead

Study Sites (35)

UCSD Altman Clinical and Transalational Research Institute Building

Los Angeles, California, 90027, United States

NOT YET RECRUITING

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

RECRUITING

Lucile Packard Children's Hospital Stanford

Stanford, California, 94304, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

NOT YET RECRUITING

University of South Florida - 12901 Bruce B Downs

Tampa, Florida, 33606-3603, United States

NOT YET RECRUITING

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Johns Hopkins Hospital, Adult Outpatient Clinical Research Unit

Baltimore, Maryland, 21287, United States

COMPLETED

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

COMPLETED

University of Michigan Hospitals

Ann Arbor, Michigan, 48109, United States

RECRUITING

Icahn School of Medicine at Mount Sinai - Clinical Research Unit

New York, New York, 10029, United States

RECRUITING

Duke University Medical System (Duke Health)

Durham, North Carolina, 27710, United States

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

ACTIVE NOT RECRUITING

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Stollery Children's Hospital University of Alberta

Edmonton, Alberta, T6G 2R7, Canada

RECRUITING

Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

CHU de Marseille - Hôpital de la Timone

Marseille, 13005, France

ACTIVE NOT RECRUITING

Hôpital Necker - Enfants Malades

Paris, 75019, France

RECRUITING

Fujita Health University Hospital

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

RECRUITING

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

RECRUITING

National Center for Child Health and Development

Tokyo, 113-8519, Japan

ACTIVE NOT RECRUITING

Erasmus MC

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

Universitair Medisch Centrum Utrecht - PPDS

Utrecht, 3584 CX, Netherlands

ACTIVE NOT RECRUITING

King Faisal Specialist Hospital & Research Center - Riyadh

Riyadh, Ar Riya, 11211, Saudi Arabia

ACTIVE NOT RECRUITING

King Fahad Medical City

Riyadh, Ar Riya, 11564, Saudi Arabia

NOT YET RECRUITING

King Abdullah Children's Specialist Hospital

Riyadh, Ar Riya, 14611, Saudi Arabia

NOT YET RECRUITING

Hospital Sant Joan de Deu - PIN

Esplugues de Llobregat, Barcelona, 8950, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Cruces

Barakaldo, Biscay, 48903, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario Virgen del Rocio - PPDS

Seville, 41013, Spain

ACTIVE NOT RECRUITING

University Hospital Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

RECRUITING

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

COMPLETED

Great Ormond Street Hospital for Children NHS Foundation Trust

London, WC1N 3JH, United Kingdom

RECRUITING

Willink Biochemical Genetics Unit - PPDS

Manchester, M13 9WL, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 36577040 DERIVED

MeSH Terms

Conditions

Propionic Acidemia; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Amino Acid Metabolism, Inborn Errors; Acidosis; Acid-Base Imbalance; Metabolic Diseases

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases

Central Study Contacts

Moderna WeCare Team

CONTACT

1-866-663-3762; WeCareClinicalTrials@modernatx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 12, 2019
• Study Start: April 15, 2021
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3); CA (2); US (15); FR (2); GB (4); SA (3); NL (2); ES (4)