Clinical trial • Phase I/II • Rare Disease|Endocrinology

modified messenger ribonucleic acid encoding human propionyl-coenzyme a carboxylase alpha and beta subunits encapsulated into lipid nanoparticles for Propionic acidemia

Phase I/II trial of modified messenger ribonucleic acid encoding human propionyl-coenzyme a carboxylase alpha and beta subunits encapsulated into lipid na…

Overview

Trial Therapeutic Area
Rare Disease|Endocrinology
Trial Disease
Propionic acidemia
Trial Stage
Phase I/II
Drug Modality
mRNA
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
21-10-2025
First CTIS Authorization Date
23-02-2026

Trial design

open-label Phase I/II trial in France, Spain, Netherlands.

Open Label
Yes
Target Sample Size
25

Eligibility

Recruits 25 paediatric patients.

Pregnancy Exclusion
Pregnant or breastfeeding.
Vulnerable Population
Participants include children/paediatric patients; consent/assent is handled per local regulations. The protocol requires that the participant and/or legally authorized representative provide informed consent and/or assent. A participant’s caregiver (and, if able to provide consent/assent, the participant) must be willing and able to comply with study assessments. Age-specific assent/consent documents are provided (assent ICFs for ages 06 to 10, 11 to 14, 15 to 17; parent/parental ICFs; adult ICFs) as indicated in country-specific documents.

Inclusion criteria

  • {"criterion_text":"- Participated in Study mRNA-3927-P101.\n- Completed the EOT/ ET Visit in Study mRNA-3927-P101 and enroll in this study such that the first dose in this study is planned to be within 14±3 days of the last dose of mRNA-3927 in mRNA-3927-P101 study.\n- Participant and/or legally authorized representative is willing and able to provide informed consent and/or assent as mandated by local regulations.\n- Participant’s caregiver (and, if able to provide consent/assent, the participant) is willing and able to comply with study-related assessments."}

Exclusion criteria

  • {"criterion_text":"- Not expected to receive clinical benefit from continued mRNA-3927 administration, in the opinion of the Investigator.\n- Any clinical or laboratory abnormality or medical condition that, at the discretion of the Investigator, may put the individual at increased risk by participating in this study.\n- History of liver and/or kidney transplant.\n- Pregnant or breastfeeding.\n- Sexually active and does not agree to use a highly effective method of contraception during the Treatment Period and for 3 months after the last dose of the mRNA-3927."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Incidence and severity of AEs (including mRNA-3927 -related and not related AEs), SAEs, and AEs leading to treatment discontinuation.","definition_or_measurement_approach":"Measured by investigator-reported adverse events and serious adverse events; safety monitoring throughout the study includes vital signs, physical examinations, clinical laboratory analyses, ADAs, 12-lead ECGs, and reporting of AEs and SAEs."}

Secondary endpoints

  • {"endpoint_text":"- Annualized frequency of Investigator-reported MDEs.","definition_or_measurement_approach":"Annualized frequency based on investigator-reported major disease events (MDEs)."}
  • {"endpoint_text":"- Annualized frequency of Investigator-reported MDE-related hospitalizations.","definition_or_measurement_approach":"Annualized frequency based on investigator-reported hospitalizations related to MDEs."}
  • {"endpoint_text":"- Annualized frequency of Investigator-reported PA-related hospitalizations.","definition_or_measurement_approach":"Annualized frequency based on investigator-reported hospitalizations related to propionic acidemia (PA)."}
  • {"endpoint_text":"- Annualized frequency of Investigator-reported PA-related urgent healthcare encounters.","definition_or_measurement_approach":"Annualized frequency based on investigator-reported PA-related urgent healthcare encounters."}

Recruitment

Planned Sample Size
25
Recruitment Window Months
115
Consent Approach
Informed consent is provided by the participant and/or legally authorized representative as required by local regulations. Assent is required where appropriate; caregiver involvement is required and caregiver (and participant if able) must agree to comply with study assessments. Age-specific assent/consent documents are available (assent ICFs for ages 06 to 10, 11 to 14, 15 to 17; consent for 12-17 in some country documents; adult ICFs; parent/parental ICFs). Country-specific documents are provided (examples in French, Spanish, and Dutch as listed in trial documents).

Methods

  • Recruitment of participants previously enrolled in Study mRNA-3927-P101 (site-based recruitment at participating hospitals).
  • Use of site-provided participant materials and support (Clincierge travel support, participant welcome letters, patient educational toolkits) to facilitate participation and travel reimbursement.

Geography

Total Number Of Sites
6
Total Number Of Participants
13

France

Earliest CTIS Part Ii Submission Date
07-11-2025
Latest Decision Or Authorization Date
23-02-2026
Processing Time Days
108
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Assistance Publique Hopitaux De Paris
Department Name
CIC 1419 Service Maladies Métaboliques Pédiatriques
Contact Person Name
Manuel Schiff
Contact Person Email
manuel.schiff@aphp.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Service Neurometabolisme pédiatrique
Contact Person Name
Célia Hoebeke
Contact Person Email
Celia.hoebeke@ap-hm.fr

Spain

Earliest CTIS Part Ii Submission Date
05-12-2025
Latest Decision Or Authorization Date
24-02-2026
Processing Time Days
81
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Hospital Universitario De Cruces
Department Name
Servicio de Pediatría. Sección de Enfermedades Metabólicas Hereditarias
Contact Person Name
Javier Adolfo de las Heras
Site Name
Hospital Universitario 12 De Octubre
Department Name
Servicio de Pediatría. Unidad de Enfermedades Metabólicas
Contact Person Name
Marcello Bellusci

Netherlands

Earliest CTIS Part Ii Submission Date
20-02-2026
Latest Decision Or Authorization Date
27-02-2026
Processing Time Days
7
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Universitair Medisch Centrum Utrecht
Department Name
Metabolic diseases
Contact Person Name
Peter Van Hasselt
Contact Person Email
P.vanHasselt@umcutrecht.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Internal medicine
Contact Person Name
Margreet Wagenmakers
Contact Person Email
m.wagenmakers@erasmusmc.nl

Sponsor

Primary sponsor

Full Name
Moderna Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Ppd Inc.
Responsibilities
Bioanalytical laboratory analisys
Name
Pharmaceutical Product Development LLC
Responsibilities
Central Lab, Laboratory sample management, bioanalytical analysis; Pharmacovigilance (for other entries)
Name
PPD Development LP
Responsibilities
Bioanalytical laboratory analysis
Name
PPD Development Ireland Limited
Responsibilities
distribution of non-IP ancillary supplies
Name
PPD Global Central Labs
Responsibilities
Biomarker sample long term storage

Third parties

  • {"country":"United States","full_name":"Charles River Laboratories International Inc.","duties_or_roles":"Bioanalytical laboratory analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"IP Depot and QP ( packaging/labelling, distribution (including QP and depot setup), returns/reconciliation)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"Bioanalytical laboratory analisys","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Central Lab, Laboratory sample management, bioanalytical analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Bioanalytical laboratory analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Pharmacovigilance","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Biomarker sample long term storage","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"IP Depot and QP ( packaging/labelling, distribution (including QP and depot setup), returns/reconciliation)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Praxis Communications LLC","duties_or_roles":"provides trial educational toolkits for both sites and patients","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"Patient travel, logistic and reimbursement","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"PPD Development Ireland Limited","duties_or_roles":"distribution of non-IP ancillary supplies","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
mRNA-3927
Active Substance
modified messenger ribonucleic acid encoding human propionyl-coenzyme a carboxylase alpha and beta subunits encapsulated into lipid nanoparticles
Modality
mRNA
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Authorisation Status
1
Orphan Designation
Yes

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