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

Description

This First-in-Human (FIH) Phase 1/2 study is designed to characterize the safety, tolerability, and pharmacological activity (as assessed by biomarker measurements) and to determine the optimal dose of mRNA-3927 in participants with genetically confirmed propionic acidemia (PA). After establishing a dose with acceptable safety and pharmacodynamic (PD) response in a Dose Optimization Group (Part 1) in participants ≥1 year of age, additional participants will be enrolled into the study in a Dose Expansion Group (Part 2) to allow for further characterization 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

Study Overview

Study Details

Study overview

This First-in-Human (FIH) Phase 1/2 study is designed to characterize the safety, tolerability, and pharmacological activity (as assessed by biomarker measurements) and to determine the optimal dose of mRNA-3927 in participants with genetically confirmed propionic acidemia (PA). After establishing a dose with acceptable safety and pharmacodynamic (PD) response in a Dose Optimization Group (Part 1) in participants ≥1 year of age, additional participants will be enrolled into the study in a Dose Expansion Group (Part 2) to allow for further characterization 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).

A Global, Phase 1/2, Open-Label, Dose Optimization Study to Evaluate the Safety, Pharmacodynamics, and Pharmacokinetics of mRNA-3927 in Participants With Propionic Acidemia

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

Condition
Propionic Acidemia
Intervention / Treatment

-

Contacts and Locations

Los Angeles

Ronald Reagan UCLA Medical Center, Los Angeles, California, United States, 90095

Stanford

Lucile Packard Children's Hospital Stanford, Stanford, California, United States, 94304

Baltimore

Johns Hopkins Hospital, Adult Outpatient Clinical Research Unit, Baltimore, Maryland, United States, 21287

Boston

Boston Children's Hospital, Boston, Massachusetts, United States, 02115

Ann Arbor

University of Michigan Hospitals, Ann Arbor, Michigan, United States, 48109

New York

Icahn School of Medicine at Mount Sinai - Clinical Research Unit, New York, New York, United States, 10029

Durham

Duke University Medical System (Duke Health), Durham, North Carolina, United States, 27710

Cincinnati

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States, 45229

Philadelphia

Children's Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, United States, 19104

Houston

Texas Children's Hospital, Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * ≥ 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.
  • * Confirmed diagnosis of PA based on diagnosis by molecular genetic testing (PCCA and/or PCCB mutations).
  • * Part 2 only: At least one documented MDE in the 12-month period before consent.
  • * 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.
  • * ≥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 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 (eg, 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 (decreased pH) with high anion gap, or compensated metabolic acidosis (reduced bicarbonate, or base deficit, or reduced PaCO2 or increased lactate) with high anion gap.
  • * Acute hyperammonemia.
  • * Neutropenia or thrombocytopenia.
  • * Any individual with laboratory abnormalities achieving theresholds defined in the protocol
  • * 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.

Ages Eligible for Study

to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

ModernaTX, Inc.,

Study Record Dates

2027-01-06