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

Study Purpose

This First-in-Human (FIH) Phase 1/2 study will evaluate mRNA-3927 in participants 1 year of age and older with propionic acidemia (PA). The study is designed to characterize baseline biomarker levels followed by assessment of safety, pharmacokinetics (PK), and pharmacodynamics (PD) of different doses of mRNA-3927 in participants affected by PA as part of the Dose Optimization phase.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 1 Year and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Participant must be ≥1 year of age at the time of consent/assent (Inclusion of the first 2 participants entering the study at the Dose Escalation stage will be restricted to individuals age ≥8 years) - Confirmed diagnosis of propionic acidemia based on diagnosis by molecular genetic testing (propionyl-CoA carboxylase subunit α [PCCA] and/or propionyl CoA carboxylase subunit β [PCCB] mutations)

    Exclusion Criteria:

    - Estimated glomerular filtration rate <30 milliliter (mL)/minute/1.73 m^2 as estimated by Schwartz formula; or participants who receive chronic dialysis.
  • - History of organ transplantation or planned organ transplantation during the period of study participation.
  • - QTc >480 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04159103
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

ModernaTX, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Canada, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Propionic Acidemia
Additional Details

During the Dose Optimization Stage, after each dose cohort is fully enrolled, and 21 days after the final participant in the cohort receives their first dose of study drug, 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 5 cohorts will be enrolled into the study. Upon establishment of a dose with acceptable safety and pharmacodynamic activity, additional participants will be enrolled in a Dose Expansion Stage to allow for further characterization of the safety and pharmacodynamics of mRNA-3927. Participants in both phases of study will participate in a predosing observational period, followed by a treatment period, and then a followup period after withdrawal of treatment.

Arms & Interventions

Arms

Experimental: Dose Optimization Stage: Dose Level 1

Participants will receive 1 dose of Dose Level 1 of mRNA-3927 by intravenous (IV) infusion on Day 1 of a 21-day period for up to 10 doses during the approximate 30-week Treatment Period.

Experimental: Dose Optimization Stage: Dose Level 2

Participants will receive 1 dose of Dose Level 2 of mRNA-3927 by IV infusion on Day 1 of a 21-day period for up to 10 doses during the approximate 30-week Treatment Period.

Experimental: Dose Optimization Stage: Dose Level 3

Participants will receive 1 dose of Dose Level 3 of mRNA-3927 by IV infusion on Day 1 of a 21-day period for up to 10 doses during the approximate 30-week Treatment Period.

Experimental: Dose Optimization Stage: Dose Level 4

Participants will receive 1 dose of Dose Level 4 of mRNA-3927 by IV infusion on Day 1 of a 21-day period for up to 10 doses during the approximate 30-week Treatment Period.

Experimental: Dose Optimization Stage: Dose Level 5

Participants will receive 1 dose of Dose Level 5 of mRNA-3927 by IV infusion on Day 1 of a 21-day period for up to 10 doses during the approximate 30-week Treatment Period.

Experimental: Dose Expansion Stage

Participant will receive the optimal dose of mRNA-3927 identified during the Dose Optimization Stage at 1 dose on Day 1 of each 21-day period for up to 10 doses during the approximate 30-week Treatment Period.

Interventions

Biological: - mRNA-3927

mRNA-3927 dispersion for IV infusion

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you. Please note all sites listed may not currently be active in the trial. Please continue to check back for additional site locations.

University of Michigan, Ann Arbor, Michigan

Status

Recruiting

Address

University of Michigan

Ann Arbor, Michigan, 48109

Duke University Medical Center, Durham, North Carolina

Status

Recruiting

Address

Duke University Medical Center

Durham, North Carolina, 27710

International Sites

Hospital For Sick Children, Toronto, Ontario, Canada

Status

Recruiting

Address

Hospital For Sick Children

Toronto, Ontario, M5G 1X8