Treatment for Propionic Acidemia using mRNA-3927

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This open-label study aims to evaluate the safety, tolerability, and pharmacological activity of mRNA-3927 in participants with genetically confirmed propionic acidemia. The study is divided into three parts: the first part focuses on dose optimization for participants aged one year and older, while the second part expands the participant group to further assess efficacy and safety. The third part specifically evaluates the treatment in infants under one year of age. Participants will undergo a predosing observational period, followed by treatment and a follow-up phase.

Why it matters

Who can join: the full rules

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.

Where it's running

• Ronald Reagan UCLA Medical Center
  Los Angeles, California, United States Recruiting
• Lucile Packard Children's Hospital Stanford
  Stanford, California, United States Recruiting
• Ann and Robert H Lurie Childrens Hospital of Chicago
  Chicago, Illinois, United States Recruiting
• University of Michigan Hospitals
  Ann Arbor, Michigan, United States Recruiting
• Icahn School of Medicine at Mount Sinai - Clinical Research Unit
  New York, New York, United States Recruiting
• Duke University Medical System (Duke Health)
  Durham, North Carolina, United States Recruiting

Study contacts

• Study coordinator: Moderna WeCare Team
• Email: WeCareClinicalTrials@modernatx.com
• Phone: 1-866-663-3762

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• AAV-based gene therapy for Propionic Acidemia in young children

  This trial tests whether an AAVrh10-PCCA gene therapy can be given safely to children with Propionic Acidemia to help their bodies manage the metabolic problem.

  Recruiting Phase 1 Mayo Clinic · Rochester, Minnesota · NCT07643844

• Characterizing people with propionic acidemia using past medical records

  This project collects and reviews medical records to see what health events and outcomes people with propionic acidemia experience.

  Recruiting at 15 sites ModernaTX, Inc. · Stanford, California and 28 other locations · NCT05769621

• Long-term safety assessment of mRNA-3927 for propionic acidemia patients

  This study is testing the long-term safety and effectiveness of the mRNA-3927 treatment for people with propionic acidemia who have already participated in a previous study.

  Recruiting at 12 sites Phase 1/2 ModernaTX, Inc. · Los Angeles, California and 21 other locations · NCT05130437

• Observing the effects of Carbaglu® in treating MMA and PA in patients

  This study is testing how safe Carbaglu® is for treating high ammonia levels in people with Methylmalonic Acidemia and Propionic Acidemia, both kids and adults.

  Recruiting at 5 sites Recordati Group · Washington D.C., District of Columbia and 4 other locations · NCT05040178

• Long-term management of organic acidemia with CARBAGLU®

  This study looks at how well carglumic acid helps people with propionic acidemia and methylmalonic acidemia over a long time, while also talking to patients and caregivers about their experiences.

  Recruiting at 31 sites Recordati Group · Bordeaux and 31 other locations · NCT04176523

• Understanding Propionic Acidemia and Its Effects

  This study is trying to learn more about propionic acidemia by looking at how it affects people with the condition and their families over time.

  Recruiting at 2 sites National Institutes of Health Clinical Center (CC) · Bethesda, Maryland and 1 other locations · NCT02890342

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.