AAV-based gene therapy for Propionic Acidemia in young children

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

Propionic Acidemia is caused by variants in the PCCA gene leading to a buildup of toxic metabolites. This Phase 1 study uses an adeno-associated virus vector to deliver a functional PCCA gene at low, middle, and high doses in eligible infants and toddlers. The aim is to evaluate safety and potential early signs of therapeutic benefit in genetically confirmed cases with a history of metabolic decompensation. Participants must be between six months and two years old at infusion, with neonatal-onset disease and prior decompensation events. The study is led by Mayo Clinic and conducted at a Mayo Clinic site in Rochester, Minnesota.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Age six months to 2 years of age at day of vector infusion. For those \<1 year of age they must have been ≥37 weeks gestational age at the time of birth and without other conditions/comorbidities that in the opinion of the Investigator may interfere with the interpretation of study results.
* Confirmed diagnosis of propionic acidemia with biallelic PCCA gene mutations based on molecular genetic testing.
* Study participants must have a diagnosis of neonatal-onset propionic acidemia with a documented episode of decompensation that can include any of the following findings: lethargy, poor feeding, irritability, vomiting, encephalopathy, respiratory failure, seizures, coma, metabolic acidosis, lactic acidosis, ketonuria, hypoglycemia, hyperammonemia, and cytopenias or history of recurrent hospitalizations.
* Parents or legal guardians of study participants must agree to comply in good faith with the conditions of the study, including attending all of the required baseline and follow-up assessments, and parents or legal guardians must give consent for their child's participation.

Exclusion Criteria:

* Hemoglobin \<10 g/dl
* Platelet count \< 100,000 per mm3
* Liver Enzyme ALT/AST \>2.5 ULN
* Direct Bilirubin \> 1.5
* Active viral infection (includes HIV or serology positive for hepatitis B or C).
* Previous liver transplant
* Subjects with active decompensation as demonstrated by a pH \< 7.3, bicarbonate \< 15 mmol/L, NH3 \> 75 mcmol/L, lactate \> 2.5 mmol/L, urine ketones
* Previously received gene therapy or messenger ribonucleic acid (mRNA) treatments for PA.
* Grade 3 or 4 heart failure according to the Modified Ross Heart Failure Classification for Children or the New York Heart Association Classification.
* Family does not want to disclose patient's study participation with primary care physician and other medical providers.

Where it's running

• Mayo Clinic
  Rochester, Minnesota, United States Recruiting

Study contacts

• Principal investigator: David R. Deyle, MD — Mayo Clinic
• Study coordinator: Clinical Genomics Clinical Research Team
• Email: rstcgresearch@mayo.edu
• Phone: 507-538-6151

Similar studies

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

• 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

• Treatment for Propionic Acidemia using mRNA-3927

  This study is testing a new treatment called mRNA-3927 to see if it is safe and effective for people with propionic acidemia, including infants and older children.

  Recruiting at 19 sites Phase 1/2 ModernaTX, Inc. · Los Angeles, California and 34 other locations · NCT04159103

• 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.