AAVrh10-PCCA Gene Therapy for Propionic Acidemia
ConditionPropionic Acidemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age6-2
SponsorMayo Clinic
About this trial
Propionic acidemia is a genetic metabolic disorder characterized by metabolic acidosis, ketosis, vomiting, lethargy, cognitive impairment, and risk of death. It results from loss of function of the mitochondrial enzyme propionyl-CoA carboxylase and can be due to disease-causing variants in the PCCA gene, leading to accumulation of propionyl-CoA and its toxic metabolites. The purpose of this trial is to evaluate the safety and potential therapeutic benefit of an AAV-based gene therapy for propionic acidemia in patients with genetically confirmed biallelic variants in PCCA.
Eligibility criteria
Qualifiers
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.
Disqualifiers
Hemoglobin <10 g/dl
Platelet count < 100,000 per mm3
Liver Enzyme ALT/AST >2.5 ULN
Direct Bilirubin > 1.5
Trial design
Treatments tested in this trial
- AAVrh10-PCCA low dose
- AAVrh10-PCCA middle dose
- AAVrh10-PCCA high dose
Treatment groups
9 Participants
are divided into 3 treatment groupsSponsors and collaborators
Source ClinicalTrials.gov