AAVrh10-PCCA Gene Therapy for Propionic Acidemia
Phase 1 Study of Intravenous Administration of a Serotype rh.10 Replication Deficient Adeno-associated Virus Gene Transfer Vector Expressing the Human Propionyl-CoA Carboxylase cDNA (AAVrh10-PCCA) to Individuals With Propionic Acidemia
Mayo Clinic
9 participants
Jun 1, 2026
INTERVENTIONAL
Conditions
Summary
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
Inclusion Criteria4
- 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 Criteria10
- 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.
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Interventions
AAVrh10-PCCA (Dose of 2 x 10\^12 vg per kg body weight) is an adeno-associated viral vector containing the adeno-associated virus terminal repeat sequences flanking a transgene cassette harboring the cytomegalovirus (CMV) immediate-early enhancer and beta actin promoter, the human PCCA cDNA, and the bovine growth hormone polyadenylation sequence.
AAVrh10-PCCA (Dose of 8 x 10\^12 vg per kg body weight) is an adeno-associated viral vector containing the adeno-associated virus terminal repeat sequences flanking a transgene cassette harboring the cytomegalovirus (CMV) immediate-early enhancer and beta actin promoter, the human PCCA cDNA, and the bovine growth hormone polyadenylation sequence.
AAVrh10-PCCA (Dose of 3.2 x 10\^13 vg per kg body weight) is an adeno-associated viral vector containing the adeno-associated virus terminal repeat sequences flanking a transgene cassette harboring the cytomegalovirus (CMV) immediate-early enhancer and beta actin promoter, the human PCCA cDNA, and the bovine growth hormone polyadenylation sequence.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07643844