Recruiting
Phase 1

AAV Gene Therapy

Sponsor:

Mayo Clinic

Code:

NCT07643844

Conditions

Propionic Acidemia

Eligibility Criteria

Sex: All

Age: 0 - 2

Healthy Volunteers: Not accepted

Interventions

AAVrh10-PCCA low dose

AAVrh10-PCCA middle dose

AAVrh10-PCCA high dose

Study Details

Brief 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.

Conditions

Propionic Acidemia

Study ID

NCT07643844

Start date

Jul 20, 2026

Status verified date

Aug, 2026

Completion date

Dec, 2033

Anticipated

Primary completion date

Dec, 2032

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 2

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

9 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Gene Therapy First Cohort (3 patients)

AAVrh10-PCCA, single dose of 2 x 10\^12 vg per kilogram of body weight (first three patients), IV administration

experimental: Gene Therapy Second Cohort (3 patients)

AAVrh10-PCCA, single dose of 8 x 10\^12 vg per kilogram of body weight (middle three patients), IV administration

experimental: Gene Therapy Third Cohort (3 patients)

AAVrh10-PCCA, single dose of 3.2 x 10\^13 vg per kilogram of body weight (last three patients), IV administration

Interventions

AAVrh10-PCCA low dose

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 middle dose

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 high dose

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.

Primary outcome measure

  • Incidence of treatment-emergent adverse events [ Time Frame: 7 years ]

Central Contacts and Locations

Central contacts

Clinical Genomics Clinical Research Team

507-538-6151rstcgresearch@mayo.edu

Wyatt Anians, M.S., CCRP

anians.wyatt@mayo.edu

Locations

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Genomics Clinical Research Team

rstcgresearch@mayo.edu

More Information

Sponsor

Mayo Clinic

Last update posted

Aug 21, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-08-21.