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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Propionic Acidemia
• Intervention / Treatment: Drug: AAVrh10-PCCA low dose; Drug: AAVrh10-PCCA middle dose; Drug: AAVrh10-PCCA high dose

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Genomics Clinical Research Team; Phone Number: 507-538-6151; Email: rstcgresearch@mayo.edu
• Study Contact Backup: Name: Wyatt Aians, M.S., CCRP; Email: anians.wyatt@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: 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.
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	Drug: 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.
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	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events	Total number of treatment-emergency adverse events. Adverse events include serious adverse events, lab safety tests, vital signs, and dose-limiting toxicities.	7 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: David R. Deyle, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2033

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Amino Acid Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Propionic Acidemia
• Other Study ID Numbers: 20-005247

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No