AAVrh10-PCCA Gene Therapy for Propionic Acidemia

NCT07643844 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-005247
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Gene Therapy First Cohort (3 patients)

EXPERIMENTAL

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

Gene Therapy Second Cohort (3 patients)

EXPERIMENTAL

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

Gene Therapy Third Cohort (3 patients)

EXPERIMENTAL

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

Interventions

AAVrh10-PCCA low dose DRUG

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.

Gene Therapy First Cohort (3 patients)

AAVrh10-PCCA middle dose DRUG

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.

Gene Therapy Second Cohort (3 patients)

AAVrh10-PCCA high dose DRUG

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.

Gene Therapy Third Cohort (3 patients)

Eligibility Criteria

• Age: 6 Months - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Propionic Acidemia

Condition Hierarchy (Ancestors)

Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• David R. Deyle, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Genomics Clinical Research Team

CONTACT

507-538-6151; rstcgresearch@mayo.edu

Wyatt Aians, M.S., CCRP

CONTACT

anians.wyatt@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 12, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2033
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)