AAVrh10-PCCA Gene Therapy for Propionic Acidemia
Purpose
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.
Condition
- Propionic Acidemia
Eligibility
- Eligible Ages
- Between 6 Months and 2 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Each group will receive AAVrh10-PCCA. The first cohort will receive the low dose, the second cohort the medium dose, and the third cohort the high dose.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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 |
|
Recruiting Locations
Mayo Clinic
Rochester, Minnesota 55905
Rochester, Minnesota 55905
More Details
- Status
- Recruiting
- Sponsor
- Mayo Clinic