AAVrh10-PCCA Gene Therapy for Propionic Acidemia

ConditionPropionic Acidemia

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age6-2

SponsorMayo Clinic

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

Hemoglobin <10 g/dl

Platelet count < 100,000 per mm3

Liver Enzyme ALT/AST >2.5 ULN

Direct Bilirubin > 1.5

Trial design

Design model

Sequential

Treatments tested in this trial

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.
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.
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.

Treatment groups

9 Participants

are divided into 3 treatment groups

Group A: Gene Therapy First Cohort (3 patients)Experimental treatment 1 intervention

Group B: Gene Therapy Second Cohort (3 patients)Experimental treatment 1 intervention

Group C: Gene Therapy Third Cohort (3 patients)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

7 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

Source ClinicalTrials.gov

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