[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07643844":3,"trial-entities:NCT07643844":100,"trial-summary:NCT07643844":104},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":10,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":14,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":19,"study_type":20,"primary_purpose":21,"phases":22,"enrollment_info":24,"interventions":27,"primary_outcomes":44,"secondary_outcomes":49,"sex":50,"minimum_age":51,"maximum_age":52,"healthy_volunteers":53,"eligibility_criteria":54,"std_ages":72,"locations":74,"central_contacts":88,"overall_officials":94,"references":98,"see_also_links":99},"NCT07643844","20-005247","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","RECRUITING","2033-12","2026-06","2026-06-23","Mayo Clinic","OTHER",true,"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.",null,[18],"Propionic Acidemia",[],"INTERVENTIONAL","TREATMENT",[23],"PHASE1",{"count":25,"type":26},9,"ESTIMATED",[28,34,39],{"type":29,"name":30,"description":31,"armGroupLabels":32},"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.",[33],"Gene Therapy First Cohort (3 patients)",{"type":29,"name":35,"description":36,"armGroupLabels":37},"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.",[38],"Gene Therapy Second Cohort (3 patients)",{"type":29,"name":40,"description":41,"armGroupLabels":42},"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.",[43],"Gene Therapy Third Cohort (3 patients)",[45],{"measure":46,"description":47,"timeFrame":48},"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",[],"ALL","6 Months","2 Years",false,{"inclusion":55,"exclusion":60,"raw_text":71},[56,57,58,59],"Age six months to 2 years of age at day of vector infusion. For those \\\u003C1 year of age they must have been ≥37 weeks gestational age at the time of birth and without other conditions\u002Fcomorbidities 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.",[61,62,63,64,65,66,67,68,69,70],"Hemoglobin \\\u003C10 g\u002Fdl","Platelet count \\\u003C 100,000 per mm3","Liver Enzyme ALT\u002FAST \\>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 \\\u003C 7.3, bicarbonate \\\u003C 15 mmol\u002FL, NH3 \\> 75 mcmol\u002FL, lactate \\> 2.5 mmol\u002FL, 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.","Inclusion Criteria:\n\n* Age six months to 2 years of age at day of vector infusion. For those \\\u003C1 year of age they must have been ≥37 weeks gestational age at the time of birth and without other conditions\u002Fcomorbidities that in the opinion of the Investigator may interfere with the interpretation of study results.\n* Confirmed diagnosis of propionic acidemia with biallelic PCCA gene mutations based on molecular genetic testing.\n* 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.\n* 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.\n\nExclusion Criteria:\n\n* Hemoglobin \\\u003C10 g\u002Fdl\n* Platelet count \\\u003C 100,000 per mm3\n* Liver Enzyme ALT\u002FAST \\>2.5 ULN\n* Direct Bilirubin \\> 1.5\n* Active viral infection (includes HIV or serology positive for hepatitis B or C).\n* Previous liver transplant\n* Subjects with active decompensation as demonstrated by a pH \\\u003C 7.3, bicarbonate \\\u003C 15 mmol\u002FL, NH3 \\> 75 mcmol\u002FL, lactate \\> 2.5 mmol\u002FL, urine ketones\n* Previously received gene therapy or messenger ribonucleic acid (mRNA) treatments for PA.\n* Grade 3 or 4 heart failure according to the Modified Ross Heart Failure Classification for Children or the New York Heart Association Classification.\n* Family does not want to disclose patient's study participation with primary care physician and other medical providers.",[73],"CHILD",[75],{"facility":12,"status":8,"city":76,"state":77,"zip":78,"country":79,"contacts":80,"geoPoint":85},"Rochester","Minnesota","55905","United States",[81],{"name":82,"role":83,"email":84},"Clinical Genomics Clinical Research Team","CONTACT","rstcgresearch@mayo.edu",{"lat":86,"lon":87},44.02163,-92.4699,[89,91],{"name":82,"role":83,"phone":90,"email":84},"507-538-6151",{"name":92,"role":83,"email":93},"Wyatt Anians, M.S., CCRP","anians.wyatt@mayo.edu",[95],{"name":96,"affiliation":12,"role":97},"David R. Deyle, MD","PRINCIPAL_INVESTIGATOR",[],[],{"nct_id":4,"conditions":101,"biomarkers":102},[18],[103],"PROPIONYL-CoA CARBOXYLASE, ALPHA SUBUNIT",{"nct_id":4,"found":53,"summary":16,"prompt_version":16}]