Propionic AcidemiaPhase 1NCT07643844
AAVrh10-PCCA Gene Therapy for Propionic Acidemia
A Phase 1 study testing AAVrh10-PCCA low dose, AAVrh10-PCCA middle dose and AAVrh10-PCCA high dose in people with Propionic Acidemia, run by Mayo Clinic at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 months to 2 years
- Conditions the study is for
- Propionic Acidemia
- What is being tested?
- AAVrh10-PCCA low dose, AAVrh10-PCCA middle dose and AAVrh10-PCCA high dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jul 2026to Dec 2033
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 2 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Wyatt Anians, M.S., CCRP contact
United States1 site, 1 recruiting
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Clinical Genomics Clinical Research Team, rstcgresearch@mayo.edu
About this study
Official title: 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.
- Conditions
- Propionic Acidemia
- Being tested
- AAVrh10-PCCA low dose, AAVrh10-PCCA middle dose, AAVrh10-PCCA high dose
- Medical subject headings
- Propionic Acidemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAVrh10-PCCA low doseDrug
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 doseDrug
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 doseDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: AAVrh10-PCCA high dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2026
- Study start20 Jul 2026
- Primary completionDec 2032 (estimated)
- Study completionDec 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Propionic AcidemiaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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.
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David R. Deyle, Mayo Clinic
- Investigators
- David R. Deyle, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07643844
- Sponsor's protocol ID
- 20-005247
- Status last verified
- Aug 2026
- First submitted
- 8 Jun 2026
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07643844
- Acronym / sponsor ID
- 20-005247
- Conditions
- Propionic Acidemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 20 Jul 2026 (actual)
- Primary completion
- Dec 2032 (estimated)
- Study completion
- Dec 2033 (estimated)
- First posted
- 12 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Gene Therapy First Cohort (3 patients) | Experimental | Drug: AAVrh10-PCCA low doseAAVrh10-PCCA, single dose of 2 x 10^12 vg per kilogram of body weight (first three patients), IV administration |
| Gene Therapy Second Cohort (3 patients) | Experimental | Drug: AAVrh10-PCCA middle doseAAVrh10-PCCA, single dose of 8 x 10^12 vg per kilogram of body weight (middle three patients), IV administration |
| Gene Therapy Third Cohort (3 patients) | Experimental | Drug: AAVrh10-PCCA high doseAAVrh10-PCCA, single dose of 3.2 x 10^13 vg per kilogram of body weight (last three patients), IV administration |
Who may qualify
- Ages
- 6 months to 2 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAVrh10-PCCA low doseAAVrh10-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. | Drug | Gene Therapy First Cohort (3 patients) |
| AAVrh10-PCCA middle doseAAVrh10-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. | Drug | Gene Therapy Second Cohort (3 patients) |
| AAVrh10-PCCA high doseAAVrh10-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. | Drug | Gene Therapy Third Cohort (3 patients) |
Primary outcome
Incidence of treatment-emergent adverse events
Time frame: 7 years
Total number of treatment-emergency adverse events. Adverse events include serious adverse events, lab safety tests, vital signs, and dose-limiting toxicities.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Wyatt Anians, M.S., CCRP contact
David R. Deyle, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AAVrh10-PCCA low dose, AAVrh10-PCCA middle dose and AAVrh10-PCCA high dose in people with Propionic Acidemia, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Genomics Clinical Research Team (507-538-6151, rstcgresearch@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-emergent adverse events (time frame: 7 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2026.