OTC DeficiencyPhase 3NCT05345171
Clinical Study of DTX301 AAV-Mediated Gene Transfer for Ornithine Transcarbamylase (OTC) Deficiency
A Phase 3 study testing DTX301, Oral Corticosteroids and Sodium Acetate in people with OTC Deficiency, run by Ultragenyx Pharmaceutical Inc at 16 sites in 10 countries.
Trial summary
The primary objective is to evaluate the efficacy of DTX301 on the improvement of ornithine transcarbamylase (OTC) function by maintaining safe plasma ammonia levels. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- OTC Deficiency
- What is being tested?
- DTX301, Oral Corticosteroids and Sodium Acetate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 16 sitesin 10 countries
- Study dates
- 18 Oct 2022to Mar 2031
- Phase
- Phase 3
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Confirmed clinical diagnosis of late-onset OTC deficiency with historical documentation by enzymatic (ie, liver biopsy), biochemical (ie, hyperammonemia in the presence of elevated plasma glutamine, low citrulline, and elevated spot urine orotic acid), or molecular testing (ie, OTC analysis)
- Free from symptomatic hyperammonemia and has not required emergent active intervention for hyperammonemia within 4 weeks before screening/baseline
- If on ongoing daily ammonia scavenger therapy, must be at stable daily dose(s) for ≥ 4 weeks prior to screening
- If on a protein-restricted diet, must be on a stable total daily protein intake that does not vary more than 20% for ≥ 4 weeks prior to screening
- From the time written informed consent through Visit 28, females of childbearing potential and fertile males must consent to use highly effective contraception. If female, agree not to become pregnant. If male, agree not father a child or donate sperm
Who cannot join
- Significant hepatic inflammation or cirrhosis
- Estimated glomerular filtration rate < 60 mL/min/1.73 m2 at screening by the 2021 CKD-EPI creatinine-based formula (Inker et al., 2021) for patients ≥ 18 years of age or the Schwartz bedside formula (Schwartz and Work, 2009) for patients < 18 years of age
- Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, documented by current use of antiviral therapy for HBV or HCV or by hepatitis B surface antigen (HBsAg) or HCV RNA positivity
- Active infection (viral or bacterial)
- Detectable pre-existing antibodies to the AAV8 capsid
- Presence or history of any condition that, in the view of the Investigator, would interfere with participation, pose undue risk, or would confound interpretation of results
- Participation (current or previous) in another gene transfer study
- Note: Additional inclusion/exclusion criteria may apply, per protocol
Trial locations and contacts
16 sites in 10 countries.
16 sites in 10 countries
United States4 sites
University of Colorado
Aurora, Colorado, 80045
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
University of California
Los Angeles, California, 90095
Argentina2 sites
Hospital Italiano de Buenos Aires
Buenos Aires, C1199
Clinica Universitaria Reina Fabiola
Córdoba, X5004
France2 sites
Hopital Femme Mere Enfant
Bron, 69500
Necker-Enfants Maladas Hospital
Paris, 75015
Japan2 sites
Kumamoto University Hospital
Kumamoto, 860-8556
Fujita Health University Hospital
Toyoake, 470-1192
Netherlands1 site
Erasmus Universitair Medisch Centrum Rotterrdam
Rotterdam, 3015
Spain1 site
Fundacio Hospital Universitari Vall D'Hebron-Institute de Recerca
Barcelona, 08035
About this study
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Adeno-associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Patients With Late-onset OTC Deficiency
The primary objective is to evaluate the efficacy of DTX301 on the improvement of ornithine transcarbamylase (OTC) function by maintaining safe plasma ammonia levels.
Read the detailed description
This study is a Phase 3, randomized, double-blind, placebo-controlled study of DTX301 in patients with late-onset OTC deficiency 12 years of age and older.
Participants will be randomized 1:1 to DTX301 or placebo and followed closely for 36-64 weeks. Between Week 36 and Week 64, eligible participants will cross over and receive DTX301 if they had previously received placebo, and some who received DTX301 may receive placebo.
The planned study duration is up to 324 weeks. Upon completion of this study or early withdrawal, all participants who received DTX301 are invited to enroll in the Disease Monitoring Program (DMP) for follow-up for up to an additional 5 years.
- Conditions
- OTC Deficiency
- Being tested
- DTX301, Placebo, Oral Corticosteroids, Placebo for oral corticosteroids, Sodium Acetate
- Medical subject headings
- Ornithine Carbamoyltransferase Deficiency Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DTX301Genetic
Also called avalotcagene ontaparvovec
non-replicating, self-complementary recombinant adeno-associated virus serotype 8 (AAV8) vector
PlaceboOther
normal saline infusion
Oral CorticosteroidsDrug
Also called Prednisolone
Participants who receive DTX301 solution will receive oral corticosteroids.
Placebo for oral corticosteroidsDrug
Participants who receive Placebo will receive placebo corticosteroids to maintain the study blind
Sodium AcetateDrug
A tracer for the Ureagenesis Rate Test (URT)
| Study group | Role | What they receive |
|---|---|---|
| DTX301 | Experimental | Participants receive single peripheral intravenous (IV) infusion of DTX301 in solution. Between Week 36 and Week 64, participants may receive single peripheral IV infusion of placebo. Receives: Genetic: DTX301; Other: Placebo; Drug: Oral Corticosteroids; Drug: Placebo for oral corticosteroids; Drug: Sodium Acetate |
| Placebo, Then DTX301 | Experimental | Participants receive single peripheral IV infusion of placebo. Between Week 36 and Week 64, participants receive single peripheral IV infusion of DTX301 in solution. Receives: Genetic: DTX301; Other: Placebo; Drug: Oral Corticosteroids; Drug: Placebo for oral corticosteroids; Drug: Sodium Acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Ammonia as Measured by 24-Hour Ammonia (AUC0-24)
Measured: Week 36
Complete Responder Rate at the Final Study Visit After DTX301 Exposure
Measured: Up to 64 Weeks Post DTX301 Infusion
Secondary outcomes (11)
Percentage of Complete Responders or Responders After DTX301 Exposure
Measured: Up to 64 Weeks Post DTX301 Infusion
Annualized Event Rate of Hyperammonemic Crises (HACs) Pre-DTX301 Exposure vs Post-DTX301 Exposure
Measured: Pre-enrollment, Baseline, Up to 64 Weeks Post DTX301 Infusion
Annualized Event Rate of Interim Clinical Events (ICEs) Pre-DTX301 Exposure vs Post-DTX301 Exposure
Measured: Pre-enrollment, Baseline, Up to 64 Weeks Post DTX301 Infusion
Change from Baseline in Plasma Ammonia (AUC0-24)
Measured: Baseline, Up to Week 36
Change in Plasma Ammonia (AUC0-24) After DTX301 Exposure
Measured: Up to 64 Weeks Post DTX301 Infusion
Percentage of Participants Who Have Achieved Complete Management Response (CMR) or Management Response (MR) After DTX301 Exposure
Measured: Up to 64 Weeks Post DTX301 Infusion
Change in Baseline Disease Management (Dietary Protein and Total Scavenger Medication Use) With Plasma Ammonia (AUC0-24)
Measured: Up to 64 Weeks Post DTX301 Infusion
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs, Related Serious TEAEs and Adverse Events of Special Interest (AESIs)
Measured: Up to Week 324
Number of Participants With Anti-OTC Antibodies
Measured: Up to Week 324
Long-Term Durability of Response
Based Upon Number of Complete Responders or Responders That Have ≥ 2 Consecutive Visits as a Complete Responder or Responder and Do Not Return to a Lower Responder Status for > 1 Consecutive Visit
Measured: Up to 64 Weeks Post DTX301 Infusion
Change in Plasma Ammonia (AUC0-24) for Participants Who Have an Elevated Ammonia AUC0-24 at Baseline
Measured: Baseline, Up to 64 Weeks Post DTX301 Infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2022
- Study start18 Oct 2022
- Primary completionSep 2027 (estimated)
- Study completionMar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OTC DeficiencyStudies of the same condition, open and under way.
- More trials run by Ultragenyx Pharmaceutical IncThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05345171
- Sponsor's protocol ID
- DTX301-CL301
- Other IDs
- 2020-003384-25, 2024-514337-38-00
- Status last verified
- Sep 2026
- First submitted
- 18 Apr 2022
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Baruteau J, Brunetti-Pierri N, Gissen P. Liver-directed gene therapy for inherited metabolic diseases. J Inherit Metab Dis. 2024 Jan;47(1):9-21. doi: 10.1002/jimd.12709. Epub 2024 Jan 3.
PubMed 38171926
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Adeno-associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Patients With Late-onset OTC Deficiency
- ClinicalTrials.gov ID
- NCT05345171
- Acronym / sponsor ID
- DTX301-CL301
- Conditions
- OTC Deficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- 18 Oct 2022 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Mar 2031 (estimated)
- First posted
- 25 Apr 2022 (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.
The primary objective is to evaluate the efficacy of DTX301 on the improvement of ornithine transcarbamylase (OTC) function by maintaining safe plasma ammonia levels.
Detailed description
This study is a Phase 3, randomized, double-blind, placebo-controlled study of DTX301 in patients with late-onset OTC deficiency 12 years of age and older.
Participants will be randomized 1:1 to DTX301 or placebo and followed closely for 36-64 weeks. Between Week 36 and Week 64, eligible participants will cross over and receive DTX301 if they had previously received placebo, and some who received DTX301 may receive placebo.
The planned study duration is up to 324 weeks. Upon completion of this study or early withdrawal, all participants who received DTX301 are invited to enroll in the Disease Monitoring Program (DMP) for follow-up for up to an additional 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DTX301 | Experimental | Genetic: DTX301, Other: Placebo, Drug: Oral Corticosteroids, Drug: Placebo for oral corticosteroids, Drug: Sodium AcetateParticipants receive single peripheral intravenous (IV) infusion of DTX301 in solution. Between Week 36 and Week 64, participants may receive single peripheral IV infusion of placebo. |
| Placebo, Then DTX301 | Experimental | Genetic: DTX301, Other: Placebo, Drug: Oral Corticosteroids, Drug: Placebo for oral corticosteroids, Drug: Sodium AcetateParticipants receive single peripheral IV infusion of placebo. Between Week 36 and Week 64, participants receive single peripheral IV infusion of DTX301 in solution. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Confirmed clinical diagnosis of late-onset OTC deficiency with historical documentation by enzymatic (ie, liver biopsy), biochemical (ie, hyperammonemia in the presence of elevated plasma glutamine, low citrulline, and elevated spot urine orotic acid), or molecular testing (ie, OTC analysis)
- Free from symptomatic hyperammonemia and has not required emergent active intervention for hyperammonemia within 4 weeks before screening/baseline
- If on ongoing daily ammonia scavenger therapy, must be at stable daily dose(s) for ≥ 4 weeks prior to screening
- If on a protein-restricted diet, must be on a stable total daily protein intake that does not vary more than 20% for ≥ 4 weeks prior to screening
- From the time written informed consent through Visit 28, females of childbearing potential and fertile males must consent to use highly effective contraception. If female, agree not to become pregnant. If male, agree not father a child or donate sperm
Key exclusion criteria (8 listed)
- Significant hepatic inflammation or cirrhosis
- Estimated glomerular filtration rate < 60 mL/min/1.73 m2 at screening by the 2021 CKD-EPI creatinine-based formula (Inker et al., 2021) for patients ≥ 18 years of age or the Schwartz bedside formula (Schwartz and Work, 2009) for patients < 18 years of age
- Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, documented by current use of antiviral therapy for HBV or HCV or by hepatitis B surface antigen (HBsAg) or HCV RNA positivity
- Active infection (viral or bacterial)
- Detectable pre-existing antibodies to the AAV8 capsid
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 |
|---|---|---|
| DTX301Also: avalotcagene ontaparvovecnon-replicating, self-complementary recombinant adeno-associated virus serotype 8 (AAV8) vector | Genetic | DTX301, Placebo, Then DTX301 |
| Placebonormal saline infusion | Other | DTX301, Placebo, Then DTX301 |
| Oral CorticosteroidsAlso: PrednisoloneParticipants who receive DTX301 solution will receive oral corticosteroids. | Drug | DTX301, Placebo, Then DTX301 |
| Placebo for oral corticosteroidsParticipants who receive Placebo will receive placebo corticosteroids to maintain the study blind | Drug | DTX301, Placebo, Then DTX301 |
| Sodium AcetateA tracer for the Ureagenesis Rate Test (URT) | Drug | DTX301, Placebo, Then DTX301 |
Primary outcome
Plasma Ammonia as Measured by 24-Hour Ammonia (AUC0-24)
Time frame: Week 36
Complete Responder Rate at the Final Study Visit After DTX301 Exposure
Time frame: Up to 64 Weeks Post DTX301 Infusion
11 secondary outcomes
Percentage of Complete Responders or Responders After DTX301 Exposure
Time frame: Up to 64 Weeks Post DTX301 Infusion
Annualized Event Rate of Hyperammonemic Crises (HACs) Pre-DTX301 Exposure vs Post-DTX301 Exposure
Time frame: Pre-enrollment, Baseline, Up to 64 Weeks Post DTX301 Infusion
Annualized Event Rate of Interim Clinical Events (ICEs) Pre-DTX301 Exposure vs Post-DTX301 Exposure
Time frame: Pre-enrollment, Baseline, Up to 64 Weeks Post DTX301 Infusion
Change from Baseline in Plasma Ammonia (AUC0-24)
Time frame: Baseline, Up to Week 36
Change in Plasma Ammonia (AUC0-24) After DTX301 Exposure
Time frame: Up to 64 Weeks Post DTX301 Infusion
Percentage of Participants Who Have Achieved Complete Management Response (CMR) or Management Response (MR) After DTX301 Exposure
Time frame: Up to 64 Weeks Post DTX301 Infusion
Change in Baseline Disease Management (Dietary Protein and Total Scavenger Medication Use) With Plasma Ammonia (AUC0-24)
Time frame: Up to 64 Weeks Post DTX301 Infusion
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs, Related Serious TEAEs and Adverse Events of Special Interest (AESIs)
Time frame: Up to Week 324
Number of Participants With Anti-OTC Antibodies
Time frame: Up to Week 324
Long-Term Durability of Response
Time frame: Up to 64 Weeks Post DTX301 Infusion
Change in Plasma Ammonia (AUC0-24) for Participants Who Have an Elevated Ammonia AUC0-24 at Baseline
Time frame: Baseline, Up to 64 Weeks Post DTX301 Infusion
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 9 Sep 2026.
- Derived from this study: PubMed 38171926Baruteau J, Brunetti-Pierri N, Gissen P. Liver-directed gene therapy for inherited metabolic diseases. J Inherit Metab Dis. 2024 Jan;47(1):9-21. doi: 10.1002/jimd.12709. Epub 2024 Jan 3.
- Ultragenyx Patient Advocacy/OTC Disease InformationLink provided by the sponsor.
- Ultragenyx Transparency CommitmentLink provided by the sponsor.
- 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. This study is not recruiting at the moment.
Medical Director study director
Ultragenyx Pharmaceutical Inc
16 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing DTX301, Oral Corticosteroids and Sodium Acetate in people with OTC Deficiency, run by Ultragenyx Pharmaceutical Inc at 16 sites in 10 countries.
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 5 inclusion and 8 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: under way, not looking for participants, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Argentina, France, Japan, Brazil and 5 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Ammonia as Measured by 24-Hour Ammonia (AUC0-24) (time frame: Week 36). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05345171, which also lists 1 linked publication.
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 9 Sep 2026.