OTC Deficiency Clinical Trial
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 with removal of dietary protein restriction and alternative pathway medication.
Status | Recruiting |
Enrollment | 50 |
Est. completion date | December 2028 |
Est. primary completion date | December 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 12 Years and older |
Eligibility | Key Inclusion Criteria: - 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 Week 128, 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: - 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 |
Country | Name | City | State |
---|---|---|---|
Argentina | Hospital Italiano de Buenos Aires | Buenos Aires | |
Argentina | Clinica Universitaria Reina Fabiola | Córdoba | |
Brazil | Hospital de Clinicas de Porto Alegre | Porto Alegre | |
Canada | The Hospital for Sick Children | Toronto | Ontario |
France | Hopital Femme Mere Enfant | Bron | |
France | Necker-Enfants Maladas Hospital | Paris | |
Germany | Universitatsklinikum Heidelberg | Heidelberg | |
Italy | University of Naples Federico II | Napoli | |
Italy | University Hospital of Padova | Padova | |
Italy | Ospedale Infantile Regina Margherita | Torino | |
Japan | Kumamoto University Hospital | Kumamoto | |
Japan | Fujita Health University Hospital | Toyoake | |
Netherlands | Erasmus Universitair Medisch Centrum Rotterrdam | Rotterdam | |
Portugal | Centro Hospitalar Universitario de Sao Joao | Porto | |
Spain | Fundacio Hospital Universitari Vall D'Hebron-Institute de Recerca | Barcelona | |
Spain | Hospital Clinico Universitario de Santiago | Santiago De Compostela | |
United Kingdom | University Hospitals Birmingham NHS | Birmingham | |
United States | University of Colorado | Aurora | Colorado |
United States | Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois |
United States | University Hospitals Cleveland Medical Center | Cleveland | Ohio |
United States | University of Florida College of Medicine | Gainesville | Florida |
United States | University of Arkansas for Medical Sciences | Little Rock | Arkansas |
United States | University of California | Los Angeles | California |
United States | Yale School of Medicine | New Haven | Connecticut |
United States | University of Utah | Salt Lake City | Utah |
Lead Sponsor | Collaborator |
---|---|
Ultragenyx Pharmaceutical Inc |
United States, Argentina, Brazil, Canada, France, Germany, Italy, Japan, Netherlands, Portugal, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Plasma Ammonia as Measured by 24-hour Ammonia (AUC0-24) | Week 64 | ||
Primary | Percentage of Participants Who Have Achieved Complete Response | Week 64 | ||
Secondary | Percentage of Participants Who Have Achieved Complete Response, Response, or No Response | Week 64 | ||
Secondary | Patient Global Impression of Change (PGIC) Overall Change Score | Week 64 | ||
Secondary | Rate of Hyperammonemic Crises (HACs) from Baseline to Week 64 Compared to Pre-Enrollment | Pre-enrollment, Baseline, Week 64 | ||
Secondary | Change from Baseline in Plasma Ammonia (AUC0-24) After DTX301 Exposure | Baseline, Up to Week 64 | ||
Secondary | Change from Baseline in Plasma Ammonia (AUC0-24) | Baseline, Up to Week 64 | ||
Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs, Related Serious TEAEs and Adverse Events of Special Interest (AESIs) | Up to Week 324 | ||
Secondary | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, Physical Examination Results, and Vital Sign Measurements | Baseline, Up to Week 324 | ||
Secondary | Number of Participants With Anti-OTC Antibodies | Up to Week 324 |
Status | Clinical Trial | Phase | |
---|---|---|---|
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