The primary objective is to evaluate the efficacy of DTX301 on the improvement of ornithine transcarbamylase (OTC) function by maintaining safe plasma ammonia levels.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
32
University of California
Los Angeles, California, United States
University of Colorado
Aurora, Colorado, United States
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
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)
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Participants who receive Placebo will receive placebo corticosteroids to maintain the study blind
A tracer for the Ureagenesis Rate Test (URT)
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Hospital Italiano de Buenos Aires
Buenos Aires, Argentina
Clinica Universitaria Reina Fabiola
Córdoba, Argentina
Hospital de Clinicas de Porto Alegre
Porto Alegre, Brazil
The Hospital for Sick Children
Toronto, Ontario, Canada
Hopital Femme Mere Enfant
Bron, France
Necker-Enfants Maladas Hospital
Paris, France
...and 6 more locations
Time frame: Up to Week 324
Number of Participants With Anti-OTC Antibodies
Time frame: 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
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