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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05345171
Other study ID # DTX301-CL301
Secondary ID 2020-003384-25
Status Recruiting
Phase Phase 3
First received
Last updated
Start date October 18, 2022
Est. completion date December 2028

Study information

Verified date June 2024
Source Ultragenyx Pharmaceutical Inc
Contact Patients Contact: Trial Recruitment
Phone 1-888-756-8657
Email TrialRecruitment@ultragenyx.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 with removal of dietary protein restriction and alternative pathway medication.


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 group and followed closely for 64 weeks. At week 64 eligible patients will crossover and receive DTX301 if they had previously received placebo or placebo if they had previously received DTX301. 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.


Recruitment information / eligibility

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

Study Design


Related Conditions & MeSH terms


Intervention

Genetic:
DTX301
non-replicating, self-complementary recombinant adeno-associated virus serotype 8 (AAV8) vector
Other:
Placebo
normal saline infusion
Drug:
Oral Corticosteroids
Participants who receive DTX301 solution will receive oral corticosteroids.
Placebo for oral corticosteroids
Participants who receive Placebo will receive placebo corticosteroids to maintain the study blind
Sodium Acetate
A tracer for the Ureagenesis Rate Test (URT)

Locations

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

Sponsors (1)

Lead Sponsor Collaborator
Ultragenyx Pharmaceutical Inc

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  France,  Germany,  Italy,  Japan,  Netherlands,  Portugal,  Spain,  United Kingdom, 

Outcome

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
See also
  Status Clinical Trial Phase
Recruiting NCT05526066 - Study for Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency to Evaluate Safety and Tolerability of ARCT-810 Phase 2
Completed NCT04248062 - Patient and Observer Reported Outcome Measurements in Inborn Errors of Metabolism