Ornithine Transcarbamylase Deficiency
Conditions
Keywords
OTC, OTC Deficiency, Neonatal, Late Onset, Asymptomatic Carrier
Brief summary
The objectives of the study are to characterize urea production rates in patients with OTC, characterize the association of rate of ureagenesis and disease severity in OTC patients, characterize the association of rate of ureagenesis and executive and verbal function and characterize the association of rate of ureagenesis and patient-reported functional status.
Detailed description
Study DTX301-CL102 is a noninterventional, observational study to characterize the rate of ureagenesis and to assess neurocognition and functional status in the spectrum of OTC deficiency and their association with biochemical characteristics. \[1-13C\]Sodium acetate will be administered orally as a tracer to measure the rate of ureagenesis.
Interventions
OTHERNo Intervention
No Intervention
Sponsors
Ultragenyx Pharmaceutical Inc
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Willing and able to provide written informed consent. * For symptomatic patients: * Confirmed clinical diagnosis of OTC deficiency and enzymatic, biochemical, or molecular testing. * Documented history of ≥ 1 symptomatic hyperammonemic episode with ammonia level ≥ 100 μmol/L * Patients on ongoing daily ammonia scavenger therapy must be at a stable dose(s) for ≥ 4 weeks prior to Visit 1 (Baseline) * For asymptomatic patients: confirmed diagnosis of OTC deficiency by family history and documented by molecular testing. * Willing and able to comply with the study procedures and requirements, including clinic visits, blood and urine collections, questionnaires, and cognitive assessments. Key
Exclusion criteria
* Liver transplant, including hepatocyte cell therapy/transplant. * History of liver disease * Significant hepatic inflammation or cirrhosis * Participation in another investigational medicine study within 3 months of Screening * Participation (current or previous) in another gene transfer study * Pregnant or nursing Other protocol specific criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate over time of ureagenesis for 4 hours based on presence of [1-13C] in urea | Predose (0hour) up to 4 hours post dose at Baseline, Weeks 24, 48, 72, and 96 | Urea excretion after ingestion of sodium acetate as measured in blood |
| OTC Genotype | Up to 96 weeks | Genotype in blood |
| Rate of Hyperammonemic Crisis (HAC) | Up to 96 weeks | — |
| Cognitive assessment | Up to 96 weeks | Cogstate platform |
| Hyperammonemia Indicator Questionnaire (HI-Q) | Up to 96 weeks | Patient-reported outcome (PRO) for symptoms of hyperammonemia |
| OTC Deficiency Impact Questionnaire (OTC-D-IQ) | Up to 96 weeks | PRO for impact of hyperammonemia |
Countries
United States
Outcome results
None listed