Clinical trial NCT04717453: Study to Characterize Rate of Ureagenesis in Patients With Ornithine Transcarbamylase (OTC) Deficiency
Official title: A Study to Characterize Rate of Ureagenesis Utilizing Oral [1-13C] Sodium Acetate in the Spectrum of Severity of Patients With Ornithine Transcarbamylase (OTC) Deficiency
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Ornithine Transcarbamylase Deficiency
Keywords: OTC
OTC Deficiency
Neonatal
Late Onset
Asymptomatic Carrier
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
First posted: 2021-01-22
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Approximately 30 patients will be enrolled, with up to 6 (20%) asymptomatic patients and at least 18 (60%) patients with late-onset OTC deficiency.

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.

Eligibility 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

Primary outcomes:
measure: Rate over time of ureagenesis for 4 hours based on presence of [1-13C] in urea
timeFrame: Predose (0hour) up to 4 hours post dose at Baseline, Weeks 24, 48, 72, and 96
measure: OTC Genotype
timeFrame: Up to 96 weeks
measure: Rate of Hyperammonemic Crisis (HAC)
timeFrame: Up to 96 weeks
measure: Cognitive assessment
timeFrame: Up to 96 weeks
measure: Hyperammonemia Indicator Questionnaire (HI-Q)
timeFrame: Up to 96 weeks
measure: OTC Deficiency Impact Questionnaire (OTC-D-IQ)
timeFrame: Up to 96 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Orlando
country: United States
facility: PPD Phase 1 Clinic - Orlando
state: Florida
Study officials:
affiliation: Ultragenyx Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: