Sponsor's Decision

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.

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.

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

Approximately 30 patients will be enrolled, with up to 6 (20%) asymptomatic patients and at least 18 (60%) patients with late-onset OTC deficiency.