Study to Characterize Rate of Ureagenesis in Patients With Ornithine Transcarbamylase (OTC) Deficiency

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Ornithine Transcarbamylase Deficiency

Intervention / Treatment
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* Other: No Intervention


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult Patients with OTC Deficiency<br>Eligible subjects will be asked to participate in 5 clinic visits, each lasting up to 3 days. Each visit will assess rate of ureagenesis during the 4 hours following ingestion of [1-13C]sodium acetate. Sodium acetate is used as a tracer to measure the rate of ureagenesis. Patient interview, reported outcomes and cognitive assessments will take place over the 3 days. | Other: No Intervention<br>* No Intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate over time of ureagenesis for 4 hours based on presence of [1-13C] in urea | Urea excretion after ingestion of sodium acetate as measured in blood | Predose (0hour) up to 4 hours post dose at Baseline, Weeks 24, 48, 72, and 96 | 
| OTC Genotype | Genotype in blood | Up to 96 weeks | 
| Rate of Hyperammonemic Crisis (HAC) |  | Up to 96 weeks | 
| Cognitive assessment | Cogstate platform | Up to 96 weeks | 
| Hyperammonemia Indicator Questionnaire (HI-Q) | Patient-reported outcome (PRO) for symptoms of hyperammonemia | Up to 96 weeks | 
| OTC Deficiency Impact Questionnaire (OTC-D-IQ) | PRO for impact of hyperammonemia | Up to 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OTC, OTC Deficiency, Neonatal, Late Onset, Asymptomatic Carrier