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

Terminated

• Conditions: Ornithine Transcarbamylase Deficiency
• Interventions: Other: No Intervention

• Registration Number: NCT04717453
• Lead Sponsor: Ultragenyx Pharmaceutical Inc

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.

Study Timeline

• Study Start: 2020-10-06
• Study First Submitted: 2021-01-15
• Study First Submitted QC: 2021-01-15
• Study First Posted: 2021-01-22
• Primary Completion: 2021-12-15
• Study Completion: 2021-12-15
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-02
• Last Update Posted: 2022-02-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Adult Patients with OTC Deficiency	No Intervention	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.

Primary Outcome Measures

Name	Time	Method
Hyperammonemia Indicator Questionnaire (HI-Q)	Up to 96 weeks	Patient-reported outcome (PRO) for symptoms of hyperammonemia
Rate of Hyperammonemic Crisis (HAC)	Up to 96 weeks
OTC Genotype	Up to 96 weeks	Genotype in blood
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
Cognitive assessment	Up to 96 weeks	Cogstate platform
OTC Deficiency Impact Questionnaire (OTC-D-IQ)	Up to 96 weeks	PRO for impact of hyperammonemia

Trial Locations

Locations (1)

PPD Phase 1 Clinic - Orlando; 🇺🇸 Orlando, Florida, United States