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

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

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 Overview

• Status: Terminated
• Conditions: Ornithine Transcarbamylase Deficiency
• Intervention / Treatment: Other: No Intervention

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 Type: Observational
• Enrollment (Actual): 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • PPD Phase 1 Clinic - Orlando

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Adult Patients with OTC Deficiency; 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; No Intervention

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc
• Investigators: Study Director: Medical Director, Ultragenyx Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2020
• Primary Completion (Actual): December 15, 2021
• Study Completion (Actual): December 15, 2021

Study Registration Dates

• First Submitted: January 15, 2021
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): February 18, 2022
• Last Update Submitted That Met QC Criteria: February 2, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Neonatal; OTC; OTC Deficiency; Late Onset; Asymptomatic Carrier
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Urea Cycle Disorders, Inborn; Ornithine Carbamoyltransferase Deficiency Disease
• Other Study ID Numbers: DTX301-CL102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No