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

NCT04717453 | Terminated FDA Drug

• 1 other identifier: DTX301-CL102
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Ornithine Transcarbamylase Deficiency

Keywords

OTC; OTC Deficiency; Neonatal; Late Onset; Asymptomatic Carrier

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (1)

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

Interventions

No Intervention OTHER

No Intervention

Adult Patients with OTC Deficiency

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (1)

PPD Phase 1 Clinic - Orlando

Orlando, Florida, 32806, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

DNA for OTC genotype

MeSH Terms

Conditions

Ornithine Carbamoyltransferase Deficiency Disease

Condition Hierarchy (Ancestors)

Urea Cycle Disorders, Inborn; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Medical Director

  Ultragenyx Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2021
• First Posted: January 22, 2021
• Study Start: October 6, 2020
• Primary Completion: December 15, 2021
• Study Completion: December 15, 2021
• Last Updated: February 18, 2022

Record last verified: 2022-02

Locations

US (1)