NCT02991144

Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset Ornithine Transcarbamylase (OTC) Deficiency

A Phase 1/2, Open-Label Safety and Dose-Finding Study of Adeno-Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Adults With Late-Onset OTC Deficiency

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: Ultragenyx Pharmaceutical Inc · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1/2, open-label, single arm, multicenter, safety and dose finding study of DTX301 in adults with late-onset OTC deficiency. The primary objective of the study is to determine the safety of single intravenous (IV) doses of DTX301.

Detailed description

Eligible participants will receive a single IV infusion of DTX301. Dose escalation will be conducted according to a model that uses the collected data to predict the safety profile of the dose in order to determine the optimal biological dose (OBD). The decision to proceed to the next dose cohort will be made after the data monitoring committee (DMC) has evaluated the safety data for all participants in a dosing cohort. Participants will be followed for 52 weeks after dosing. After completion of this study, participants will be asked to enroll in a 4-year extension study to evaluate the long term (a total of 5 years) safety and efficacy of DTX301. This study was previously posted by Dimension Therapeutics, which has been acquired by Ultragenyx.

Conditions

• Ornithine Transcarbamylase (OTC) Deficiency

Interventions

Type	Name	Description
GENETIC	scAAV8OTC	non-replicating, recombinant scAAV8 encoding human ornithine transcarbamylase (OTC)
DRUG	Reactive Corticosteroid Taper Regimen	Oral prednisone \[or oral prednisolone\] 60 mg/day week 1, 40 mg/day Week 2, 30 mg/day Weeks 3 and 4, tapered by 5 mg/week Week 5 and beyond until liver enzymes return to baseline levels. Corticosteroid treatment will be considered when a participant's alanine aminotransferase (ALT) level exceeded the upper limit of normal (ULN) and the ALT increase was considered by the Investigator to be related to DTX301.
DRUG	Prophylactic Corticosteroid Taper Regimen	Oral prednisone \[or oral prednisolone\] 60 mg/day at least 5 days prior to DTX301 administration, tapered over 9 weeks. A prophylactic corticosteroid taper regimen will be administered to prevent or minimize transient vector-induced hepatic effects.

Timeline

• Start date: 2017-07-31
• Primary completion: 2021-12-16
• Completion: 2021-12-16
• First posted: 2016-12-13
• Last updated: 2023-01-26
• Results posted: 2022-12-23

Locations

9 sites across 4 countries: United States, Canada, Spain, United Kingdom

Regulatory

• FDA-regulated drug study