Clinical Trial: Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset OTC Deficiency

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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

Brief Summary: A Phase 1/2, open-label dose-finding safety study of single ascending doses of DTX301 in adults with late-onset OTC Deficiency

Detailed 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 establish a dose of DTX301 that has a clinically meaningful increase in the rate of ureagenesis. Eligible subjects 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 subjects in a dosing cohort.

Subjects will be followed for 52 weeks after dosing. After completion of this study, subjects 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.


Sponsor: Dimension Therapeutics

Current Primary Outcome: The incidence of treatment-related adverse events by dosing group [ Time Frame: 52 weeks ]

The incidence of adverse events (AEs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) for each dosing cohort, assessed by severity and relationship to study product.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in baseline in ureagenesis rate [ Time Frame: 52 weeks ]
    The change from baseline in the rate of ureagenesis (as measured by the generation of [13C]urea) as determined over time to 52 weeks after the IV administration of DTX301.
  • Change in baseline 24 hour area under the curve of ammonia [ Time Frame: 52 weeks ]
    The change from baseline (Day 0) in area under the curve from time zero to 24 hours (AUC0 24) for serum ammonia over time to 52 weeks after IV administration of DTX301


Original Secondary Outcome: Same as current

Information By: Dimension Therapeutics

Dates:
Date Received: December 9, 2016
Date Started: January 2017
Date Completion: November 2018
Last Updated: May 18, 2017
Last Verified: May 2017