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

Brief Title

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

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 OTC Deficiency

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 Description

      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 IV doses of DTX301.

      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.

      This study was previously posted by Dimension Therapeutics, which has been acquired by

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

The incidence of treatment-related adverse events by dosing group

Secondary Outcome

 Change in baseline in ureagenesis rate


Ornithine Transcarbamylase (OTC) Deficiency



Study Arms / Comparison Groups

 Dose 1: 2.0 × 10^12 GC/kg
Description:  DTX301 (scAAV8OTC) will be administered as a single peripheral IV infusion. Sodium acetate is used as a tracer to measure the rate of ureagenesis.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 2017

Completion Date

December 15, 2021

Primary Completion Date

December 15, 2021

Eligibility Criteria

        Key Inclusion Criteria:

          1. Males and females ≥18 years of age with documented diagnosis of late onset (defined as
             first manifestation of signs and symptoms at ≥1 month of age) OTC deficiency,
             confirmed via enzymatic, biochemical, or molecular testing

          2. Documented history of ≥1 symptomatic hyperammonemia event with ammonia ≥100 µmol/L.

          3. Subject's OTC deficiency is stable as evidenced by either a) no clinical symptoms of
             hyperammonemia OR b) an ammonia level <100 µmol/L within the 4 week period preceding
             the Screening visit.

          4. On ongoing daily stable dose of ammonia scavenger therapy for ≥4 weeks.

          5. Males and all females of childbearing potential must be willing to use effective
             contraception at the time of administration of gene transfer and for the 52 weeks
             following administration of DTX301

        Key Exclusion Criteria:

          1. At Screening or Baseline (Day 0), plasma ammonia level ≥ 100 μmol/L for patients who
             historically maintain normal ammonia levels; OR plasma ammonia level ≥ 200 μmol/L for
             patients who historically are not able to fully control ammonia levels with baseline
             management; OR signs and symptoms of hyperammonemia.

          2. Liver transplant, including hepatocyte cell therapy/transplant.

          3. History of liver disease

          4. Significant hepatic inflammation or cirrhosis

          5. Serum creatinine >2.0 mg/dL.

          6. Participation in another investigational medicine study (including another gene
             transfer trial) within 3 months of Screening

          7. Pregnant or nursing

        Note additional inclusion/exclusion criteria may apply, per protocol.




18 Years - N/A

Accepts Healthy Volunteers



Medical Director, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Ultragenyx Pharmaceutical Inc

Study Sponsor

Medical Director, Study Director, Ultragenyx Pharmaceutical Inc

Verification Date

January 2022