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

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.

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.

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.