• Orinthine Transcarbamylase (OTC) Deficiency Gene Therapy Clinical Trial

    Gene Therapy

    Phone: 617-632-5064  

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

    Ornithine transcarbamylase (OTC) deficiency is an inherited disorder caused by a mutation in the OTC gene. Typically, the OTC gene provides instructions to make the ornithine transcarbamylase enzyme, which starts a reaction in liver cells that allows the body to process excess nitrogen. With an OTC deficiency, an overabundance of ammonia accumulates in the bloodstream. Ammonia can become toxic when levels are too high, and this can lead to complications with the nervous system and eventual damage to the liver.

    People with late-onset OTC deficiency may experience episodes of altered mental states, including erratic behavior, delirium, and reduced levels of consciousness. Vomiting, headaches, aversion to protein foods, and seizures can also occur. Late-onset OTC deficiency is less severe than neonatel-onset OTC deficiency and occurs in both males and females.

    This Phase I/II trial aims to determine the dose of DTX301, an investigational gene therapy, needed to increase the rate of ureagenesis in patients with late-onset OTC deficiency. Increased rates of ureagenesis would allow for the detoxification of ammonia from the blood. Eligible patients will start with a single IV infusion of DTX301, with dose escalation to follow as deemed appropriate.

    Inclusion Criteria:

    • Ages 18 years and older
    • Documented diagnosis of late-onset OTC deficiency (defined as showing the first signs and symptoms at 1 month of age or earlier), confirmed via enzymatic, biochemical, or molecular testing
    • Documented history of 1 or more symptomatic hyperammonemia events with ammonia
    • 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
    • On stable dose of ammonia scavenger therapy for 4 weeks or more
    • Males and all females of childbearing potential must be willing to use effective contraception at the time of the administration of gene transfer and for the 52 weeks following the administration of DTX301

    Exclusion Criteria:

    • Screening or baseline (Day 0) ammonia level greater than or equal to 100 µmol/L or signs and symptoms indicative of hyperammonemia during the 4-week period preceding Day 0
    • Liver transplant, including hepatocyte cell therapy/transplant
    • History of liver disease
    • Serum creatinine is greater than 2.0 mg/dL
    • Participation in another investigational medicine study (including another gene transfer trial) within 3 months of screening
    • History of a malignancy for which the subject has received treatment in the past 2 years (except for prostate cancer treated with watchful waiting or surgically removed non-melanoma skin cancer)

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