Ultragenyx Pharmaceutical Inc. announced that it has successfully screened and enrolled multiple patients with Wilson disease into the baseline monitoring period prior to dosing in its pivotal, seamless Phase 1/2/3 study of UX701, the Cyprus2+ study. The company's investigational AAV9 gene therapy is designed to deliver stable expression of the ATP7B copper transporter following a single intravenous infusion, with the goal of establishing normal trafficking of copper in patients with Wilson disease. The study will enroll patients receiving ongoing standard of care medication for the treatment of Wilson disease (copper chelators and/or zinc) for at least 12 months, with no medication or dose changes for at least 6 months prior to enrollment. After initial screening that includes testing for pre-existing antibodies to the AAV9 capsid, patients will be evaluated to ensure stable measures of disease during a 4-to 12-week baseline monitoring period (including values for 24-hour urinary copper concentration, complete blood count, and liver function tests). Seamless Phase 1/2/3 study design: This study evaluating UX701 for the potential treatment of Wilson disease is designed with 3 seamless stages. During the first stage, the safety and efficacy of up to three dose levels of UX701 will be evaluated over the course of 52 weeks and a dose will be selected for further evaluation in stage 2. In this first stage, 27 patients will be randomized into three cohorts in a 2:1 ratio per cohort to receive UX701 at the dose level assigned for the cohort or placebo. The sequential doses to be evaluated are 5.0 x 10^12 GC/kg, 1.0 x 10^13 GC/kg, and 2.0 x 10^13 GC/kg. In stage 2, a new cohort of patients will be randomized 2:1 to receive the selected dose of UX701 or placebo. The primary safety and efficacy analyses will be conducted at Week 52 of stage 2. The primary efficacy endpoints are change in 24-hour urinary copper concentration and percent reduction in standard of care (SOC) medication by Week 52. After the initial 52-week study period, all patients will have long term follow up in stage 3. Patients randomized to placebo in stages 1 and 2 will be eligible to receive UX701 in stage 3.