Gene therapy for adults with Wilson disease

An Operationally Seamless Phase 1/2/3 Study Consisting of a Safety and Dose-finding Phase 1/2 and Randomized, Open-label, Active-controlled Phase 3 to Evaluate UX701 AAV Gene Therapy in Adults With Wilson Disease

This study is testing a new gene therapy called UX701 to see if it can safely help adults with Wilson disease feel better compared to standard treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 82 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ultragenyx Pharmaceutical Inc (Industry-sponsored)
• Drugs / interventions: rituximab, eculizumab
• Locations: 17 sites (Los Angeles, California and 16 other locations)
• Trial ID: NCT04884815 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of a gene therapy called UX701 in adults diagnosed with Wilson disease. It consists of three stages: the first stage focuses on determining the safest and most effective dose of UX701, while the second stage compares this selected dose against standard care in a randomized manner. The final stage involves long-term follow-up to assess the ongoing safety and clinical benefits of the treatment over at least five years.

Who should consider this trial

Good fit: Ideal candidates are adults with a confirmed diagnosis of Wilson disease who have been stable on copper chelation therapy for at least two months.

Not a fit: Patients with a history of liver transplant or those who are noncompliant with copper chelation therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this gene therapy could provide a new treatment option that effectively regulates copper levels in patients with Wilson disease.

How similar studies have performed: While gene therapy for Wilson disease is a novel approach, similar gene therapies for other genetic disorders have shown promising results in previous studies.

Eligibility criteria

Key Inclusion Criteria:

* Confirmed diagnosis of Wilson disease based on genetic confirmation of heterozygous or homozygous biallelic ATP7B mutation.
* Stable Wilson disease as evidenced by ongoing copper chelator (ie, penicillamine, trientine) and/or zinc therapy for at least 2 months at screening, with no medication or dose changes for at least 2 months at screening.
* Ongoing restriction of high copper containing foods for at least 2 months at Screening and continued through study participation.
* Willing and able to comply with all study procedures and requirements, including frequent blood collection, total urine collection over a 24-hour period, patient-reported outcome assessments, and long-term follow-up

Key Exclusion Criteria:

* Detectable pre-existing antibodies to the AAV9 capsid.
* Stage 1 only: History of copper chelator or zinc therapy noncompliance, in the Investigator's judgment, within 6 months prior to Screening.
* History of liver transplant.
* Active decompensated hepatic cirrhosis or history of hepatic encephalopathy.
* Significant hepatic inflammation as evidenced by laboratory abnormalities.
* Model for End-Stage Liver Disease (MELD) score \> 13.
* Hemoglobin \< 9 g/dL
* Presence of Stage 3 or higher chronic kidney disease based on estimated glomerular filtration rate \< 60 mL/min/1.73 m2.
* Marked neurological deficit or compromise that, in the Investigator's opinion, would interfere with the subject's safety or ability to participate in the study.
* Moderate to severe depression, recent or active suicidal ideation with intent or suicidal behavior, psychosis, or unstable psychiatric illness.
* Known hypersensitivity to UX701 or its excipients, copper chelators, zinc, rituximab, tacrolimus, corticosteroids, or eculizumab that, in the Investigator's judgement, places the participant at increased risk for adverse events.
* Participation in another gene transfer study or use of another gene transfer product before or during study participation.
* Subjects with known hypersensitivity to amide-containing local anesthetics are excluded from participating in the optional liver biopsy substudy.

Note: Other protocol defined Inclusion/ Exclusion criteria may apply

Where this trial is running

Los Angeles, California and 16 other locations

• University of California Los Angeles — Los Angeles, California, United States (Recruiting)
• Stanford University — Redwood City, California, United States (Recruiting)
• University of California Davis — Sacramento, California, United States (Recruiting)
• Northwestern University — Chicago, Illinois, United States (Recruiting)
• Indiana University — Indianapolis, Indiana, United States (Active_not_recruiting)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Active_not_recruiting)
• University of Michigan — Ann Arbor, Michigan, United States (Recruiting)
• Duke University Medical Center — Durham, North Carolina, United States (Active_not_recruiting)
• University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States (Not_yet_recruiting)
• Vanderbilt University Medical Center — Nashville, Tennessee, United States (Active_not_recruiting)
• University of Utah — Salt Lake City, Utah, United States (Active_not_recruiting)
• Seattle Children's Hospital — Seattle, Washington, United States (Recruiting)
• Gordon and Leslie Diamond Health Care Centre — Vancouver, British Columbia, Canada (Active_not_recruiting)
• Centro Hospitalar Universitário Lisboa Norte — Lisboa, Lisbon, Portugal (Active_not_recruiting)
• Centro Hospitalar Universitário de São João — Porto, Portugal (Active_not_recruiting)
• Hospital Universitario Vall d'Hebron - PPDS — Barcelona, Spain (Active_not_recruiting)
• Kings College NHS Foundation — London, Surrey, United Kingdom (Active_not_recruiting)

Study contacts

• Study coordinator: Patients Contact: Trial Recruitment

Conditions Wilson Disease