A Phase 1/2/3 Study of UX701 Gene Therapy in 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

The primary objectives of this study are to evaluate the safety of single IV doses of UX701 in patients with Wilson disease, to select the UX701 dose with the best benefit/risk profile based on the totality of safety and efficacy data and to evaluate the effect of UX701 on copper regulation.

Study Overview

• Status: Active, not recruiting
• Conditions: Wilson Disease
• Intervention / Treatment: Genetic: UX701; Drug: Standard of Care (SOC)

Detailed Description

Stage 1 (Phase 1/2) is an open-label safety and dose-finding stage designed to evaluate the safety and efficacy of 4 dose levels of UX701 to establish initial safety of UX701 and select a safe and efficacious dose for further evaluation. Stage 2 (Phase 3) is a randomized, open-label, active-controlled stage to evaluate the safety and efficacy of UX701 using the dose selected in Stage 1. Stage 3 is a long-term follow-up stage designed to evaluate the safety, efficacy, and clinical benefit of UX701 for at least 5 years from the time of UX701 administration.

Participants who receive UX701 will receive premedication, prophylactic oral corticosteroids and immunomodulation therapy.

• Study Type: Interventional
• Enrollment (Estimated): 82
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Gordon and Leslie Diamond Health Care Centre
• Portugal
  • Lisbon District
    • Lisbon, Lisbon District, Portugal, 1649-035
      • Centro Hospitalar Universitario Lisboa Norte
  • Porto District
    • Porto, Porto District, Portugal, 4200-319
      • Centro Hospitalar Universitário De São João
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron - PPDS
• United Kingdom
  • Surrey
    • London, Surrey, United Kingdom, SE5 9RS
      • Kings College NHS Foundation
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Redwood City, California, United States, 94063
      • Stanford University
    • Sacramento, California, United States, 95817-1348
      • University of California Davis
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212-2700
      • Vanderbilt University Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1: UX701 Dose Level 1; Participants receive a single, peripheral intravenous (IV) infusion of UX701 at dose level 1.	Genetic: UX701; Nonreplicating, recombinant gene transfer vector; Other Names: rivunatpagene miziparvovec
Experimental: Stage 1: UX701 Dose Level 2; Participants receive a single, peripheral IV infusion of UX701 at dose level 2.	Genetic: UX701; Nonreplicating, recombinant gene transfer vector; Other Names: rivunatpagene miziparvovec
Experimental: Stage 1: UX701 Dose Level 3; Participants receive a single, peripheral IV infusion of UX701 at dose level 3.	Genetic: UX701; Nonreplicating, recombinant gene transfer vector; Other Names: rivunatpagene miziparvovec
Experimental: Stage 1: UX701 Dose Level 4; Participants receive a single, peripheral IV infusion of UX701 at dose level 4.	Genetic: UX701; Nonreplicating, recombinant gene transfer vector; Other Names: rivunatpagene miziparvovec
Experimental: Stage 2: UX701 at Selected Dose; Participants randomized to UX701 receive a single, peripheral IV infusion of UX701 at the selected dose.	Genetic: UX701; Nonreplicating, recombinant gene transfer vector; Other Names: rivunatpagene miziparvovec
Experimental: Stage 2: Standard of Care (SOC) to UX701; Participants randomized to SOC will continue their baseline SOC medications for 52 weeks, followed by a single, peripheral IV infusion of UX701 at the selected dose. Following UX701 administration, participants will be evaluated for modification of their SOC medications.	Genetic: UX701; Nonreplicating, recombinant gene transfer vector; Other Names: rivunatpagene miziparvovec; Drug: Standard of Care (SOC); SOC treatment (i.e., copper chelators and/or zinc) administered according to standard regimens.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Stage 1: Incidence of Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs), Treatment-Related TEAEs, and Treatment-Related TESAEs	Up to Week 52
Stage 1: Change in 24-hour Urinary Copper Concentration from Baseline at Week 52	Baseline, Week 52
Stage 1: Change in Total Copper from Baseline at Week 52	Baseline, Week 52
Stage 1: Change in Ceruloplasmin from Baseline at Week 52	Baseline, Week 52
Stage 1: Change in Non-Ceruloplasmin-bound Copper (NCC) from Baseline at Week 52	Baseline, Week 52
Stage 1: Change in Free Copper from Baseline at Week 52	Baseline, Week 52
Stage 1: Change in Ceruloplasmin Activity from Baseline at Week 52	Baseline, Week 52
Stage 1: Percent Reduction in Standard of Care (SOC) Medication by Week 52	Week 52
Stage 1: Number of Participants Who Discontinue SOC Medication by Week 52	Week 52
Stage 1: Number of Consecutive Weeks off SOC Medication at Week 52	Week 52
Stage 2: Change in 24-hour Urinary Copper Concentration from Baseline at Week 52, Evaluated for Superiority	Baseline, Week 52
Stage 2: Percent Reduction in SOC Medication by Week 52, Evaluated for Superiority	Week 52
Stage 1: Change in Ceruloplasmin-bound Copper from Baseline at Week 52	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Stage 2: Change in Ceruloplasmin Activity Levels from Baseline at Week 52, Evaluated for Superiority	Baseline, Week 52
Stage 2: Number of Participants who Discontinue SOC Medication by Week 52	Week 52
Stage 2: Change in Liver Copper Concentration Assessed by Liver Biopsy from Baseline at Week 52	Baseline, Week 52
Stage 2: Change in FACIT-Fatigue Scale Score from Baseline at Week 52	Baseline, Week 52

Other Outcome Measures

Outcome Measure	Time Frame
Stage 2: Development of Anti-ATP7B Antibodies	Up to Week 104
Stage 2: Incidence of TEAEs, TESAEs, AESIs, Treatment-Related TEAEs, and Treatment-Related TESAEs	Up to Week 312

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc
• Investigators: Study Director: Medical Director, Ultragenyx Pharmaceutical Inc

Publications and helpful links

Helpful Links

• Ultragenyx Patient Advocacy/Wilson Disease Information
• Ultragenyx Wilson Disease (WD) Research Study Opportunities
• Ultragenyx Transparency Commitment

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2021
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2034

Study Registration Dates

• First Submitted: May 7, 2021
• First Submitted That Met QC Criteria: May 7, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Neurodegenerative Diseases; Liver Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Metal Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hepatolenticular Degeneration; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: UX701-CL301; 2020-005266-34 (EudraCT Number); 2022-502873-40-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to the rarity of Wilson Disease, individual patient data will not be shared in order to safeguard patient privacy. The study protocol and statistical analysis plan for this study will be available with the tabulated results once posted.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No