A Phase 1/2/3 Study of UX701 Gene Therapy in Adults With Wilson Disease

NCT04884815 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: UX701-CL3012020-005266-342022-502873-40-00
• Study Type: interventional
• Target: 82
• Locations: 5 countries
• Sites: 16

Brief Summary

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.

Conditions

Wilson Disease

Outcome Measures

Primary Outcomes (13)

• 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-bound 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

Secondary Outcomes (4)

• 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 FACIT-Fatigue Scale Score from Baseline at Week 52

  Baseline, Week 52

• Stage 2: Change in Liver Copper Concentration Assessed by Liver Biopsy from Baseline at Week 52

  Baseline, Week 52

Other Outcomes (2)

• 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

Study Arms (6)

Stage 1: UX701 Dose Level 1

EXPERIMENTAL

Participants receive a single, peripheral intravenous (IV) infusion of UX701 at dose level 1.

Genetic: UX701

Stage 1: UX701 Dose Level 2

EXPERIMENTAL

Participants receive a single, peripheral IV infusion of UX701 at dose level 2.

Genetic: UX701

Stage 1: UX701 Dose Level 3

EXPERIMENTAL

Participants receive a single, peripheral IV infusion of UX701 at dose level 3.

Genetic: UX701

Stage 1: UX701 Dose Level 4

EXPERIMENTAL

Participants receive a single, peripheral IV infusion of UX701 at dose level 4.

Genetic: UX701

Stage 2: UX701 at Selected Dose

EXPERIMENTAL

Participants randomized to UX701 receive a single, peripheral IV infusion of UX701 at the selected dose.

Genetic: UX701

Stage 2: Standard of Care (SOC) to UX701

EXPERIMENTAL

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; Drug: Standard of Care (SOC)

Interventions

UX701 GENETIC

Nonreplicating, recombinant gene transfer vector

Also known as: rivunatpagene miziparvovec

Stage 1: UX701 Dose Level 1; Stage 1: UX701 Dose Level 2; Stage 1: UX701 Dose Level 3; Stage 1: UX701 Dose Level 4; Stage 2: Standard of Care (SOC) to UX701; Stage 2: UX701 at Selected Dose

Standard of Care (SOC) DRUG

SOC treatment (i.e., copper chelators and/or zinc) administered according to standard regimens.

Stage 2: Standard of Care (SOC) to UX701

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (16)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University

Redwood City, California, 94063, United States

Location

University of California Davis

Sacramento, California, 95817-1348, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212-2700, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Gordon and Leslie Diamond Health Care Centre

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Centro Hospitalar Universitário Lisboa Norte

Lisbon, Lisbon District, 1649-035, Portugal

Location

Centro Hospitalar Universitário de São João

Porto, Porto District, 4200-319, Portugal

Location

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, 08035, Spain

Location

Kings College NHS Foundation

London, Surrey, SE5 9RS, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Hepatolenticular Degeneration

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Those responsible for reviewing MRI assessments, ophthalmology assessments, and analyzing liver biopsy samples will be double-blinded.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: May 13, 2021
• Study Start: September 27, 2021
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2034
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); ES (1); CA (1); PT (2); GB (1)