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

NCT ID: NCT04884815

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-27
• Study Completion Date: 2034-03-31

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.

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.

Conditions

Wilson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Stage 1: UX701 Dose Level 1

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

Group Type: EXPERIMENTAL

UX701

Intervention Type: GENETIC

Nonreplicating, recombinant gene transfer vector

Stage 1: UX701 Dose Level 2

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

Group Type: EXPERIMENTAL

UX701

Intervention Type: GENETIC

Nonreplicating, recombinant gene transfer vector

Stage 1: UX701 Dose Level 3

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

Group Type: EXPERIMENTAL

UX701

Intervention Type: GENETIC

Nonreplicating, recombinant gene transfer vector

Stage 1: UX701 Dose Level 4

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

Group Type: EXPERIMENTAL

UX701

Intervention Type: GENETIC

Nonreplicating, recombinant gene transfer vector

Stage 2: UX701 at Selected Dose

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

Group Type: EXPERIMENTAL

UX701

Intervention Type: GENETIC

Nonreplicating, recombinant gene transfer vector

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.

Group Type: EXPERIMENTAL

UX701

Intervention Type: GENETIC

Nonreplicating, recombinant gene transfer vector

Standard of Care (SOC)

Intervention Type: DRUG

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

Interventions

UX701

Nonreplicating, recombinant gene transfer vector

Intervention Type: GENETIC

Standard of Care (SOC)

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

Intervention Type: DRUG

Other Intervention Names

rivunatpagene miziparvovec

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Ultragenyx Pharmaceutical Inc

Locations

University of California Los Angeles

Los Angeles, California, United States

Stanford University

Redwood City, California, United States

University of California Davis

Sacramento, California, United States

Northwestern University

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Duke University Medical Center

Durham, North Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Utah

Salt Lake City, Utah, United States

Seattle Children's Hospital

Seattle, Washington, United States

Gordon and Leslie Diamond Health Care Centre

Vancouver, British Columbia, Canada

Centro Hospitalar Universitário Lisboa Norte

Lisbon, Lisbon District, Portugal

Centro Hospitalar Universitário de São João

Porto, Porto District, Portugal

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, , Spain

Kings College NHS Foundation

London, Surrey, United Kingdom

Countries

United States; Canada; Portugal; Spain; United Kingdom

Related Links

https://ultrarareadvocacy.com/wilson-disease-wd/

Ultragenyx Patient Advocacy/Wilson Disease Information

https://www.ultraclinicaltrials.com/WilsonDisease

Ultragenyx Wilson Disease (WD) Research Study Opportunities

https://www.ultragenyx.com/our-research/our-clinical-trial-transparency-commitment/

Ultragenyx Transparency Commitment

Other Identifiers

2020-005266-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2022-502873-40-00

Identifier Type: OTHER

Identifier Source: secondary_id

UX701-CL301

Identifier Type: -

Identifier Source: org_study_id