Study of UX701 Gene Transfer for the Treatment of Wilson Disease

Wilson Disease Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Seamless, Adaptive, Safety, Dose-Finding, and Phase 3 Clinical Study of UX701 AAV-Mediated Gene Transfer for the Treatment of Wilson Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04884815
• Other study ID #: UX701-CL301
• Secondary ID: 2020-005266-3420
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 27, 2021
• Est. completion date: November 2031

Study information

• Verified date: May 2024
• Source: Ultragenyx Pharmaceutical Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This study is a randomized, double-blind, placebo-controlled, seamless, adaptive Phase 1/2/3 clinical study of UX701 in patients with Wilson disease.

Stage 1 (Phase 1/2) is a nonrandomized, open-label safety and dose-finding stage designed to evaluate the safety and efficacy of 3 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, double-blind, placebo-controlled stage designed to evaluate the safety and efficacy of UX701 using the dose selected in Stage 1. Stage 3 is designed to evaluate the long-term safety, efficacy, and clinical benefit of UX701. All participants will be followed for at least 5 years from the time of UX701 administration.

Participants who receive UX701 will receive premedications and prophylactic oral corticosteroids. Participants who receive placebo will receive premedications and placebo oral corticosteroids to maintain the study blind.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 78
• Est. completion date: November 2031
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Confirmed diagnosis of Wilson disease

• Stable Wilson disease as evidenced by ongoing copper chelator (ie, penicillamine, trientine) and/or zinc therapy for at least 6 months at screening, with no medication or dose changes for at least 6 months at screening.

• Ongoing restriction of high copper containing foods for at least 6 months at Screening, 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.

• Decompensated hepatic cirrhosis or presence of advanced liver disease as evidenced by portal hypertension, ascites, splenomegaly, esophageal varices, 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.

• 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

Related Conditions & MeSH terms

• Wilson Disease

Intervention

Genetic:
• UX701
Nonreplicating, recombinant gene transfer vector

Other:
• Placebo
Normal saline

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ultragenyx Pharmaceutical Inc

Countries where clinical trial is conducted

United States,  Canada,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stage 2: Development of Anti-ATP7B Antibodies		Up to Week 104
Other	Stage 2: Incidence of TEAEs, TESAEs, AESIs, Treatment-Related TEAEs, and Treatment-Related TESAEs		Up to Week 312
Primary	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
Primary	Stage 1: Change in 24-hour Urinary Copper Concentration from Baseline at Week 52		Baseline, Week 52
Primary	Stage 1: Change in Total Copper from Baseline at Week 52		Baseline, Week 52
Primary	Stage 1: Change in Ceruloplasmin from Baseline at Week 52		Baseline, Week 52
Primary	Stage 1: Change in Non-Ceruloplasmin-bound Copper (NCC) from Baseline at Week 52		Baseline, Week 52
Primary	Stage 1: Change in Free Copper from Baseline at Week 52		Baseline, Week 52
Primary	Stage 1: Change in Ceruloplasmin Activity from Baseline at Week 52		Baseline, Week 52
Primary	Stage 1: Percent Reduction in Standard of Care (SOC) Medication by Week 52		Week 52
Primary	Stage 1: Number of Participants Who Discontinue SOC Medication by Week 52		Week 52
Primary	Stage 1: Number of Consecutive Weeks off SOC Medication at Week 52		Week 52
Primary	Stage 2: Change in 24-hour Urinary Copper Concentration from Baseline at Week 52, Evaluated for Superiority		Baseline, Week 52
Primary	Stage 2: Percent Reduction in SOC Medication by Week 52, Evaluated for Superiority		Week 52
Secondary	Stage 2: Change in Ceruloplasmin Activity Levels from Baseline at Week 52, Evaluated for Superiority		Baseline, Week 52
Secondary	Stage 2: Number of Participants who Discontinue SOC Medication by Week 52		Week 52
Secondary	Stage 2: Change in FACIT-Fatigue Scale Score from Baseline at Week 52		Baseline, Week 52
Secondary	Stage 2: Change in Liver Copper Concentration Assessed by Liver Biopsy from Baseline at Week 52		Baseline, Week 52

External Links

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