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Study of UX701 Gene Transfer for the Treatment of Wilson Disease

Primary Purpose

Wilson Disease

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
UX701
Placebo
Sponsored by
Ultragenyx Pharmaceutical Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Wilson Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Confirmed diagnosis of Wilson disease
  • Ongoing copper chelator (ie, penicillamine, trientine) and/or zinc therapy for at least 12 months at screening, with no medication or dose changes for at least 6 months at screening.
  • Stable Wilson disease as evidenced by stable 24-hour urinary copper concentration during the Screening Period
  • Ongoing restriction of high copper containing foods for at least 12 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 12 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

Sites / Locations

  • University of California Los AngelesRecruiting
  • Stanford UniversityRecruiting
  • University of California DavisRecruiting
  • Northwestern UniversityRecruiting
  • Indiana UniversityRecruiting
  • Massachusetts General HospitalRecruiting
  • University of MichiganRecruiting
  • Duke University Medical CenterRecruiting
  • Vanderbilt University Medical CenterRecruiting
  • University of UtahRecruiting
  • University of VirginiaRecruiting
  • Seattle Children's HospitalRecruiting
  • Gordon and Leslie Diamond Health Care CentreRecruiting
  • Centro Hospitalar Universitário Lisboa NorteRecruiting
  • Centro Hospitalar Universitário de São JoãoRecruiting
  • Hospital Universitario Vall d'Hebron - PPDSRecruiting
  • Kings College NHS FoundationRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Stage 1: UX701 Dose Level 1

Stage 1: UX701 Dose Level 2

Stage 1: UX701 Dose Level 3

Stage 2: UX701 or Placebo

Stage 3: Placebo or UX701

Arm Description

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

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

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

Participants randomized 2:1 to receive UX701 or Placebo. Participants randomized to UX701 receive a single, peripheral IV infusion of UX701 at a dose selected in Stage 1. Participants randomized to placebo will receive a single, peripheral IV infusion of normal saline (placebo).

Participants randomized in Stage 2 to UX701 will receive a single, peripheral IV infusion of normal saline (placebo). Participants randomized in Stage 2 to placebo will be eligible for a single, peripheral IV infusion of UX701 at the selected dose.

Outcomes

Primary Outcome Measures

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
Stage 1: Change in 24-hour Urinary Copper Concentration from Baseline at Week 52
Stage 1: Change in Total Copper from Baseline at Week 52
Stage 1: Change in Ceruloplasmin from Baseline at Week 52
Stage 1: Change in Non-Ceruloplasmin-bound Copper (NCC) from Baseline at Week 52
Stage 1: Change in Free Copper from Baseline at Week 52
Stage 1: Change in Ceruloplasmin Activity from Baseline at Week 52
Stage 1: Percent Reduction in Standard of Care (SOC) Medication by Week 52
Stage 1: Number of Participants Who Discontinue SOC Medication by Week 52
Stage 1: Number of Consecutive Weeks off SOC Medication at Week 52
Stage 2: Change in 24-hour Urinary Copper Concentration from Baseline at Week 52, Evaluated for Superiority
Stage 2: Percent Reduction in SOC Medication by Week 52, Evaluated for Superiority

Secondary Outcome Measures

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

Full Information

First Posted
May 7, 2021
Last Updated
October 9, 2023
Sponsor
Ultragenyx Pharmaceutical Inc
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1. Study Identification

Unique Protocol Identification Number
NCT04884815
Brief Title
Study of UX701 Gene Transfer for the Treatment of Wilson Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 27, 2021 (Actual)
Primary Completion Date
January 2026 (Anticipated)
Study Completion Date
January 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ultragenyx Pharmaceutical Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wilson Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
78 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Stage 1: UX701 Dose Level 1
Arm Type
Experimental
Arm Description
Participants receive a single, peripheral intravenous (IV) infusion of UX701 at dose level 1.
Arm Title
Stage 1: UX701 Dose Level 2
Arm Type
Experimental
Arm Description
Participants receive a single, peripheral IV infusion of UX701 at dose level 2.
Arm Title
Stage 1: UX701 Dose Level 3
Arm Type
Experimental
Arm Description
Participants receive a single, peripheral IV infusion of UX701 at dose level 3.
Arm Title
Stage 2: UX701 or Placebo
Arm Type
Experimental
Arm Description
Participants randomized 2:1 to receive UX701 or Placebo. Participants randomized to UX701 receive a single, peripheral IV infusion of UX701 at a dose selected in Stage 1. Participants randomized to placebo will receive a single, peripheral IV infusion of normal saline (placebo).
Arm Title
Stage 3: Placebo or UX701
Arm Type
Experimental
Arm Description
Participants randomized in Stage 2 to UX701 will receive a single, peripheral IV infusion of normal saline (placebo). Participants randomized in Stage 2 to placebo will be eligible for a single, peripheral IV infusion of UX701 at the selected dose.
Intervention Type
Genetic
Intervention Name(s)
UX701
Intervention Description
Nonreplicating, recombinant gene transfer vector
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Normal saline
Primary Outcome Measure Information:
Title
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
Time Frame
Up to Week 52
Title
Stage 1: Change in 24-hour Urinary Copper Concentration from Baseline at Week 52
Time Frame
Baseline, Week 52
Title
Stage 1: Change in Total Copper from Baseline at Week 52
Time Frame
Baseline, Week 52
Title
Stage 1: Change in Ceruloplasmin from Baseline at Week 52
Time Frame
Baseline, Week 52
Title
Stage 1: Change in Non-Ceruloplasmin-bound Copper (NCC) from Baseline at Week 52
Time Frame
Baseline, Week 52
Title
Stage 1: Change in Free Copper from Baseline at Week 52
Time Frame
Baseline, Week 52
Title
Stage 1: Change in Ceruloplasmin Activity from Baseline at Week 52
Time Frame
Baseline, Week 52
Title
Stage 1: Percent Reduction in Standard of Care (SOC) Medication by Week 52
Time Frame
Week 52
Title
Stage 1: Number of Participants Who Discontinue SOC Medication by Week 52
Time Frame
Week 52
Title
Stage 1: Number of Consecutive Weeks off SOC Medication at Week 52
Time Frame
Week 52
Title
Stage 2: Change in 24-hour Urinary Copper Concentration from Baseline at Week 52, Evaluated for Superiority
Time Frame
Baseline, Week 52
Title
Stage 2: Percent Reduction in SOC Medication by Week 52, Evaluated for Superiority
Time Frame
Week 52
Secondary Outcome Measure Information:
Title
Stage 2: Change in Ceruloplasmin Activity Levels from Baseline at Week 52, Evaluated for Superiority
Time Frame
Baseline, Week 52
Title
Stage 2: Number of Participants who Discontinue SOC Medication by Week 52
Time Frame
Week 52
Title
Stage 2: Change in FACIT-Fatigue Scale Score from Baseline at Week 52
Time Frame
Baseline, Week 52
Title
Stage 2: Change in Liver Copper Concentration Assessed by Liver Biopsy from Baseline at Week 52
Time Frame
Baseline, Week 52
Other Pre-specified Outcome Measures:
Title
Stage 2: Development of Anti-ATP7B Antibodies
Time Frame
Up to Week 104
Title
Stage 2: Incidence of TEAEs, TESAEs, AESIs, Treatment-Related TEAEs, and Treatment-Related TESAEs
Time Frame
Up to Week 312

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Patients Contact: Trial Recruitment
Phone
1-888-756-8657
Email
trialrecruitment@ultragenyx.com
First Name & Middle Initial & Last Name or Official Title & Degree
HCPs Contact: Medical Information
Phone
1-888-756-8657
Email
medinfo@ultragenyx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Ultragenyx Pharmaceutical Inc
Official's Role
Study Director
Facility Information:
Facility Name
University of California Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Diane Yang
Email
ddyang@mednet.ucla.edu
First Name & Middle Initial & Last Name & Degree
Lily Travis
Email
ltravis@mednet.ucla.edu
First Name & Middle Initial & Last Name & Degree
Jeff Bronstein
Facility Name
Stanford University
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vyvian Ngo
Email
vyviann@stanford.edu
First Name & Middle Initial & Last Name & Degree
Swati Toppo
Email
stoppo@stanford.edu
First Name & Middle Initial & Last Name & Degree
Paul Kwo
Facility Name
University of California Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817-1348
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura Ocuman
Email
mrocumen@ucdavis.edu
First Name & Middle Initial & Last Name & Degree
Valentina Medici
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ZsaZsa Brown
Email
zsazsa.brown@northwestern.edu
First Name & Middle Initial & Last Name & Degree
Danny Bega
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Holly King
Email
hrking1@iu.edu
First Name & Middle Initial & Last Name & Degree
Kelsey Green
Email
greenke@iu.edu
First Name & Middle Initial & Last Name & Degree
Craig Lammert
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joni Cotter
Email
jcotter@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Russell Goodman
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashley Page
Email
ashpage@med.umich.edu
First Name & Middle Initial & Last Name & Degree
Zachary Balogh
Email
zbalogh@med.umich.edu
First Name & Middle Initial & Last Name & Degree
Frederik Askari
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Megan Beyer
Email
megan.beyer@duke.edu
First Name & Middle Initial & Last Name & Degree
Janet Wootton
Email
janet.wootton@duke.edu
First Name & Middle Initial & Last Name & Degree
Andrew Muir
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212-2700
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathryn Campbell
Email
kathryn.e.campbell@vumc.org
First Name & Middle Initial & Last Name & Degree
Andrew Scanga
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shambrae Will
Email
shambrae.will@hsc.utah.edu
First Name & Middle Initial & Last Name & Degree
Jamil Mcpherson
Email
jamil.mcpherson@hsc.utah.edu
First Name & Middle Initial & Last Name & Degree
Juan Gallegos-Orozco
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908-0001
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca Hudnall
Email
rh4n@uvahealth.org
First Name & Middle Initial & Last Name & Degree
Stephen Caldwell
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Phi Duong
Email
phi.duong@seattlechildrens.org
First Name & Middle Initial & Last Name & Degree
Sihoun Hahn
Facility Name
Gordon and Leslie Diamond Health Care Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Individual Site Status
Recruiting
Facility Name
Centro Hospitalar Universitário Lisboa Norte
City
Lisboa
State/Province
Lisbon
ZIP/Postal Code
1649-035
Country
Portugal
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susana Ponte
Email
sp.ensaios.cic@gmail.com
First Name & Middle Initial & Last Name & Degree
Sofia Carvalhana
Facility Name
Centro Hospitalar Universitário de São João
City
Porto
ZIP/Postal Code
4200-319
Country
Portugal
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eduarda Goncalves
Email
eduarda.isabel.goncalves@chsj.min-saude.pt
First Name & Middle Initial & Last Name & Degree
Helder Manuel Casal Cardoso
Facility Name
Hospital Universitario Vall d'Hebron - PPDS
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mauricio Larrarte
Email
carlos.larrarte@vhir.org
First Name & Middle Initial & Last Name & Degree
Jesus Quintero
Facility Name
Kings College NHS Foundation
City
London
State/Province
Surrey
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aftab Ala, MD, PhD
Email
aftabala@nhs.net

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.
Links:
URL
https://ultrarareadvocacy.com/wilson-disease-wd/
Description
Ultragenyx Patient Advocacy/Wilson Disease Information

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Study of UX701 Gene Transfer for the Treatment of Wilson Disease

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