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Study of UX701 Gene Transfer for the Treatment of Wilson Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04884815
Recruitment Status : Active, not recruiting
First Posted : May 13, 2021
Last Update Posted : March 29, 2024
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Description
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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.

Condition or disease Intervention/treatment Phase
Wilson Disease Genetic: UX701 Other: Placebo Phase 1 Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 27, 2021
Estimated Primary Completion Date : August 2026
Estimated Study Completion Date : November 2031

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
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
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
Experimental: Stage 2: UX701 or Placebo
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).
 Genetic: UX701
Nonreplicating, recombinant gene transfer vector

Other: Placebo
Normal saline
Experimental: Stage 3: Placebo or UX701
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.
 Genetic: UX701
Nonreplicating, recombinant gene transfer vector

Other: Placebo
Normal saline


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
  2. Stage 1: Change in 24-hour Urinary Copper Concentration from Baseline at Week 52 [ Time Frame: Baseline, Week 52 ]
  3. Stage 1: Change in Total Copper from Baseline at Week 52 [ Time Frame: Baseline, Week 52 ]
  4. Stage 1: Change in Ceruloplasmin from Baseline at Week 52 [ Time Frame: Baseline, Week 52 ]
  5. Stage 1: Change in Non-Ceruloplasmin-bound Copper (NCC) from Baseline at Week 52 [ Time Frame: Baseline, Week 52 ]
  6. Stage 1: Change in Free Copper from Baseline at Week 52 [ Time Frame: Baseline, Week 52 ]
  7. Stage 1: Change in Ceruloplasmin Activity from Baseline at Week 52 [ Time Frame: Baseline, Week 52 ]
  8. Stage 1: Percent Reduction in Standard of Care (SOC) Medication by Week 52 [ Time Frame: Week 52 ]
  9. Stage 1: Number of Participants Who Discontinue SOC Medication by Week 52 [ Time Frame: Week 52 ]
  10. Stage 1: Number of Consecutive Weeks off SOC Medication at Week 52 [ Time Frame: Week 52 ]
  11. Stage 2: Change in 24-hour Urinary Copper Concentration from Baseline at Week 52, Evaluated for Superiority [ Time Frame: Baseline, Week 52 ]
  12. Stage 2: Percent Reduction in SOC Medication by Week 52, Evaluated for Superiority [ Time Frame: Week 52 ]

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

Other Outcome Measures:
  1. Stage 2: Development of Anti-ATP7B Antibodies [ Time Frame: Up to Week 104 ]
  2. Stage 2: Incidence of TEAEs, TESAEs, AESIs, Treatment-Related TEAEs, and Treatment-Related TESAEs [ Time Frame: Up to Week 312 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04884815


Locations
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Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Investigators
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Study Director: Medical Director Ultragenyx Pharmaceutical Inc
More Information
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Additional Information:

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Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT04884815    
Other Study ID Numbers: UX701-CL301
2020-005266-34 ( EudraCT Number )
2022-502873-40-00 ( Other Identifier: EU CT Number )
First Posted: May 13, 2021    Key Record Dates
Last Update Posted: March 29, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hepatolenticular Degeneration
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
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors
Metabolic Diseases