Research

Individuals who meet any of the following exclusion criteria are not eligible to participate:

1. Detectable pre-existing antibodies to the AAV9 capsid (AAV9 DetectCDx).
2. Stage 1 only: History of copper chelator or zinc therapy noncompliance, in the Investigator's judgment, within 6 months prior to Screening.
3. History of liver transplant.
4. Decompensated hepatic cirrhosis or presence of advanced liver disease as evidenced by portal hypertension, ascites, splenomegaly, esophageal varices, or hepatic encephalopathy.
5. Significant hepatic inflammation as evidenced by any of the following laboratory abnormalities:
   • ALT or AST > 3.0 × ULN
   • Total bilirubin > 2.0 × ULN
   • Alkaline phosphatase > 2.5 × ULN
6. Model for End-Stage Liver Disease (MELD) score > 13.
7. Hemoglobin < 9 g/dL.
8. Presence of Stage 3 or higher chronic kidney disease based on estimated glomerular filtration rate < 60 mL/min/1.73 m2.
9. 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.
10. Moderate to severe depression, recent or active suicidal ideation with intent or suicidal behavior, psychosis, or unstable psychiatric illness meeting any of the following criteria:
    • Moderate to severe depression defined as a Beck Depression Inventory-II (BDI-II) score > 20 at Screening
    • History of suicide attempt (including actual, interrupted, or aborted attempt) within 5 years prior to Screening, or history of suicidal ideation with intent within 6 months prior to Screening − Patients with a history of suicide attempt more than 5 years prior to Screening should be evaluated by a mental health care professional before enrolling in the study
    • Columbia Suicide Severity Rating Scale (C-SSRS) assessment with a Yes response to Question 4 (past 6 months only) or Question 5 (past 6 months only) at Screening • Moderate to severe psychosis at Screening, defined as a total Brief Psychiatric Rating Scale (BPRS) score > 10 for the following questions: Question 3 (Emotional Withdrawal), Question 11 (Suspiciousness), Question 12 (Hallucinatory Behavior), Question 15 (Unusual Thought Content), and Question 16 (Blunted Affect) (Park et al., 2015)
    • History of psychiatric inpatient hospitalization within 1 year prior to Screening or psychiatric medication changes within 8 weeks prior to Screening 11. History of active or latent tuberculosis, history of positive purified protein derivative (PPD) or tine test, positive QuantiFERON-TB Gold tuberculosis test, or positive T-SPOT.TB test if QuantiFERON-TB Gold tuberculosis test is not available.
11. History of active or latent tuberculosis, history of positive purified protein derivative (PPD) or tine test, positive QuantiFERON-TB Gold tuberculosis test, or positive T-SPOT.TB test if QuantiFERON-TB Gold tuberculosis test is not available.
12. Presence of active hepatitis B virus infection as defined by the laboratory assessment criteria listed in Table 13.
13. Presence of active hepatitis C virus infection as defined by the laboratory assessment criteria listed in Table 14.
14. History of human immunodeficiency virus infection.
15. Presence or history of any condition that, in the Investigator's opinion, would interfere with participation, pose undue risk, or confound interpretation of study results. This includes any intercurrent febrile or nonfebrile illness during Screening, including common viral infections, influenza, and COVID-19 until full clinical recovery.
16. Pregnant or breastfeeding or planning to become pregnant (self or partner):
    • Stage 1: At any time during the 52 weeks following IP administration on Day 0
    • Stage 2: At any time during the 104 weeks following IP administration on Day 0
17. Female subject of childbearing potential who has a positive serum pregnancy test at Screening or a positive urine pregnancy test at Baseline, or who is unwilling to have additional pregnancy tests during the study. Female subjects are considered not of childbearing potential if they have not experienced menarche, are postmenopausal (defined as having no menses for at least 12 months without an alternative medical cause), or are permanently sterile due to total hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
18. Known hypersensitivity to UX701 or its excipients, copper chelators (ie, penicillamine, trientine), zinc or oral corticosteroids that, in the Investigator's judgment, places the subject at increased risk for adverse effects.
19. Participation in another gene transfer study or use of another gene transfer product before or during study participation.
20. Use of any investigational therapy within 30 days prior to Screening (or other duration at the discretion of the Investigator in consultation with the Ultragenyx Medical Director) or during study participation.
21. History of illicit drug use within 60 days prior to Screening or positive results from a urine drug screen during the Screening Period, not including medications prescribed for a diagnosed medical condition or use of cannabinoids for recreational or medicinal purposes.
22. Subjects with known hypersensitivity to amide-containing local anesthetics are excluded from participating in the optional liver biopsy substudy.