A study to understand the safety and the effects of a virus that transfers a modified protein responsible for copper metabolism (copper-transporting P-type adenosine triphosphatase, ATP7B) in adults with Wilson disease.
- Conditions
- Wilson diseaseMedDRA version: 20.0Level: LLTClassification code: 10047988Term: Wilson's disease Class: 10010331Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- CTIS2022-502873-40-00
- Lead Sponsor
- ltragenyx Pharmaceutical Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 87
Individuals = 18 years of age at the time of informed consent., Confirmed diagnosis of Wilson disease based on genetic confirmation of heterozygous or homozygous biallelic ATP7B mutation., 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 (defined as 2 values within 30% at 2 time points approximately 4 weeks apart)., Ongoing restriction of high copper containing foods for at least 12 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 longterm follow-up.
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 12 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: - Stage 1 only: ALT or AST > 2.5 ULN - Stage 2 only: 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 m^2 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 healthcare professional before enrolling into the study - Columbia Suicide Severity Rating Scale (C-SSRS) assessment with a Yes response to Question 4 or Question 5 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 (Hallucination), Question 15 (Unusual Thought Content), and Question 16 (Blunt Affect) - 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, 12. History or presence of hepatitis B virus infection as defined by the laboratory assessment criteria 13. History or presence of hepatitis C virus infection as defined by the laboratory assessment criteria 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) at any time during the study 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 childbearin
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method