A Clinical Study to Evaluate the Safety and Efficacy of LY-M003 Injection in Patients With Wilson Disease

Exclusion Criteria

• •1. AAV8 neutralizing antibody titer \> 1:10 .
• •2. Active gastrointestinal bleeding within the past 3 months.
• •3. Decompensated cirrhosis or advanced hepatic disease, manifested as portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy, etc.
• •4. Subjects with other liver diseases as determined by the investigator, such as immune hepatitis, alcoholic liver disease, primary biliary cholangitis, primary sclerosing cholangitis, and/or drug or toxic liver disease
• •5. Subjects considered as complicated with severe hypersplenism and requiring splenectomy as judged by the investigator.
• •6. Model for End-Stage Liver Disease (MELD) Score \> 13.
• •7. Other disorders of copper metabolism, such as chronic cholestatic liver diseases, disorders of glycosylation, copper metabolism disorders, etc.
• •8. History of noncompliance with copper chelators or zinc agents within 6 months prior to screening, as determined by the investigator.
• •9. Subjects with treatment-experienced WD who have ALT and/or AST 5 times greater than the upper limit of normal (ULN).
• •10. Severe central nervous system symptoms urgent for intensive hospitalization judged by the investigator.
• •11. Hemoglobin \< 90 g/L.
• •12. A history of epileptic seizures or other diseases that may potentially affect compliance with study procedures within 6 months prior to the screening period.
• •13. Hepatitis B surface antigen (HBsAg) positive, hepatitis C virus (HCV) antibody positive, human immunodeficiency virus (HIV) antibody positive or Treponema pallidum antibody positive.
• •14. Subjects with end-stage renal disease receiving dialysis (chronic kidney disease stage 3 and above) or creatinine clearance \< 60 mL/min.
• •15. Severe hyperlipidemia (triglycerides \> 1000 mg/dL).
• •16. Subject received or plans to receive bone marrow transplantation, hematopoietic stem cell transplantation and/or major organ transplantation, including but not limited to liver transplantation, kidney transplantation, etc.
• •17. Clinically diagnosed or judged as serious cardiovascular disease by the investigator (eg, classification of heart failure ≥ 3 according to New York Heart Association \[NYHA\]).
• •18. Patients with uncontrolled concomitant diseases or infectious diseases as judged by the investigator.
• •19. Subjects who have hypersensitivity to any component of LY-M003 injection.
• •20. Subjects who have previously received gene therapy or cell therapy of any kind.
• •21. Subjects who use systemic immunosuppressive agents or receive steroid therapy within 3 months prior to dosing (except for prophylactic immunosuppressive therapy as specified in protocol).
• •22. Subjects with history of cancer within 5 years prior to screening, except for completely resected non-melanoma skin cancer, non-metastatic prostate cancer and completely cured ductal carcinoma in situ.
• •23. Subjects who have vaccinated with attenuated live vaccine within 4 months prior to screening or plan to receive a live attenuated vaccine during the clinical trial.
• •24. Subjects who have received treatment or disposition with another investigational drug or investigational device within 28 days or 5 half-lives (drug only), whichever is longer, prior to screening.
• •25. Pregnant women (or women planning to become pregnant) or lactating women.
• •26. Other circumstances in which the investigator deems the subject inappropriate for study participation.