Wilson's disease (WD)
Conditions
Interventions
Experimental,LY-M003 Dose group 4-Adult Cohort:LY-M003 intravenous injection
Experimental,LY-M003-Pediatric Cohort:LY-M003 intravenous injection
Experimental,LY-M003 Dose group 1-Adult Cohort:LY-M003 intravenous injection
Experimental,LY-M003 Dose group 2-Adult Cohort:LY-M003 intravenous injection
Experimental,LY-M003 Dose group 3-Adult Cohort:LY-M003 intravenous injection
Sponsors
The FIrst Affiliated Hospital, College of Medicine, Zhejiang University
Eligibility
Sex/Gender
All
Age
10 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. Age >=10 years old and =60 years old, gender is not limited. 2. Subjects fully understand the purpose, nature, method and possible adverse reactions of the study, and voluntarily sign an informed consent form (ICF) as subjects. 3. Patients diagnosed with Wilson Disease. 4. Wilson Disease (WD) patients confirmed by laboratory tests to have biallelic mutations in the ATP7B gene. 5. Subjects must be treatment-experienced to WD who have received standard treatment (eg, D-penicillamine or zinc acetate) for at least 6 months prior to the screening period. 6. Subjects must restrict food with high copper content for at least 6 months prior to screening and continue this restriction during the entire duration of study participation. 7. Subjects must be willing to refrain from donating blood, organs, tissues or cells during study participation. 8. Negative pregnancy test in women of childbearing potential (WOCBP). 9. Subjects and their partners who have no childbearing plans from the screening period to 6 months after the end of the study and are willing to adopt effective contraceptive measures (e.g., abstinence, condoms, etc.); subjects have no plans to donate sperm or ova.
Exclusion criteria
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of adverse events (AE) and serious adverse events (SAE) within 52 weeks following LY-M003 infusion.;The incidence of dose-limiting toxicity (DLT) events assessed within at least 28 days following LY-M003 infusion.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in liver elasticity through 52 weeks after administration;Change from baseline in Kayser-Fleischer (K-F) rings through 52 weeks after administration.;The occurrence of abnormalities in cardiac function , vital signs, laboratory test parameters,and physical examination findings within 52 weeks after administration.;Change in serum ceruloplasmin activity levels from baseline within 52 weeks after administration.;Change from baseline in serum ceruloplasmin content level through 52 weeks after administration.;Change from baseline in total serum copper level through 52 weeks after administration.;Change from baseline in serum non-ceruloplasmin-bound copper (NCC) through 52 weeks after administration.;Change from baseline in 24-hour urinary copper Concentration through 52 weeks after administration;Percentage decrease in standard of care (SoC) medication use within 52 weeks after administration.;Number and proportion of subjects who discontinue standard of care medication within 52 weeks after administration.;The number of consecutive treatment weeks with SOC drugs discontinued in the above subjects.;Evaluate the change from baseline in the total score of the first section (neurological subscale) of the Unified Wilson Disease Rating Scale (UWDRS) quantitative score within 52 weeks after admi;Evaluate the change from baseline in the total score of the second section (Hepatic Scale) of the UWDRS quantitative score within 52 weeks after administration.;Evaluate the change from baseline in the total score of the third section (psychiatric subscale) of the UWDRS quantitative score within 52 weeks after administration.;Evaluate the changes from baseline in the scores of individual items/subscales (Speech, Writing, Standing and Gait) of the UWDRS quantitative score within 52 weeks after administration.; | — |
Countries
China
Contacts
Public ContactZhaohui Yu
The FIrst Affiliated Hospital, College of Medicine, Zhejiang University
Outcome results
None listed