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

Launched by CHAOHUI YU · Oct 18, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called LY-M003 injection for people with Wilson Disease, a rare genetic condition that causes copper to build up in the body, leading to serious health problems. The trial is looking at whether this gene therapy can safely deliver the missing ATP7B protein to the liver, which may help manage the disease. To be eligible, participants must be diagnosed with Wilson Disease, have a specific genetic mutation, and have already tried standard treatments for at least six months. They should also be willing to follow a low-copper diet and not donate blood or organs during the study.

Participants in this trial will receive a single intravenous infusion of the LY-M003 injection and will be monitored for safety and effectiveness. It's important for anyone considering joining the study to know that they will need to meet certain health criteria, such as having no severe liver disease or recent serious health issues. This study aims to provide new hope for those with Wilson Disease, and participants will play a critical role in advancing our understanding of this treatment.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. The subject must be able to fully understood the purpose, nature, method, and possible adverse effects of the study, must be able to voluntarily participate in the study and voluntarily able to provide the written informed consent form (ICF).
• • 2. Subjects with confirmed Wilson Disease: Leipzig scoring system assessment ≥ 4 points.
• • 3. Subjects with confirmed WD bichromosomal ATP7B gene mutation or missing by laboratory testing.
• • 4. 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.
• • 5. 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.
• • 6. Subjects must be willing to refrain from donating blood, organs, tissues or cells during study participation.
• • 7. Negative pregnancy test in women of childbearing potential (WOCBP).
• Exclusion Criteria:
• • 1. AAV8 neutralizing antibody (NAbs) titer positive .
• • 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. Hepatitis B surface antigen (HBsAg) positive, hepatitis C virus (HCV) antibody positive, human immunodeficiency virus (HIV) antibody positive or Treponema pallidum antibody positive.
• • 13. Subjects with end-stage renal disease receiving dialysis (chronic kidney disease stage 3 and above) or creatinine clearance \< 60 mL/min.
• • 14. Severe hyperlipidemia (triglycerides \> 1000 mg/dL).
• • 15. 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.
• • 16. Clinically diagnosed or judged as serious cardiovascular disease by the investigator (eg, classification of heart failure ≥ 3 according to New York Heart Association \[NYHA\]).
• • 17. Subjects who have hypersensitivity to any component of LY-M003 injection.
• • 18. Subjects who have previously received gene therapy or cell therapy of any kind.
• • 19. 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).
• • 20. 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.
• • 21. 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.
• • 22. 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.
• • 23. Pregnant women (or women planning to become pregnant) or lactating women.