Evaluating LY-M003 Injection for Wilson Disease

Prospective, Single-center, Open-label, Single-arm, Single-dose Clinical Study to Evaluate the Safety, Tolerability and Efficacy of LY-M003 Injection in Adult and Pediatric Patients With Wilson Disease

This study is testing a new gene therapy called LY-M003 to see if it is safe and effective for people with Wilson Disease.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 10 Years to 60 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Zhejiang University (Academic / other)
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06650319 on ClinicalTrials.gov

What this trial studies

This clinical study aims to assess the safety and efficacy of LY-M003, a gene therapy product, in patients diagnosed with Wilson Disease. The study follows a single-center, open-label design where eligible participants will receive a single intravenous infusion of LY-M003. The evaluation includes monitoring safety, tolerability, and the drug's pharmacokinetics and pharmacodynamics over a defined period, followed by long-term follow-up to gather additional data on outcomes. Participants will undergo a series of assessments throughout the study to ensure comprehensive data collection.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals with confirmed Wilson Disease who have previously undergone standard treatment and meet specific genetic criteria.

Not a fit: Patients who have not been treated for Wilson Disease or do not have a confirmed ATP7B gene mutation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a long-term solution for managing Wilson Disease by addressing the underlying genetic cause.

How similar studies have performed: While gene therapy approaches for Wilson Disease are still emerging, similar studies have shown promise in treating genetic disorders, indicating potential for success.

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. Patients diagnosed with Wilson Disease .
3. Wilson Disease (WD) patients confirmed by laboratory tests to have biallelic mutations in the ATP7B gene.
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).
8. 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:

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.

Where this trial is running

Hangzhou, Zhejiang

• First Affiliated Hospital of Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Chaohui Yu, PhD — First Affiliated Hospital of Zhejiang University
• Study coordinator: Chaohui Yu, PhD

Conditions Wilson Disease; Gene therapy