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

NCT06650319 | Recruiting Early Phase 1

• 1 other identifier: LY-M003-WD-IIT-002
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Wilson's disease (WD), also known as Wilson's disease, is a rare autosomal recessive metabolic disorder caused by a mutation of the copper transport ATPase β (ATP7B) gene located on the long arm of chromosome 13 (13q14.3). This leads to accumulation of copper ions in multiple organs such as liver, brain and kidney, resulting in organ involvement. In this study, LY-M003 Injection is a gene therapy products with rAAV8 vector. After a single intravenous infusion, LY-M003 can be transduced to the target organ of liver and express the ATP7B in hepatocytese.

Conditions

Wilson Disease

Keywords

Gene therapy

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs) and serious adverse events (SAEs) within 52 weeks after the injection of LY-M003

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

  From enrollment to 52 weeks after administration

• Incidence of dose-limiting toxicity (DLT) events assessed within at least 28 days following LY-M003 infusion

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.The adverse events defined as dose-limiting toxicity (DLT) have been clearly specified in the protocol.

  From enrollment to 52 weeks after administration

Secondary Outcomes (12)

• Percentage decrease in standard of care (SoC) medication use within 52 weeks after administration

  From enrollment to 52 weeks after administration

• Number and proportion of subjects who discontinue standard of care medication within 52 weeks after administration

  From enrollment to 52 weeks after administration

• Change from baseline in serum ceruloplasmin content level through 52 weeks after administration

  From enrollment to 52 weeks after administration

• Change from baseline in total serum copper level through 52 weeks after administrationfrom

  From enrollment to 52 weeks after administration

• Change from baseline in serum non-ceruloplasmin-bound copper (NCC) through 52 weeks after administration

  From enrollment to 52 weeks after administration

Study Arms (5)

LY-M003 Dose group 1-Adult Cohort

EXPERIMENTAL

Adult participants receive a single, peripheral intravenous (IV) infusion of LY-M003 at dose group 1.

Genetic: LY-M003

LY-M003 Dose group 2-Adult Cohort

EXPERIMENTAL

Adult participants receive a single, peripheral intravenous (IV) infusion of LY-M003 at dose group 2.

Genetic: LY-M003

LY-M003 Dose group 3-Adult Cohort

EXPERIMENTAL

Adult participants receive a single, peripheral intravenous (IV) infusion of LY-M003 at dose group 3.

Genetic: LY-M003

LY-M003 Dose group 4-Adult Cohort

EXPERIMENTAL

Adult participants receive a single, peripheral intravenous (IV) infusion of LY-M003 at dose group 4.

Genetic: LY-M003

LY-M003-Pediatric Cohort

EXPERIMENTAL

Based on the accumulated efficacy and safety data of enrolled adult subjects, the investigator and collaborators will determine the starting dose, subsequent enrollment doses for pediatric participants.

Genetic: LY-M003

Interventions

LY-M003 GENETIC

A single peripheral intravenous (IV) infusion of LY-M003

LY-M003 Dose group 1-Adult Cohort; LY-M003 Dose group 2-Adult Cohort; LY-M003 Dose group 3-Adult Cohort; LY-M003 Dose group 4-Adult Cohort; LY-M003-Pediatric Cohort

Eligibility Criteria

• Age: 10 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).
• Patients diagnosed with Wilson Disease .
• Wilson Disease (WD) patients confirmed by laboratory tests to have biallelic mutations in the ATP7B gene.
• 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.
• 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.
• Subjects must be willing to refrain from donating blood, organs, tissues or cells during study participation.
• Negative pregnancy test in women of childbearing potential (WOCBP).
• 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.

You may not qualify if:

• AAV8 neutralizing antibody titer \> 1:10 .
• Active gastrointestinal bleeding within the past 3 months.
• Decompensated cirrhosis or advanced hepatic disease, manifested as portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy, etc.
• 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
• Subjects considered as complicated with severe hypersplenism and requiring splenectomy as judged by the investigator.
• Model for End-Stage Liver Disease (MELD) Score \> 13.
• Other disorders of copper metabolism, such as chronic cholestatic liver diseases, disorders of glycosylation, copper metabolism disorders, etc.
• History of noncompliance with copper chelators or zinc agents within 6 months prior to screening, as determined by the investigator.
• Subjects with treatment-experienced WD who have ALT and/or AST 5 times greater than the upper limit of normal (ULN).
• Severe central nervous system symptoms urgent for intensive hospitalization judged by the investigator.
• Hemoglobin \< 90 g/L.
• A history of epileptic seizures or other diseases that may potentially affect compliance with study procedures within 6 months prior to the screening period.
• Hepatitis B surface antigen (HBsAg) positive, hepatitis C virus (HCV) antibody positive, human immunodeficiency virus (HIV) antibody positive or Treponema pallidum antibody positive.
• Subjects with end-stage renal disease receiving dialysis (chronic kidney disease stage 3 and above) or creatinine clearance \< 60 mL/min.
• Severe hyperlipidemia (triglycerides \> 1000 mg/dL).

Sponsors & Collaborators

• Chaohui Yu: lead

Study Sites (1)

First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 312000, China

RECRUITING

MeSH Terms

Conditions

Hepatolenticular Degeneration

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Chaohui Yu, PhD

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chaohui Yu, PhD

CONTACT

86+13957161659; ych623@sina.com

Yi Chen, PhD

CONTACT

86+13735536389; yiiic@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 21, 2024
• Study Start: September 24, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): March 30, 2030
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)