Phase I/II Clinical Study to Evaluate the Safety, Tolerability and Efficacy of LY-M003 Injection in Adult Patients With Wilson's Disease

NCT07641140 | Not Yet Recruiting Phase 1

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

Brief Summary

This is a multicenter, open-label, single-arm, single-dose Phase I/II clinical study. It aims to evaluate the safety, tolerability, efficacy, immunogenicity, pharmacodynamic (PD) and pharmacokinetic (PK) profiles of LY-M003 Injection in patients with Wilson's Disease (WD).

Conditions

Wilson's Disease

Keywords

Wilson's Disease; LY-M003 Injection; Gene Therapy

Outcome Measures

Primary Outcomes (2)

• Phase I:The incidence of dose-limiting toxicity (DLT) events adjudicated by the Safety Review Committee (SRC) within at least 28 days after LY-M003 infusion.

  The incidence of DLT will be assessed using CTCAE 6.0.

  Within 28 days after infusion of LY-M003 Injection

• The incidence of treatment-emergent adverse events (AEs), adverse events of special interest (AESIs) and serious adverse events (SAEs) related to LY-M003 within 52 weeks after infusion.

  Assessment will be conducted via 12-lead ECG, laboratory tests(blood routine, blood biochemistry, coagulation function, stool routine, urine routine), vital signs (blood pressure, pulse, respiratory rate, body temperature) and physical examination.

  5 years

Secondary Outcomes (30)

• Percentage reduction in the dosage of standard of care (SoC) medications within 52 weeks after administration.

  Within 52 weeks after administration

• Number and proportion of subjects who discontinued standard of care (SoC) medications within 52 weeks after administration.

  Within 52 weeks after administration

• Duration (in treatment weeks) of consecutive discontinuation of SoC medications among the above subjects.

  Within 52 weeks after administration

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

  Within 52 weeks after administration

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

  Within 52 weeks after administration

Study Arms (3)

Phase 1: LY-M003 Dose group 1

EXPERIMENTAL

Genetic: LY-M003 Injection

Phase 1: LY-M003 de-escalation dose

EXPERIMENTAL

Genetic: LY-M003 Injection

Phase 2: LY-M003 Dose group 1

EXPERIMENTAL

Genetic: LY-M003 Injection

Interventions

LY-M003 Injection GENETIC

Phase 1: Participants receive a single, peripheral intravenous (IV) infusion of LY-M003 at dose group 1.The dose for Dose Group 1 is 4.0 × 10¹³ vg/kg.All participants are administered the drug once via intravenous injection.

Phase 1: LY-M003 Dose group 1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The subject fully comprehends the purpose, design, methods and possible adverse events of the study, agrees to participate voluntarily and signs the informed consent form (ICF).
• Patients with confirmed diagnosis of Wilson's disease (WD).
• Subjects with Wilson's disease (WD) confirmed by laboratory testing to have biallelic ATP7B gene mutation or deletion.
• The subjects are treated patients with Wilson's disease (WD) who have received standard therapy (e.g., D-penicillamine or zinc acetate) continuously for at least 6 months prior to screening.
• Subjects have maintained a low-copper diet for at least 6 consecutive months prior to screening and will continue this dietary restriction throughout the study.
• Subjects must agree to refrain from donating blood, organs, tissues or cells at any time after treatment.
• Female subjects of childbearing potential (WOCBP) must have a negative pregnancy test.
• Subjects and their partners must have no plans for pregnancy from screening through 6 months after study completion, and will voluntarily use effective contraception (e.g., abstinence, condoms). Subjects shall not plan to donate sperm or ova.

You may not qualify if:

• AAV8 neutralizing antibody titer \> 1:10 .
• History of active gastrointestinal bleeding within the past 3 months.
• Decompensated liver cirrhosis or advanced liver disease presenting with portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy, etc.
• Subjects with other concomitant liver diseases as judged by the investigator, including autoimmune hepatitis, alcoholic liver disease, primary biliary cholangitis, primary sclerosing cholangitis, and/or drug- or toxin-induced liver disease.
• Subjects with severe hypersplenism complicated and requiring splenectomy as assessed 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.
• A history of non-compliance with copper chelators or zinc agents as assessed by the investigator within 6 months prior to screening.
• Previously treated WD subjects with ALT and/or AST levels more than 5 times the upper limit of normal (ULN).
• Subjects with severe neurological deficits or impairments that, in the investigator's judgment, compromise their safety and/or ability to participate in the study.
• Hemoglobin \< 90g/L.
• Subjects with positive hepatitis B surface antigen (HBsAg), positive hepatitis C virus (HCV) antibody, positive human immunodeficiency virus (HIV) antibody or positive treponema pallidum antibody.
• Subjects with end-stage renal disease on dialysis (Chronic Kidney Disease Stage 3 and above), or creatinine clearance \< 60 mL/min.
• Severe hyperlipidemia (triglycerides \>1000 mg/dL);
• Subjects who have received or plan to undergo bone marrow transplantation, hematopoietic stem cell transplantation and/or major organ transplantation, including but not limited to liver transplantation and renal transplantation.

Sponsors & Collaborators

• Lingyi Biotech Co., Ltd.: lead

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

Location

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

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rihong He

CONTACT

+8619121572057; rihong.he@lingyimed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: June 11, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2032
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)