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.
This study adopts a prospective, single-center, open, single-arm, single-dose clinical design to evaluate the safety, tolerability, efficacy, immunogenicity, PD and PK characteristics of LY-M003 injection in WD patients, including the main study phase and the long-term follow-up study phase. This study is designed with 4 dose groups and 2 cohorts (adult cohort and pediatric cohort), namely: Dose Group 1 (1.0 × 10¹³ vg/kg), Dose Group 2 (2.0 × 10¹³ vg/kg), Dose Group 3 (4.0 × 10¹³ vg/kg) and Dose Group 4 (6.0 × 10¹³ vg/kg). Among them, Dose Group 1 serves as the starting dose of this study. The decision to escalate to the 4th dose group shall be made by the investigators and collaborators based on the accumulated safety, efficacy and other relevant data. Based on the accumulated efficacy and safety data of enrolled adult subjects, the investigator and collaborators will determine the starting dose, subsequent enrollment doses, and the number of enrolled cases for pediatric subjects.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
A single peripheral intravenous (IV) infusion of LY-M003
First Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, China
RECRUITINGIncidence 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.
Time frame: 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.
Time frame: From enrollment to 52 weeks after administration
Percentage decrease in standard of care (SoC) medication use within 52 weeks after administration
To assess the reduction in standard of care (SoC) medication use in subjects who completed administration of LY-M003 injection.
Time frame: From enrollment to 52 weeks after administration
Number and proportion of subjects who discontinue standard of care medication within 52 weeks after administration
To evaluate the number and proportion of subjects who complete the administration of LY-M003 injection and discontinued standard of care (SOC) drugs.
Time frame: From enrollment to 52 weeks after administration
Change from baseline in serum ceruloplasmin content level through 52 weeks after administration
To assess from baseline in serum ceruloplasmin content level through 52 weeks afterinjection of LY-M003.
Time frame: From enrollment to 52 weeks after administration
Change from baseline in total serum copper level through 52 weeks after administrationfrom
To assess change from baseline in total serum copper level through 52 weeks after injection of LY-M003.
Time frame: From enrollment to 52 weeks after administration
Change from baseline in serum non-ceruloplasmin-bound copper (NCC) through 52 weeks after administration
To assess change from baseline in serum non-ceruloplasmin-bound copper (NCC) through 52 weeks after injection of LY-M003.
Time frame: From enrollment to 52 weeks after administration
Change from baseline in 24-hour urinary copper Concentration through 52 weeks after administration
To assess change from baseline in 24-hour urinary copper Concentration through 52 weeks after injection of LY-M003.
Time frame: From enrollment to 52 weeks after administration
Change from baseline in serum ceruloplasmin activity level through 52 weeks after administration
To assess change from baseline in serum ceruloplasmin activity level through 52 weeks after injection of LY-M003.
Time frame: From enrollment to 52 weeks after administration
Assessment of the change from baseline in neurological subscale of the Unified Wilson Disease Rating Scale (UWDRS) through 52 weeks after administration.
Assessment of the score change from baseline via the evaluation of neurological subscale of the Unified Wilson Disease Rating Scale (UWDRS).
Time frame: From enrollment to 52 weeks after administration
Assessment of the change from baseline in hepatic subscale of the Unified Wilson Disease Rating Scale (UWDRS) through 52 weeks after administration
Assessment of the score change from baseline via the evaluation of hepatic subscale of the Unified Wilson Disease Rating Scale (UWDRS).
Time frame: From enrollment to 52 weeks after administration
Assessment of the change from baseline in psychiatric subscale of the Unified Wilson Disease Rating Scale (UWDRS) through 52 weeks after administration
Assessment of the score change from baseline via the evaluation of psychiatric subscale of the Unified Wilson Disease Rating Scale (UWDRS).
Time frame: From enrollment to 52 weeks after administration
Change from baseline in liver elasticity through 52 weeks after administration
Assessment of the change in liver elasticity from baseline in subjects via detection with hepatobiliary color Doppler ultrasound combined with ultrasound elastography.
Time frame: From enrollment to 52 weeks after administration
Change from baseline in Kayser-Fleischer (K-F) rings through 52 weeks after administration
Evaluation of the change in Kayser-Fleischer (K-F) ring grade from baseline via slit-lamp examination of the eye.
Time frame: From enrollment to 52 weeks after administration
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