A Multicenter, Open, Single-arm, Single-dose, Phase I/II Study Evaluating the Safety, Tolerability, and Efficacy of LY-M003 Injection in Adult Patients With Wilson's Disease
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 试验地点
- 1
研究概览
简要总结
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).
详细描述
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). The Phase I/II study consists of a main study phase and a long-term follow-up phase. The main study phase includes an 8-week screening period and a 52-week follow-up period after infusion. The long-term follow-up phase starts at Week 53 and lasts until 5 years post-infusion.
The study pre-specified two dose cohorts, consisting of one main dose cohort and one de-escalation dose cohort: Dose Cohort 1 (4.0 × 10¹³ vg/kg) and the de-escalation dose cohort (2.0 × 10¹³ vg/kg). Three subjects will be enrolled in each dose cohort.Dose Cohort 1 serves as the starting dose. After the first subject receives the study drug, a minimum 28-day DLT observation period must be completed to confirm safety before enrolling subsequent subjects.All three subjects in Dose Cohort 1 have completed the 28-day (Day 28) DLT observation period following LY-M003 infusion. The Safety Review Committee (SRC) will make a comprehensive assessment to determine whether to proceed to the dose expansion phase at the dose level of 4.0 × 10¹³ vg/kg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 >
- •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.
- •Subjects with clinically diagnosed severe cardiovascular diseases or those deemed by the investigator to have such conditions (e.g., New York Heart Association [NYHA] heart failure classification ≥ Class 3).
- •Subjects with uncontrolled concomitant diseases or infectious diseases as assessed by the investigator.
- •Subjects who are allergic to any ingredient of LY-M003 Injection.
- •Prior receipt of any type of gene therapy or cell therapy.
- •Use of systemic immunosuppressants or steroids within 3 months prior to administration (except for prophylactic immunosuppressive therapy specified in the protocol).
- •History of cancer within 5 years prior to screening, excluding completely resected non-melanoma skin cancer, non-metastatic prostate cancer and fully cured ductal carcinoma in situ.
- •Received live attenuated vaccines within 4 months prior to screening, or planned to receive such vaccines during the clinical trial.
- •Received treatment or intervention with other investigational drugs or study devices within 28 days or 5 half-lives (for drugs only) prior to screening, whichever is longer.
- •Pregnant women (or women planning pregnancy) or breastfeeding women.
- •Other conditions that, in the investigator's opinion, render the subject ineligible for study participation.
研究组 & 干预措施
Phase 1: LY-M003 Dose group 1
干预措施: LY-M003 Injection (Genetic)
Phase 1: LY-M003 de-escalation dose
干预措施: LY-M003 Injection (Genetic)
Phase 2: LY-M003 Dose group 1
干预措施: LY-M003 Injection (Genetic)