The Safety and Efficacy of Multiple-dose of JS002 in Subject With Hyperlipidemia

Study Overview
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Brief Summary
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JS002 is a recombinant humanized anti-PCSK9 monoclonal antibody. This is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy, as well as immunogenicity of JS002 treated repeatedly in patients with hyperlipidemia when combined with statin therapy. In this study, two dose group (150 mg, 300 mg) were set up in this study. 750 subjects are plan to be enrolled (the study drug will be assigned to a 2:1 ratio of JS002 or placebo). Each subject required a maximum of 6 weeks of screening, 52 weeks of treatment, and 8 weeks of follow-up.

Official Title
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A Phase III, Randomized, Double-blind, Placebo-controlled Clinical Study Evaluating the Efficacy and Safety of JS002 in Patients With Primary Hypercholesterolemia and Mixed Hyperlipidemia in China

Conditions
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Hyperlipemia

Intervention / Treatment
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* Drug: JS002
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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A limited list of criteria for selection of participants in the clinical study, provided in terms of inclusion and exclusion criteria and suitable for assisting potential participants in identifying clinical studies of interest. Use a bulleted list for each criterion below the headers Inclusion Criteria and Exclusion Criteria. (Limit: 15,000 characters.) Inclusion criteria Males and females ≥ 18 and ≤ 80 years of age; LDL_C during screening period met the following conditions: super high risk: LDL - C ≥1.4mmol/L (55 mg/dL); extremely high risk: LDL - C ≥1.8 mmol/L (70 mg/dL); risk: LDL - C ≥2.6 mmol/L (100 mg/dL); low risk: LDL - C ≥ 3.4 /mmol/L (130 mg/dL) Fasting triglycerides ≤4.5 mmol/L; Exclusion criteria Known HoFH; History of NYHA class III-IV heart failure; History of uncontrolled arrhythmia, Unstable angina,MI, PCI,CABG, DVT or pulmonary embolism within 3 months. Uncontrolled hypertension. Uncontrolled diabetes mellitius (HbA1c>8.0%）. Other conditions that investigators considered inappropriate to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JS002<br>Cohort 1: 150 mg/1mL Q2W Subcutaneous(SC); Cohort 2: 300/2mL mg Q4W Subcutaneous(SC); | Drug: JS002<br>* JS002: 150mg(1mL) Q2W; Placebo 1mL Q2W.<br>|
| Placebo Comparator: Placebo<br>Cohort 1: 1mL Q2W Subcutaneous(SC); Cohort 2: 2mL Q4W Subcutaneous(SC); | Drug: Placebo<br>* JS002: 300mg(2mL) Q4W; Placebo 2mL Q4W.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LDL-C of JS002 | Percentage change in LDL-C relative to baseline at Week 24 | Up to 24Weeks after dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LDL-C of JS002 | Percentage change in LDL-C relative to baseline at Week 52 | Up to 52Weeks after dose administration | 
| Other lipid parameters of JS002 | Percentage change in LDL-C relative to baseline at Week 24 and Week 52 | Up to Week 24 and 52Weeks after dose administration | 
| The occurrence of adverse events | Evaluate the change of clinically significant laboratory tests, vital signs, and electrocardiogram | Up 60Weeks after dose administration | 
| The immunogenicity of JS002 | To evaluate the production time, duration and proportion of anti JS002 antibody (ADA).ADA positive samples are tested for titer and for neutralizing antibody (Nab). | Up 60Weeks after dose administration | 
| Pharmacokinetics (PK) of JS002 | Evaluation of Serum concentration of JS002.Descriptive statistics include mean (arithmetic mean and geometric mean), standard deviation (SD), coefficient of variation CV% (arithmetic coefficient and geometric coefficient of variation), Median (Median), minimum (Min) and maximum (Max). | Up 60Weeks after dose administration | 
| Pharmacokinetics (PD) of JS002 | Evaluation of serum concentrations of free/total PCSK9 and changes from baseline.Descriptive statistics include mean (arithmetic mean and geometric mean), standard deviation (SD), coefficient of variation CV% (arithmetic coefficient and geometric coefficient of variation), Median (Median), minimum (Min) and maximum (Max). | Up 60Weeks after dose administration |