The Efficacy and Safety of JS002 PFS and AI in Patients With Primary Hypercholesterolemia and Mixed 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 efficacy and safety of JS002 prefilled syringes and prefilled autosyringes in patients with primary hypercholesterolemia and mixed hyperlipidemia when combined with statin therapy. In this study, one dose group (150 mg) were set up in this study. 240 subjects are plan to be enrolled (the study drug will be assigned to a 2:1 :2:1ratio of JS002 PFS / placebo or JS002 AI / placebo ). Each subject required a maximum of 6 weeks of screening, 12 weeks of treatment, and 8 weeks of follow-up.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase III Clinical Study Evaluating the Efficacy and Safety of JS002 Prefilled Syringes(PFS) and Prefilled Autosyringes(AI) in Patients With Primary Hypercholesterolemia and Mixed Hyperlipidemia

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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Inclusion Criteria: Signed informed consent. Age 18 80 years old; Stable optimized LLT at least 4 weeks before randomization; Two times of Fasting triglycerides ≤4.5 mmol/L(400mg/dL)at the time of screening; Exclusion Criteria: History of NYHA class III-IV heart failure or EF<30%; History of uncontrolled arrhythmia within 90 days; History of MI,UA, PCI or CABG, stroke within 90 days; Known hemorrhagic stroke disease; Planned cardiac surgery or revascularization. Uncontrolled hypertension. Uncontrolled diabetes mellitius (HbA1c>8.0%）. Other conditions that the researchers 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>Cobort 1:150 mg/1mL Q2W PFS,Cobort 2:150 mg/1mL Q2W AI | Drug: JS002<br>* JS002:150mg(1mL) Q2W PFS, Placebo: 1mL Q2W PFS.<br>|
| Placebo Comparator: Placebo<br>Cobort 1:/1mL Q2W PFS,Cobort 2:1mL Q2W AI | Drug: Placebo<br>* JS002:150mg(1mL) Q2W AI, Placebo: 1mL Q2W AI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C with JS002 PFS | Percentage change in LDL-C relative to baseline at Week 12 with JS002 PFS | at week 12 | 
| LDL-C with JS002 AI | Percentage change in LDL-C relative to baseline at Week 12 with JS002 AI | at week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C with JS002 PFS | The absolute change in LDL-C relative to baseline with JS002 PFS | at week 12 | 
| LDL-C with JS002 AI | The absolute change in LDL-C relative to baseline with JS002 AI | at week 12 | 
| lipid parameters | Percentages and absolute change in other lipid parameters to baseline with JS002 PFS and JS002 AI | at week 12 | 
| LDL-C reduction≥50 with JS002 PFS | Proportion of subjects with a ≥50% reduction in serum LDL-C at 12 weeks after subcutaneous treatment with JS002 PFS from baseline | at week 12 | 
| LDL-C reduction≥50 with JS002 AI | Proportion of subjects with a ≥50% reduction in serum LDL-C at 12 weeks after subcutaneous treatment with JS002 AI from baseline | at week 12 | 
| LDL-C dropped to < 70 mg/dL with JS002 PFS | Proportion of subjects whose serum LDL-C dropped to < 70 mg/dL (1.8 mmol/L) at 12 weeks after subcutaneous injection of JS002 PFS | at week 12 | 
| LDL-C dropped to < 70 mg/dL with JS002 AI | Proportion of subjects whose serum LDL-C dropped to < 70 mg/dL (1.8 mmol/L) at 12 weeks after subcutaneous injection of JS002 AI | at week 12 | 
| full dose | Proportion of subjects receiving full dose of JS002 AI during treatment (weeks 0, 2, 4, 6, 8, 10) | at week 0, 2, 4, 6, 8, 10 |