Efficacy and Safety of JS002 as Monotherapy in Patients With Primary Hypercholesterolaemia and Mixed Dyslipidemia

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, safety, PK/PD profile, immunogenicity as well as complete delivery of auto-injector by patients of JS002 as monotherapy in patients with primary hypercholesterolaemia and mixed dyslipidemia. In this study, two dose cohorts(150 mg, 450 mg) are set up, and 582 subjects are planned to be enrolled (randomizedly assigned to JS002 or placebo 150/450 mg group in a 2:1:2:1 ratio).A screening period (≤6 weeks), a double-blind treatment period (12 weeks), an open-label treatment period (40 weeks), and a follow-up period (8 weeks) will be required.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Efficacy and Safety of JS002 as Monotherapy in Patients With Primary Hypercholesterolaemia and Mixed Dyslipidemia

Conditions
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Primary Hypercholesterolaemia and Mixed Dyslipidemia

Intervention / Treatment
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* Drug: JS002
* Drug: JS002
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age 18 80 years old Subject who has not achieve LDL-C goal as categorized by their CV risk at screening Fasting TG≤4.5mmol/L by central laboratory at screening Statin intolerance subject must have a history of statin intolerance as evidenced Exclusion Criteria: History of hemorrhagic stroke NYHA III or IV heart failure, or known LVEF< 30% within 1 year before randomization Uncontrolled serious cardiac arrhythmia defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, within 90 days prior to randomization Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke, deep vein thrombosis or pulmonary embolism within 90 days prior to randomization Planned cardiac surgery or revascularization Uncontrolled hypertension defined as sitting systolic blood pressure(SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg Type 1 diabetes, poorly controlled type 2 diabetes (HbA1c > 8%), newly diagnosed type 2 diabetes (within 90 days of randomization) Others factors not suitable for participation judged by PI

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JS002 150mg Q2W<br>JS002 150mg Q2W SC for 52 weeks | Drug: JS002<br>* JS002 will be administered per auto-injector. Participants will receive JS002 every 2 weeks subcutaneously.<br>|
| Placebo Comparator: JS002 450mg Q4W<br>JS002 450mg Q4W SC for 52 weeks | Drug: JS002<br>* JS002 will be administered per auto-injector. Participants will receive JS002 every 4 weeks subcutaneously.<br>|
| Placebo Comparator: Placebo Q2W<br>Placebo Q2W SC for 12 weeks, then switch to JS002 150mg Q2W SC for 40 weeks | Drug: Placebo<br>* Placebo will be administered per auto-injector. Participants will receive placebo every 2 weeks subcutaneously.<br>|
| Placebo Comparator: Placebo Q4W<br>Placebo Q4W SC for 12 weeks, then switch to JS002 450mg Q4W SC for 40 weeks | Drug: Placebo<br>* Placebo will be administered per auto-injector. Participants will receive placebo every 4 weeks subcutaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in LDL-C at Week 12 | Percent Change From Baseline in LDL-C at Week 12 in statin intolerance subjects | Baseline and week 12 | 
| Percent Change From Baseline in LDL-C at Week 12 | Percent Change From Baseline in LDL-C at Week 12 in ITT subjects | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in LDL-C at Week 12 | Change From Baseline in LDL-C at Week 12 in statin intolerance and ITT subjects | Baseline and week 12 | 
| Percent Change From Baseline in LDL-C at Week 24,52 | Percent Change From Baseline in LDL-C at Week 24,52 in statin intolerance and ITT subjects | Baseline and week 24,52 | 
| Change From Baseline in LDL-C at Week 24,52 | Change From Baseline in LDL-C at Week 24,52 in statin intolerance and ITT subjects | Baseline and week 24,52 | 
| Percent Change From Baseline in other lipid parameters such as non-HDL-C, ApoB, TC, et al. at Week 12, 24, 52 | Percent Change From Baseline in other lipid parameters at Week 12, 24, 52 in statin intolerance and ITT subjects | Baseline and week 12, 24, 52 | 
| Percentage of Participants With LDL-C Less Than 1.8 mmol/L(70 mg/dL) | Percentage of Participants With LDL-C Less Than 1.8 mmol/L(70 mg/dL) at Week 12, 24, 52 in statin intolerance and ITT subjects | Baseline and week 12, 24, 52 | 
| Percentage of Participants With Full Administration of JS002 | Percentage of Participants With Full Administration of JS002 at Weeks 12, 24, 52 in statin intolerance and ITT subjects | Baseline and week 12, 24, 52 |