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

Phase 3

Not yet recruiting

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
JS002 450mg Q4W	JS002	JS002 450mg Q4W SC for 52 weeks
JS002 150mg Q2W	JS002	JS002 150mg Q2W SC for 52 weeks
Placebo Q2W	Placebo	Placebo Q2W SC for 12 weeks, then switch to JS002 150mg Q2W SC for 40 weeks
Placebo Q4W	Placebo	Placebo Q4W SC for 12 weeks, then switch to JS002 450mg Q4W SC for 40 weeks

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in LDL-C at Week 12	Baseline and week 12	Percent Change From Baseline in LDL-C at Week 12 in ITT subjects

Secondary Outcome Measures

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