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

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

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.

Inclusion Criteria:

1. Signed informed consent
2. Age 18~80 years old
3. Subject who has not achieve LDL-C goal as categorized by their CV risk at screening
4. Fasting TG≤4.5mmol/L by central laboratory at screening
5. Statin intolerance subject must have a history of statin intolerance as evidenced

Exclusion Criteria:

1. History of hemorrhagic stroke
2. NYHA III or IV heart failure, or known LVEF< 30% within 1 year before randomization
3. 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
4. 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
5. Planned cardiac surgery or revascularization
6. Uncontrolled hypertension defined as sitting systolic blood pressure(SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg
7. Type 1 diabetes, poorly controlled type 2 diabetes (HbA1c > 8%), newly diagnosed type 2 diabetes (within 90 days of randomization)
8. Others factors not suitable for participation judged by PI