Safety and Efficacy of IBI306 in Chinese Subjects With Non-familial Hypercholesterolemia

Study Overview
=================
Brief Summary
-----------------
IBI306 is a fully human monoclonal antibody that binds proprotein convertase substilisin/kexin type 9 (PCSK-9), preventing its interaction with the low-density lipoprotein cholesterol receptor (LDL-R) and thereby restoring LDL-R recycling and low-density lipoprotein cholesterol(LDL-C) uptake. This study is being done to investigate the effects of IBI306 in Chinese people with non-familial hypercholesterolemia with very high or high cardiovascular risk. This study will see if IBI306 will reduce low density lipoprotein cholesterol (LDL-C) in Chinese people who are taking a certain type of lipid-lowering medication (statins with or without ezetimibe) and whether it causes any side effects

Detailed Description
-----------------
This is a phase 3, multicenter, double-blind, randomized, placebo-controlled study of IBI306 in Chinese non-familial hypercholesterolemia Subjects with very high or high cardiovascular risk. A total of around 600 subjects who meet admission criteria will be randomized and receive one of the two dose levels of IBI306 or matching placebo: 450mg Q4W, or 600mg Q6W. The double blind period for both groups will be 48 weeks. The study will last 52 weeks

Official Title
-----------------
Safety and Efficacy of IBI306 in Chinese Non-familial Hypercholesterolemia Subjects at Very High or High Cardiovascular Risk: a Randomized, Double-blind and Placebo-controlled Phase III Study

Conditions
-----------------
Hypercholesterolemia

Intervention / Treatment
-----------------
* Drug: IBI306 450mg SC Q4W
* Drug: Placebo SC Q4W
* Drug: IBI306 600mg SC Q6W
* Other: Placebo SC Q6W


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Males and females ≥ 18 to ≤ 75 years of age Diagnosis of hypercholesterolemia LDL cholesterol ≥ 70 mg/dl (1.8mmol/L) Very high or high cardiovascular risk TG≤500 mg/dL(5.64 mmol/L) Exclusion criteria: Diagnosis of HoFH or HeFH Uncontrolled hypertension Uncontrolled hyperthyroidism or hypothyroidism Severe renal dysfunction Known sensitivity to any of the products to be administered during dosing

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI306 450mg SC Q4W<br> | Drug: IBI306 450mg SC Q4W<br>* Subjects will receive IBI306 450mg every 4 weeks subcutaneously.<br>|
| Placebo Comparator: Placebo SC Q4W<br> | Drug: Placebo SC Q4W<br>* Subjects will receive placebo every 4 weeks subcutaneously.<br>|
| Experimental: IBI306 600mg SC Q6W<br> | Drug: IBI306 600mg SC Q6W<br>* Subjects will receive IBI306 600mg every 6 weeks subcutaneously.<br>|
| Placebo Comparator: Placebo SC Q6W<br> | Other: Placebo SC Q6W<br>* Subjects will receive placebo every 6 weeks subcutaneously.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at week 48 |  | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent of subjects with LDL-C reduction no less than 50% from baseline |  | Week 48 | 
| The percent of subjects with LDL-C<70mg/dL(1.8 mmol/L) |  | Week 48 | 
| The percent change in Lp(a),ApoB, non-HDL-c, ApoB/ApoA1 from baseline |  | Week 48 |