The Safety, Tolerability and Efficacy of Multiple Subcutaneous Injections of SHR-1209 in Subjects With Hyperlipidemia

Study Overview
=================
Brief Summary
-----------------
This is a randomized, double-blind, placebo- controlled phaseⅠb/Ⅱclinical study. Totally 108 subjects are planned to enrolled with 36 subjects in three low-dose groups (group 1, group 2 and group 3) and 72 subjects in three high-dose groups (group 4, group 5, and group 6).12 subjects with hyperlipidemia who received statin stable treatment for more than 28 days are enrolled in each low-dose group, randomly given SHR-1209 or placebo treatment at a ratio of 5:1. 24 subjects with hyperlipidemia who received statin stable treatment for more than 28 days are enrolled in each high-dose group, randomly given SHR-1209 or placebo treatment at a ratio of 5:1. The primary objective of this study is to evaluate the safety, tolerability, and efficacy of multiple subcutaneous injections of SHR-1209 in hyperlipidemia subjects treated with stabilized dose of statin. Groups detail as follows: SHR-1209 dose 1 /placebo frequence 1 SHR-1209 dose 2 /placebo frequence 2 SHR-1209 dose 3 /placebo frequence 3 SHR-1209 dose 4 /placebo frequence 1 SHR-1209 dose 5 /placebo frequence 2 SHR-1209 dose 6 /placebo frequence 3

Official Title
-----------------
The Safety, Tolerability and Efficacy of Multiple Subcutaneous Injections of SHR-1209 in Subjects With Hyperlipidemia - A PhaseⅠb/Ⅱ Randomized, Double-Blind, Placebo-Controlled Clinical Study

Conditions
-----------------
Hyperlipidemia

Intervention / Treatment
-----------------
* Drug: SHR-1209
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 and ≤65 years old; Subjects who are receiving statin therapy at the time of screening or who are eligible for statin therapy can randomized to receive a stable dose of statin therapy for more than 28 days and are willing to maintain stable statin therapy in this study; Low-density lipoprotein cholesterol (LDL-C) level ≥2.6mmol/L of subjects who receiving statin and/or other lipid-lowering therapy at the time of screening, or LDL-C≥ 3.4mmol/L of subjects who didn't receive any-lowering therapy at the time of screening, and LDL-C still ≥2.6mmol/L before randomization; Fasting triglycerides ≤4.5 mmol/L; Body mass index (BMI) ≥18 and ≤ 35 kg/m2; Signed informed consent. Exclusion Criteria: A clinical history of drug allergy or a history of atopic allergic diseases (asthma, urticaria, eczema dermatitis) or a known allergy to experimental or similar experimental drugs; Diagnosis of homozygous familial hypercholesterolemia; New York heart association (NYHA) defined Ⅱ - Ⅳ history of heart failure; History of acute coronary syndrome (e.g. myocardial infarction, hospitalization for unstable angina), or percutaneous coronary intervention, or coronary artery bypass graft, or history of cerebrovascular disease, within 12 months prior to screening; Uncontrolled severe arrhythmias that are not controlled by drugs or other therapy within 12 months prior to enrollment; Uncontrolled hypertension (systolic blood pressure ≥ 160 and/or diastolic blood pressure ≥ 100 mmHg); Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or gamma pancreatic acyl transferase (GGT), more than 2.5x ULN; Subjects with previous malignant tumor diseases. etc.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1209<br>Participants received one of 6 dose levels of SHR-1209 administered as multiple subcutaneous doses. | Drug: SHR-1209<br>* Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous<br>|
| Placebo Comparator: Placebo<br>Participants received matching placebo dose regimens by subcutaneous injection. | Drug: Placebo<br>* Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary efficacy end point:Percent change from baseline to end of the dosing interval in LDL-C. |  | Baseline to day 113 for group1,2,4,5 or day 169 for group 3,6 | 
| Primary safety end point:Number of subjects with adverse events. |  | Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline to end of the dosing interval in LDL-C. |  | Baseline to day 113 for group1,2,4,5 or day 169 for group 3,6 | 
| Percent change from baseline to day 85 in LDL-C. |  | Baseline to day 85 for all 6 groups | 
| Absolute change from baseline to day 85 in LDL-C. |  | Baseline to day 85 for all 6 groups | 
| Percent change in PCSK9. |  | Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5 | 
| Absolute change in PCSK9. |  | Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5 |