A Study to Evaluate the Efficacy and Safety of JS002 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH).

Study Overview
=================
Brief Summary
-----------------
JS002 is a recombinant human anti-PCSK9 monoclonal antibody.The study is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical study in Chinese patients with heterozygous familial hypercholesterolemia (HeFH). Objective To evaluate the efficacy and safety of JS002 150 mg (Q2W) and 450 mg (Q4W) subcutaneous injection (SC).

Detailed Description
-----------------
A randomized, double-blind, placebo-controlled Phase III clinical study evaluating the efficacy and safety of JS002 in patients with heterozygous familial hypercholesterolemia. 120 subjects are planned to be enrolled. Each subject is required a maximum of 6 weeks of screening, 24 weeks of treatment, and 8 weeks of follow-up. To evaluate the lipid-lowering efficacy of subcutaneous injection of JS002 at 24 weeks compared with placebo in heterozygous familial hypercholesterolemia patients under optimized lipid lowing therapy . Subjects meeting the study inclusion criteria will be randomly assigned in a 2:1:2:1 ratio to JS002 150 mg Q2W or JS002 450 mg Q4W or matched placebo to receive the study drug (JS002) or placebo subcutaneously for 24 weeks. treatment cohorts: JS002 150mg Cohort:JS002 150mg or placebo treatment(JS002 :Placebo=2:1) Q2W JS002 450mg Cohort:JS002 450mg or placebo treatment(JS002 :Placebo=2:1)Q4W

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of Recombinant Humanized Anti-PCSK9 Monoclonal Antibody Injection in Subjects With Heterozygous Familial Hypercholesterolemia

Conditions
-----------------
Heterozygous Familial Hypercholesterolemia

Intervention / Treatment
-----------------
* Biological: Ongericimab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent. Males and females ≥ 18 to ≤ 80 years of age DLCN>8 in HeFH Stable lipid-lowering therapies for at least 4 weeks Patients with ASCVD LDL cholesterol≥1.4mmol/L at screening Patients without ASCVD LDL cholesterol≥2.6mmol/L at screening Triglyceride≤4.5 mmol/L（400 mg/dL）; Exclusion Criteria: HoFH or meet the diagnostic criteria of HoFH New York Heart Association (NYHA) class III or IV or last known left ventricular ejection fraction < 30% History of uncontrolled arrhythmia within 90 days Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 90 days of randomization Planned cardiac surgery or revascularization. Uncontrolled diabetes mellitius (HbA1c>8.0%）. Uncontrolled hypertension. Other conditions that the researchers considered inappropriate to participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: JS002 150mg Q2W for 24 weeks<br>40 patients will be enrolled in this arm | Biological: Ongericimab<br>* Administered by subcutaneous injection<br>* Other names: JS002;|
| Placebo Comparator: placebo 150mg Q2W for 24 weeks<br>20 patients will be enrolled in this arm | Drug: Placebo<br>* Administered by subcutaneous injection<br>|
| Experimental: JS002 450mg Q4W for 24 weeks<br>40 patients will be enrolled in this arm | Biological: Ongericimab<br>* Administered by subcutaneous injection<br>* Other names: JS002;|
| Placebo Comparator: placebo 450mg Q4W for 24 weeks<br>20 patients will be enrolled in this arm | Drug: Placebo<br>* Administered by subcutaneous injection<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 | LDL-C was quantified using the enzymatic colorimetric assay | Baseline and week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 | LDL-C was quantified using the enzymatic colorimetric assay | Baseline and Week 24 | 
| Percentage changes From Baseline in the Total Cholesterol at week 24 | TC was quantified using the enzymatic colorimetric assay | Baseline and Week 24 | 
| Absolute changes From Baseline in the Total Cholesterol at week 24 | TC was quantified using the enzymatic colorimetric assay | Baseline and Week 24 | 
| Percentage changes From Baseline in Non-HDL-C at Week 24 | Non-HDL-C was quantified using the Calculation,TC minus HDL-C | Baseline and Week 24 | 
| Absolute changes From Baseline in Non-HDL-C at Week 24 | Non-HDL-C was quantified using the Calculation,TC minus HDL-C | Baseline and Week 24 | 
| Percentage changes From Baseline in Apo B at Week 24 | Apo B was quantified using the turbidimetric immunoassay(TIA) | Baseline and Week 24 | 
| Absolute changes From Baseline in Apo B at Week 24 | Apo B was quantified using the turbidimetric immunoassay(TIA) | Baseline and Week 24 | 
| Percentage changes From Baseline in Lp(a) at Week 24 | Lp(a) was quantified using the turbidimetric immunoassay(TIA) | Baseline and Week 24 | 
| Absolute changes From Baseline in Lp(a) at Week 24 | Lp(a) was quantified using the turbidimetric immunoassay(TIA) | Baseline and Week 24 | 
| Percentage changes From Baseline in HDL-C at Week 24 | HDL-C was quantified using the enzymatic colorimetric assay | Baseline and Week 24 | 
| Absolute changes From Baseline in HDL-C at Week 24 | HDL-C was quantified using the enzymatic colorimetric assay | Baseline and Week 24 | 
| Percentage changes From Baseline in Apo A1 at Week 24 | Apo A1 was quantified using the turbidimetric immunoassay(TIA) | Baseline and Week 24 | 
| Absolute changes From Baseline in Apo A1 at Week 24 | Apo A1 was quantified using the turbidimetric immunoassay(TIA) | Baseline and Week 24 | 
| Percentage changes From Baseline in TG at Week 24 | TG was quantified using the enzymatic colorimetric assay | Baseline and Week 24 | 
| Absolute changes From Baseline in TG at Week 24 | TG was quantified using the enzymatic colorimetric assay | Baseline and Week 24 | 
| The ratio of TC/HDL - C | Calculation | Baseline and Week 24 | 
| The ratio of Apo B/Apo A1 | Calculation | Baseline and Week 24 | 
| Percentage of Participants With 50% or Greater Reduction in LDL-C From Baseline at Week 24 | Calculation | Baseline and Week 24 |