The Safety and Efficacy of Multiple-dose of JS002 in Subject With Hyperlipidemia

A Phase III, Randomized, Double-blind, Placebo-controlled Clinical Study Evaluating the Efficacy and Safety of JS002 in Patients With Primary Hypercholesterolemia and Mixed Hyperlipidemia in China

JS002 is a recombinant humanized anti-PCSK9 monoclonal antibody. This is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy, as well as immunogenicity of JS002 treated repeatedly in patients with hyperlipidemia when combined with statin therapy.

In this study, two dose group (150 mg, 300 mg) were set up in this study. 750 subjects are plan to be enrolled (the study drug will be assigned to a 2:1 ratio of JS002 or placebo).

Each subject required a maximum of 6 weeks of screening, 52 weeks of treatment, and 8 weeks of follow-up.

Study Overview

• Status: Completed
• Conditions: Hyperlipemia
• Intervention / Treatment: Drug: JS002; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 806
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233000
      • The First Affiliated Hospital of Bengbu Medical College
  • Beijing
    • Beijing, Beijing, China, 100000
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100000
      • China-Japan Friendship Hospital
    • Beijing, Beijing, China, 100000
      • Beijing Chaoyang Hospital, Capital Medical University
    • Beijing, Beijing, China, 100000
      • Beijing Anzhen Hospital, Capital Medical University
    • Beijing, Beijing, China, 100000
      • Beijing Tongren Hospital Affiliated to Capital Medical University City:Beijing
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • The Second Affiliated Hospital of Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • The First Affiliated Hospital of Fujian Medical University
    • Fuzhou, Fujian, China, 350000
      • The 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Lanzhou University Second Hospital
    • Lanzhou, Gansu, China, 730000
      • The First Hospital of Lanzhou University City:Lanzhou
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Guangdong General Hospital
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China, 5100000
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    • Shenzhen, Guangdong, China, 518000
      • Peking University Shenzhen Hospital
  • Guangxi
    • Nanning, Guangxi, China, 530000
      • The People's Hospital of Guangxi Zhuang Autonomous Region
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • Affiliated Hospital of Guizhou Medical University
  • Hainan
    • Haikou, Hainan, China, 570100
      • Hainan General Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University
    • Shijiazhuang, Hebei, China, 050000
      • The First Hospital of Hebei Medical University
  • Heilongjiang
    • Daqing, Heilongjiang, China, 163316
      • Daqingshi People's Hospital
    • Haerbin, Heilongjiang, China, 15000
      • The Fourth Affiliated Hospital of Harbin Medical University
  • Henan
    • Luoyang, Henan, China, 471000
      • The First Affiliated Hospital of Henan University of Science And Technology
    • Zhengzhou, Henan, China, 450000
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Jingzhou, Hubei, China, 434000
      • Jingzhou Central Hospital
    • Wuhan, Hubei, China, 430000
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410000
      • The Third Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410100
      • The Second Xiangya Hospital of Central South University
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • The Second People's Hospital of Changzhou
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast Universty
    • Xuzhou, Jiangsu, China, 221000
      • Affiliated Hospital of Xuzhou Medical University
    • Yangzhou, Jiangsu, China, 225000
      • Northern Jiangsu People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330000
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330000
      • The First Hospital of Nanchang
  • Jilin
    • Changchun, Jilin, China, 130000
      • First Hospital of Jilin University
    • Changchun, Jilin, China, 130033
      • China-Japan Union Hospital of Jilin University
  • Liaoning
    • Dalian, Liaoning, China, 116000
      • the central hospital of Dalian
    • Jinzhou, Liaoning, China, 121000
      • The First Affiliated Hospital of Jinzhou Medical University
    • Shenyang, Liaoning, China, 110000
      • The People's Hospital of Liaoning Provincial
    • Shenyang, Liaoning, China, 110020
      • General hospital of the PLA northern theater command
  • Shandong
    • Jinan, Shandong, China, 250000
      • Qilu Hospital of Shandong University
    • Jinan, Shandong, China, 250000
      • Jinan Central Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Shanghai East Hospital
    • Shanghai, Shanghai, China, 200000
      • Huashan Hospital Affiliated to Fudan University
    • Shanghai, Shanghai, China, 200000
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China, 200000
      • Shanghai Changhai Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Shanxi Provincial People's Hospital
    • Taiyuan, Shanxi, China, 030000
      • First Hospital of Shanxi Medical University
    • Xian, Shanxi, China, 710000
      • The First Affiliated Hospital of the Air Force Medical University
    • Xian, Shanxi, China, 710000
      • The Second Affiliated Hospital of Xi'an Jiaotong University
    • Xianyang, Shanxi, China, 712000
      • Xianyang Hospital of Yan 'an University
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • West China Hospital of Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • Tianjin People's Hospital
    • Tianjin, Tianjin, China, 300000
      • Teda International Cardiovascular Hospital
    • Tianjin, Tianjin, China, 300000
      • Tianjin First Central Hospital
  • Zhejiang
    • Taizhou, Zhejiang, China, 318000
      • Taizhou Hospital of Zhejiang Province
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

A limited list of criteria for selection of participants in the clinical study, provided in terms of inclusion and exclusion criteria and suitable for assisting potential participants in identifying clinical studies of interest. Use a bulleted list for each criterion below the headers "Inclusion Criteria" and "Exclusion Criteria". (Limit: 15,000 characters.) Inclusion criteria

1. Males and females ≥ 18 and ≤ 80 years of age;
2. LDL_C during screening period met the following conditions: super high risk: LDL - C ≥1.4mmol/L (55 mg/dL); extremely high risk: LDL - C ≥1.8 mmol/L (70 mg/dL); risk: LDL - C ≥2.6 mmol/L (100 mg/dL); low risk: LDL - C ≥ 3.4 /mmol/L (130 mg/dL)
3. Fasting triglycerides ≤4.5 mmol/L;

Exclusion criteria

1. Known HoFH;
2. History of NYHA class III-IV heart failure;
3. History of uncontrolled arrhythmia, Unstable angina,MI, PCI,CABG, DVT or pulmonary embolism within 3 months.
4. Uncontrolled hypertension.
5. Uncontrolled diabetes mellitius (HbA1c>8.0%）.
6. Other conditions that investigators considered inappropriate to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JS002; Cohort 1: 150 mg/1mL Q2W Subcutaneous(SC); Cohort 2: 300/2mL mg Q4W Subcutaneous(SC);	Drug: JS002; JS002: 150mg(1mL) Q2W; Placebo 1mL Q2W.
Placebo Comparator: Placebo; Cohort 1: 1mL Q2W Subcutaneous(SC); Cohort 2: 2mL Q4W Subcutaneous(SC);	Drug: Placebo; JS002: 300mg(2mL) Q4W; Placebo 2mL Q4W.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LDL-C of JS002	Percentage change in LDL-C relative to baseline at Week 24	Up to 24Weeks after dose administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LDL-C of JS002	Percentage change in LDL-C relative to baseline at Week 52	Up to 52Weeks after dose administration
Other lipid parameters of JS002	Percentage change in LDL-C relative to baseline at Week 24 and Week 52	Up to Week 24 and 52Weeks after dose administration
The occurrence of adverse events	Evaluate the change of clinically significant laboratory tests, vital signs, and electrocardiogram	Up 60Weeks after dose administration
The immunogenicity of JS002	To evaluate the production time, duration and proportion of anti JS002 antibody (ADA).ADA positive samples are tested for titer and for neutralizing antibody (Nab).	Up 60Weeks after dose administration
Pharmacokinetics (PK) of JS002	Evaluation of Serum concentration of JS002.Descriptive statistics include mean (arithmetic mean and geometric mean), standard deviation (SD), coefficient of variation CV% (arithmetic coefficient and geometric coefficient of variation), Median (Median), minimum (Min) and maximum (Max).	Up 60Weeks after dose administration
Pharmacokinetics (PD) of JS002	Evaluation of serum concentrations of free/total PCSK9 and changes from baseline.Descriptive statistics include mean (arithmetic mean and geometric mean), standard deviation (SD), coefficient of variation CV% (arithmetic coefficient and geometric coefficient of variation), Median (Median), minimum (Min) and maximum (Max).	Up 60Weeks after dose administration

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.
• Investigators: Principal Investigator: Yaling Han, Doctor of Medicine, General hospital of the PLA northern theater command

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2020
• Primary Completion (Actual): May 25, 2022
• Study Completion (Actual): January 16, 2023

Study Registration Dates

• First Submitted: February 24, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias
• Other Study ID Numbers: JS002-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No