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.

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Hypercholesterolaemia and Mixed Dyslipidemia
• Intervention / Treatment: Drug: JS002; Drug: JS002; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 582
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Qiu'e Wan, PM; Phone Number: 86 17710342522; Email: qiu.e_wan@junshipharma.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital
      • Contact: Yida Tang, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JS002 150mg Q2W; JS002 150mg Q2W SC for 52 weeks	Drug: JS002; JS002 will be administered per auto-injector. Participants will receive JS002 every 2 weeks subcutaneously.; Drug: JS002; JS002 will be administered per auto-injector. Participants will receive JS002 every 4 weeks subcutaneously.
Placebo Comparator: JS002 450mg Q4W; JS002 450mg Q4W SC for 52 weeks	Drug: JS002; JS002 will be administered per auto-injector. Participants will receive JS002 every 2 weeks subcutaneously.; Drug: JS002; JS002 will be administered per auto-injector. Participants will receive JS002 every 4 weeks subcutaneously.
Placebo Comparator: Placebo Q2W; Placebo Q2W SC for 12 weeks, then switch to JS002 150mg Q2W SC for 40 weeks	Drug: Placebo; Placebo will be administered per auto-injector. Participants will receive placebo every 2 weeks subcutaneously.; Drug: Placebo; Placebo will be administered per auto-injector. Participants will receive placebo every 4 weeks subcutaneously.
Placebo Comparator: Placebo Q4W; Placebo Q4W SC for 12 weeks, then switch to JS002 450mg Q4W SC for 40 weeks	Drug: Placebo; Placebo will be administered per auto-injector. Participants will receive placebo every 2 weeks subcutaneously.; Drug: Placebo; Placebo will be administered per auto-injector. Participants will receive placebo every 4 weeks subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in LDL-C at Week 12	Percent Change From Baseline in LDL-C at Week 12 in statin intolerance subjects	Baseline and week 12
Percent Change From Baseline in LDL-C at Week 12	Percent Change From Baseline in LDL-C at Week 12 in ITT subjects	Baseline and week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in LDL-C at Week 12	Change From Baseline in LDL-C at Week 12 in statin intolerance and ITT subjects	Baseline and week 12
Percent Change From Baseline in LDL-C at Week 24,52	Percent Change From Baseline in LDL-C at Week 24,52 in statin intolerance and ITT subjects	Baseline and week 24,52
Change From Baseline in LDL-C at Week 24,52	Change From Baseline in LDL-C at Week 24,52 in statin intolerance and ITT subjects	Baseline and week 24,52
Percent Change From Baseline in other lipid parameters such as non-HDL-C, ApoB, TC, et al. at Week 12, 24, 52	Percent Change From Baseline in other lipid parameters at Week 12, 24, 52 in statin intolerance and ITT subjects	Baseline and week 12, 24, 52
Percentage of Participants With LDL-C Less Than 1.8 mmol/L(70 mg/dL)	Percentage of Participants With LDL-C Less Than 1.8 mmol/L(70 mg/dL) at Week 12, 24, 52 in statin intolerance and ITT subjects	Baseline and week 12, 24, 52
Percentage of Participants With Full Administration of JS002	Percentage of Participants With Full Administration of JS002 at Weeks 12, 24, 52 in statin intolerance and ITT subjects	Baseline and week 12, 24, 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with anti-drug antibodies (ADAs)	Serum samples were analyzed for ADA. Positive samples were subsequently tested for neutralizing antibodies.	From baseline to week 60

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 2, 2022
• Primary Completion (Anticipated): October 30, 2023
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: November 14, 2022
• First Posted (Actual): November 17, 2022

Study Record Updates

• Last Update Posted (Actual): November 22, 2022
• Last Update Submitted That Met QC Criteria: November 17, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: JS002-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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