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

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

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).

Study Overview

• Status: Completed
• Conditions: Heterozygous Familial Hypercholesterolemia
• Intervention / Treatment: Drug: Placebo; Biological: Ongericimab

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

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100020
      • Beijing Anzhen Hospital Capital Medical University City:Beijing

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent.
2. Males and females ≥ 18 to ≤ 80 years of age
3. DLCN>8 in HeFH
4. Stable lipid-lowering therapies for at least 4 weeks
5. Patients with ASCVD LDL cholesterol≥1.4mmol/L at screening Patients without ASCVD LDL cholesterol≥2.6mmol/L at screening
6. Triglyceride≤4.5 mmol/L（400 mg/dL）;

Exclusion Criteria:

1. HoFH or meet the diagnostic criteria of HoFH
2. New York Heart Association (NYHA) class III or IV or last known left ventricular ejection fraction < 30%
3. History of uncontrolled arrhythmia within 90 days
4. Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 90 days of randomization
5. Planned cardiac surgery or revascularization.
6. Uncontrolled diabetes mellitius (HbA1c>8.0%）.
7. Uncontrolled hypertension.
8. Other conditions that the researchers considered inappropriate to participate in the study.

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 for 24 weeks; 40 patients will be enrolled in this arm	Biological: Ongericimab; Administered by subcutaneous injection; Other Names: JS002
Placebo Comparator: placebo 150mg Q2W for 24 weeks; 20 patients will be enrolled in this arm	Drug: Placebo; Administered by subcutaneous injection
Experimental: JS002 450mg Q4W for 24 weeks; 40 patients will be enrolled in this arm	Biological: Ongericimab; Administered by subcutaneous injection; Other Names: JS002
Placebo Comparator: placebo 450mg Q4W for 24 weeks; 20 patients will be enrolled in this arm	Drug: Placebo; Administered by subcutaneous injection

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects who develop detectable anti-drug antibodies (ADAs)	ADA was quantified using the Bridging-ECLIA	from baseline to 32 weeks

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2021
• Primary Completion (Actual): May 8, 2023
• Study Completion (Actual): June 29, 2023

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: JS002-005

Drug and device information, study documents

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