Efficacy and Safety of SHR-1209 Combined With Lipid-lowering Agents in Patients With Hypercholesterolemia

A Multicentre, Randomized, Double-blind, Placebo-controlled, Phase III Study to Evaluate the Efficacy and Safety of SHR-1209 Combined With Lipid-lowering Agents in the Stable Treatment of Patients With Non-familial Hypercholesterolemia and Mixed Hyperlipidemia .

To evaluate the efficacy, safety, pharmacokinetics and immunogenicity of SHR-1209 subcutaneous administration in patients with non-familial hypercholesterolemia and mixed hyperlipidemia after lipid-lowering therapy

Study Overview

• Status: Completed
• Conditions: Mixed Hyperlipidemia; Non-familial Hypercholesterolemia
• Intervention / Treatment: Drug: SHR-1209 ;placebo; Drug: SHR-1209 ;placebo; Drug: SHR-1209 ;placebo

• Study Type: Interventional
• Enrollment (Actual): 692
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100029
      • Beijing Anzhen Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 and ≤80 on the date of signing the informed consent, male or female;
2. The report of LDL-C should be higher than the ideal lipid-lowering target according to ASCVD history;
3. Fasting triglycerides less than equal to 5.6 mmol/L；
4. Understand the study procedures and methods, volunteer to participate in the study, and sign the informed consent.

Exclusion Criteria:

1. Have the following diseases or treatment history : (1) Have known allergic reaction to experimental drugs, or have severe allergic reaction to other antibody drugs;(2) previous diagnosis of familial hypercholesterolemia according to Simon Broome Criteria;(3) cardiac function as defined by the New York Heart Association (NYHA) grade III-IV at screening or randomization or latest detected LVEF<30%;(4) CVD events within 3 months; (5) uncontrolled hypertension; (6) prior exposure to recaticimab or other PCSK9 inhibitors; (7) inadequate organ functions.
2. Any of the laboratory indicators met the following criteria at screening or at randomization :(1) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 3 times the upper limit of normal (ULN), or total bilirubin exceeding 2 times the upper limit of normal (ULN);(2) Creatine kinase (CK) exceeds 3 times the upper limit of normal value (ULN);
3. General conditions :(1) the investigator judged that subcutaneous injection was not appropriate;(2) Fertile female subjects who did not use contraception within 4 weeks before screening; Or male or female subjects who do not agree to use high-efficiency contraceptives during the trial and for 24 weeks after the last dosing;(3) Women who are pregnant or lactating.
4. The Investigator determines that the subjects have poor compliance or have any factors that may prevent them from participating in the study, including, but not limited to, the study placing the subjects at unacceptable risk or possibly interfering with the study results.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1：SHR-1209 / placebo	Drug: SHR-1209 ;placebo; SHR-1209 and placebo 150 mg subcutaneous injection once every 4 weeks for 48 weeks; Drug: SHR-1209 ;placebo; SHR-1209 and placebo 300 mg subcutaneous injection once every 8 weeks for 48 weeks; Drug: SHR-1209 ;placebo; SHR-1209 and placebo 450 mg subcutaneous injection once every 12 weeks for 48 weeks
Experimental: Cohort 2：SHR-1209 /placebo	Drug: SHR-1209 ;placebo; SHR-1209 and placebo 150 mg subcutaneous injection once every 4 weeks for 48 weeks; Drug: SHR-1209 ;placebo; SHR-1209 and placebo 300 mg subcutaneous injection once every 8 weeks for 48 weeks; Drug: SHR-1209 ;placebo; SHR-1209 and placebo 450 mg subcutaneous injection once every 12 weeks for 48 weeks
Experimental: Cohort 3：SHR-1209 / placebo	Drug: SHR-1209 ;placebo; SHR-1209 and placebo 150 mg subcutaneous injection once every 4 weeks for 48 weeks; Drug: SHR-1209 ;placebo; SHR-1209 and placebo 300 mg subcutaneous injection once every 8 weeks for 48 weeks; Drug: SHR-1209 ;placebo; SHR-1209 and placebo 450 mg subcutaneous injection once every 12 weeks for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage change in LDL-C relative to baseline	at 24 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
The value of change in LDL-C relative to baseline	at 24 weeks of treatment
Percentage change in LDL-C relative to baseline	at 48 weeks of treatment;
The value of change in LDL-C relative to baseline ,	at 48 weeks of treatment;
Percentage change in non-HDL-C relative to baseline	at 24 weeks of treatment;
Percentage change in non-HDL-C relative to baseline	at 48 weeks of treatment;
Percentage change in ApoB relative to baseline	at 24 weeks of treatment;
Percentage change in ApoB relative to baseline	at 48 weeks of treatment;
Percentage change in TC/HDL-C relative to baseline	at 24 weeks of treatment;
Percentage change in TC/HDL-C relative to baseline,	at 48 weeks of treatment
Percentage change in ApoB/ApoA1 relative to baseline,	at 24 weeks of treatment;
Percentage change in ApoB/ApoA1 relative to baseline,	at 48 weeks of treatment;
Percentage change in LP (a) relative to baseline,	at 24 weeks of treatment;
Percentage change in LP (a) relative to baseline,	at 48 weeks of treatment;
Percentage change in TG relative to baseline	at 24 weeks of treatment
Percentage change in TG relative to baseline	at 48 weeks of treatment;
Percentage of patients who achieved LDL-C goal according to presence of ASCVD at baseline,	at 48 weeks of treatment;
Percentage of patients who achieved LDL-C goal according to presence of ASCVD at baseline,	at 48 weeks of treatment.

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2021
• Primary Completion (Actual): May 23, 2023
• Study Completion (Actual): May 23, 2023

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: May 7, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hypertriglyceridemia; Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemias; Hyperlipidemia, Familial Combined; Lipidoses; Hyperlipoproteinemia Type V
• Other Study ID Numbers: SHR-1209-302

Drug and device information, study documents

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