A Study Of SHR-1918 In Participants With Hypercholesterolemia With Inadequate Lipid Control on Statins Plus PCSK9 Inhibitors

Official title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II/III Study to Evaluate the Efficacy and Safety of SHR-1918 in Patients With Hypercholesterolemia With Inadequate Lipid Control on Statins Plus PCSK9 Inhibitors

Overview

The purpose of the study is to evaluate the efficacy and safety of SHR-1918 in patients with hypercholesterolemia with inadequate lipid control on statins plus PCSK9 inhibitors. The efficacy and safety of SHR-1918 will be evaluated after 12-weeks and 24-weeks treatment.

Interventions

• Drug SHR-1918 Injection
  SHR-1918 injection.
• Drug SHR-1918 Injection Placebo
  SHR-1918 injection placebo.

Primary outcome measures

• Percentage change in low density lipoprotein cholesterol (LDL-C) levels at Week 12 relative to baseline. [Time frame: At 12 weeks of treatment.]
• Percentage change in low density lipoprotein cholesterol (LDL-C) levels at Week 24 relative to baseline. [Time frame: At 24 weeks of treatment.]

Secondary outcome measures (12)

• Percentage change in non-high-density lipoprotein cholesterol (non-HDL-C) relative to baseline. [Time frame: At 12 weeks of treatment.]
• Percentage change in triglyceride (TG) relative to baseline. [Time frame: At 12 weeks of treatment.]
• Percentage change in total cholesterol (TC) relative to baseline. [Time frame: At 12 weeks of treatment.]
• Percentage change in apolipoprotein B (ApoB) relative to baseline. [Time frame: At 12 weeks of treatment.]
• Percentage change in Apolipoprotein A1 (ApoA1) relative to baseline. [Time frame: At 12 weeks of treatment.]
• Change in triglyceride (TG) relative to baseline. [Time frame: At 12 weeks of treatment.]
• Change in non-high-density lipoprotein cholesterol (non-HDL-C) relative to baseline. [Time frame: At 12 weeks of treatment.]
• Change in total cholesterol (TC) relative to baseline. [Time frame: At 12 weeks of treatment.]
• Change in apolipoprotein B (ApoB) relative to baseline. [Time frame: At 12 weeks of treatment.]
• Change in Apolipoprotein A1 (ApoA1) relative to baseline. [Time frame: AT 12 weeks of treatment.]
• Change in Lipoprotein(a) (Lp(a)) relative to baseline. [Time frame: At 12 weeks of treatment.]
• Percentage change in Lipoprotein(a) (Lp(a)) relative to baseline. [Time frame: At 12 weeks of treatment.]

Eligibility criteria

Inclusion criteria

• Male and female ≥ 18 years old and ≤ 85 years old, who is able and willing to provide a written informed consent.
• TG ≤ 5.6 mmol/L.
• LDL-C ≥ 2.6 mmol/L for moderate to high ASCVD risk, LDL-C ≥ 1.8 mmol/L for very high ASCVD risk, LDL-C ≥ 1.4 mmol/L for ultra-high ASCVD risk.
• Male and female subjects of childbearing potential and their partners must have no plans to donate sperm or become pregnant during the entire study period and after the last dose, and agree to use contraceptive methods as specified in the protocol.

Exclusion criteria

• History of severe allergies/hypersensitivity reactions, or clinically significant allergies/hypersensitivity reactions as judged by the investigator, or history of allergies to drugs with similar chemical structures.
• Heart failure with New York Heart Association (NYHA) Class III-IV prior to screening or randomization.
• Acute ischemic ASCVD events within 3 months prior to screening or randomization.
• Have severe cardiac arrhythmia within 3 months prior to screening or randomization.
• Echocardiography indicates a left ventricular ejection fraction (LVEF) of less than 30% within 3 months prior to screening.
• History of percutaneous coronary intervention, history of coronary artery bypass grafting (CABG), history of peripheral arterial revascularisation within 1 month prior to screening or randomization.
• Poorly controlled type 2 diabetes mellitus or previously diagnosed type 1 diabetes mellitus; poorly controlled hypertension.
• Have a history of diseases that significantly affect blood lipid levels, such as nephrotic syndrome, severe liver diseases, Cushing's syndrome, or have severe arrhythmia prior to screening or randomization.
• Malignant tumors within 5 years.
• It's planned to research transcutaneous coronary intervention, coronary artery bypass grafting, carotid or peripheral artery reconstruction, pacemaker implantation, cardiac resynchronisation therapy (CRT), implantable cardioverter defibrillator (ICD) implantation and other implantations during the study.
• Received plasma exchange therapy within 2 months prior to screening, or plans to receive plasma exchange therapy during the study period, or has received LDL receptor gene therapy prior to screening.
• Have a history of major surgery within 3 months prior to screening, or plans to undergo major surgery during the study period.
• History of drug use, substance abuse, and alcohol abuse.
• Participated in or is participating in other clinical studies and has received study interventions within the past month prior to screening.
• Researchers determine that the subject has poor compliance or any factors that make them unsuitable for participation in this trial, including but not limited to participation in the study placing the subject at unacceptable risk or potentially interfering with the study results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Nanjing First Hospital — Nanjing

Identifiers

NCT: NCT07404553 · SHR-1918-303

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗