Study of Inclisiran to prevent Cardiovascular (CV) events in participants with established Cardiovascular disease

Phase 3

Conditions: Health Condition 1: I709- Other and unspecified atherosclerosis

Registration Number: CTRI/2021/12/038730

Lead Sponsor: ovartis Healthcare Pvt Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

Male or female aged =40 years of age

Fasting LDL-C =1.8 mmol/L (70 mg/dL) at the Screening Visit

At the Screening Visit, participants must be on a stable (4 weeks) and well-tolerated lipid-lowering regimen (including e.g. with or without Ezetimibe) that must include a high-intensity statin therapy with either atorvastatin 40 mg QD or rosuvastatin 20 mg QD

Established CV disease defined as any of the following:

Previous myocardial infarction

Previous ischemic stroke

Previous symptomatic PAD, as evidenced by either intermittent claudication with ABI <0.85, prior peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease

Exclusion Criteria

ACS, ischemic stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease <4 weeks prior to the first study visit

Treatment with PCSK9 monoclonal antibodies (e.g., evolocumab, alirocumab) within 90 days

Previous exposure to inclisiran or any other non-mAb PCSK9 targeted therapy, either as an investigational or marketed drug within the prior 2 years

Active liver disease (Participants who enter the Statin Optimization Period must have AST and ALT =3x ULN (as defined by local laboratory reference ranges) at the Statin Optimization Screening Visit to be allowed to continue in the Statin Optimization Period)

NYHA class III & IV heart failure

Severe, concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 5 years

Women of child-bearing potential, unless they are using effective methods of contraception during the course of the trial

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary objective of this study is to demonstrate the superiority of inclisiran compared to placebo in reducing the risk of 3P-MACE (cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke) in participants with established ASCVD and LDL-C =1.8 mmol/L (70 mg/dL) <br/ ><br>Timepoint: Assessment time point- starting from 3 months post baseline till end of study at a 6 monthly interval.

Secondary Outcome Measures

Name	Time	Method
To demonstrate the superiority of inclisiran compared to placebo in reducing the risk of cardiovascular death <br/ ><br>To demonstrate the superiority of inclisiran compared to placebo in reducing the risk of 4P-MACE (composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent revascularization) <br/ ><br>To evaluate inclisiran compared to placebo in reducing the risk of all-cause death <br/ ><br>Timepoint: End point- Time to Death or Time to first occurrence of any of the component of 4P-MACE