Study of Efficacy and Safety of Inclisiran in Asian Participants With Atherosclerotic Cardiovascular Disease (ASCVD) or ASCVD High Risk and Elevated Low Density Lipoprotein Cholesterol (LDL-C)

Phase 3

Active, not recruiting

• Conditions: Hypercholesterolemia
• Interventions: Drug: inclisiran sodium; Drug: Placebo

• Registration Number: NCT04765657
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

A multicenter study to evaluate safety and efficacy of inclisiran in Asian patients with ASCVD or ASCVD high risk and elevated LDL-C

Detailed Description

The purpose of the study is to demonstrate the efficacy and safety of inclisiran sodium 300mg to support the indication for LDL-C reduction of inclisiran in Asian patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-high risk patients with elevated LDL-C as an adjunct to diet and maximally tolerated dose statins with or without additional lipid-lowering therapy.

A core part (2-week screening period and a 12-month double-blinded treatment period), and an extension part (until reasonable access to the IMP post product launch provided for the participants)

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-02-05
• Study First Submitted QC: 2021-02-19
• Study First Posted: 2021-02-21
• Study Start: 2021-03-01
• Primary Completion: 2022-06-09
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-25
• Last Update Posted: 2024-12-27
• Study Completion: 2026-12-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 345

Inclusion Criteria

-At screening participants with: ASCVD (including acute coronary syndrome (ACS), stable coronary heart disease, post revascularization, ischemic cardiomyopathy, ischemic stroke, transient ischemic attack (TIA), and peripheral atherosclerosis) and Serum LDL-C ≥1.8 mmol/L (≥70 mg/dL) OR ASCVD high risk (LDL-C ≥4.9 mmol/L, diabetes, high 10-year ASCVD risk assessed by Chinese ASCVD Risk Assessment Flow Chart , or high risk per local guidelines with a target LDL-C of <100 mg/dL) and Serum LDL-C ≥2.6 mmol/L (≥100 mg/dL)

• Fasting triglyceride < 400 mg/dL (< 4.52 mmol/L) at screening.
• Participants on statins should be receiving a maximally tolerated dose . Maximum tolerated dose is defined as the maximum dose of statin that can be taken on a regular basis without intolerable AE. Intolerance to any dose of statin must be documented as historical AEs attributed to the statin in question on the source documentation and on the Medical history page of the eCRF
• Participants not receiving statin must have a documented evidence of intolerance to all doses of at least 2 different statins(or the corresponding local definition of complete intolerance to statins)
• Participants following lifestyle modification should be on the therapy of LDL-C lowering (such as statin monotherapy, or statin incombination with ezetimibe) with a stable dose for ≥30 days before screening and have no planned medication or dose change during study participation.
• Participants are willing and able to give informed consent before initiation of any study related procedures and willing to comply with all required study procedures.

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Exclusion Criteria

• New York Heart Association (NYHA) class IV heart failure or last known left ventricular ejection fraction <25%.
• Cardiac arrhythmia with clinical significance within 3 months prior to randomization that is not controlled by medication or via ablation.
• Major adverse cardiovascular event within 3 months prior to randomization.
• Uncontrolled severe hypertension: systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg prior to randomization despite antihypertensive therapy.
• Calculated glomerular filtration rate ≤30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology.
• Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 2 years.
• History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the three years prior to randomization.
• Barrier method: Condom or Occlusive cap (e.g. diaphragm or cervical/vault caps).
• Other protocol-defined inclusion/exclusion criteria may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
inclisiran sodium 300 mg	inclisiran sodium	Subcutaneous injection
Placebo	Placebo	Subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Core: Percentage change in low- density lipoprotein cholesterol (LDL-C)	Baseline, Day 330	Superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330
Extension: Number of participants with Adverse Events	Day 360 until study completion, an average of 3 years	Evaluation of the safety and tolerability of inclisiran, treatment emergent Adverse events and Serious Adverse Events

Secondary Outcome Measures

Name	Time	Method
Core: Proportion of participants in each group with ≥ 50% LDL-C reduction	From baseline to Day 330	The superiority of inclisiran compared to placebo in individual response rate for lipid controlling
Core: Proportion of participants in each group who attain global lipid targets for their level of ASCVD risk (55mg/dl for ASCVD patients, 70mg/dl for ASCVD high risk patients)	Day 330	The superiority of inclisiran compared to placebo in individual response rate for lipid controlling
Core: Percentage change in total cholesterol, ApoB, non-HDL-C, ApoA1, HDL-C, Lp(a) and triglycerides	From baseline to Day 330	The superiority of inclisiran compared to placebo in reducing other lipids, lipoproteins and apolipoproteins
Core: Absolute change in total cholesterol, ApoB, non-HDL-C, ApoA1, HDL-C, Lp(a) and triglycerides	From baseline to Day 330	The superiority of inclisiran compared to placebo in reducing other lipids, lipoproteins and apolipoproteins
Core: Time adjusted absolute change in LDL-C	From baseline after Day 90 and up to Day 360	The superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330 and over time
Core: Percentage change in PCSK9	From baseline to Day 330	The superiority of inclisiran compared to placebo in reducing PCSK9 from baseline to Day 330
Core: Absolute change in PCSK9	From baseline to Day 330	The superiority of inclisiran compared to placebo in reducing PCSK9 from baseline to Day 330
Core: Proportion of participants reaching LDL-C levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL	Day 330	The superiority of inclisiran compared to placebo in individual response rate for lipid controlling
Core: Time adjusted percentage change in LDL-C	From baseline after Day 90 and up to Day 360	The superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330 and over time
Core: Absolute change in LDL-C	From baseline to Day 330	The superiority of inclisiran compared to placebo in reducing LDL-C from baseline to Day 330 and over time

Trial Locations

Locations (1)

Novartis Investigative Site; 🇨🇳 Taipei, Taiwan