Efficacy and Safety of Inclisiran as Monotherapy in Chinese Adults With Low or Moderate ASCVD Risk and Elevated Low-density Lipoprotein Cholesterol.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of inclisiran as a monotherapy in Chinese adults with low or moderate atherosclerotic cardiovascular disease (ASCVD) risk and elevated low-density lipoprotein cholesterol (LDL-C) who are not on any lipid lowering therapy.

Detailed Description
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This study is designed as a randomized, double-blind, multi-center phase 3 trial, with a placebo-controlled period and an open label treatment period, to evaluate the efficacy and safety of inclisiran sodium 300mg s.c. in participants aged 18 75 years with low or moderate ASCVD risk and fasting LDL-C value of ≥ 130 mg/dL but < 190 mg/dL who are not on any lipid lowering therapy.

Official Title
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A 6 Month Randomized, Double-blind, Placebo-controlled Study Followed by a 6 Month Open- Label Extension to Assess the Efficacy and Safety of Inclisiran as Monotherapy in Chinese Adults With Low or Moderate ASCVD Risk and Elevated Low-density Lipoprotein Cholesterol

Conditions
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Primary Hypercholesterolemia or Mixed Dyslipidemia

Intervention / Treatment
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* Drug: Inclisiran
* Drug: Matching Placebo for Inclisiran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Fasting LDL-C of ≥ 130 mg/dL but < 190 mg/dL Triglycerides ≤ 400 mg/dL Categorized as low or moderate ASCVD risk by the 2016 Chinese Guideline Exclusion Criteria: History of ASCVD Diabetes mellitus or fasting plasma glucose of ≥ 7.0 mmol/L or HbA1c ≥ 6.5% Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-center, randomized, double-blind, placebo-controlled, parallel groups
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inclisiran<br>Inclisiran s.c | Drug: Inclisiran<br>* Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran*) in 1.5 mL<br>* Other names: KJX839;|
| Placebo Comparator: Placebo<br>Placebo s.c. | Drug: Matching Placebo for Inclisiran<br>* Matching s.c. placebo in 1.5 mL<br>* Other names: Placebo s.c.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in Low-density Lipoprotein Cholesterol(LDL-C) from baseline | Percentage change in Low-density Lipoprotein Cholesterol (LDL-C) from Baseline at Day 150 compared to placebo | Baseline, Day 150 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in low-density lipoprotein cholesterol (LDL-C) from baseline | Absolute change in LDL-C from baseline at Day 150 compared to placebo | Baseline, Day 150 | 
| Percentage change from baseline in protein convertase subtilisin/kexin type 9 (PCSK9) | Percentage change from baseline at Day 150 in PCSK9 compared to placebo | Baseline, Day 150 | 
| Absolute change from baseline in protein convertase subtilisin/kexin type 9 (PCSK9) | Absolute change from baseline at Day 150 in PCSK9 compared to placebo | Baseline, Day 150 | 
| Percentage change from baseline in total cholesterol | Percentage change from baseline at Day 150 in total cholesterol (TC) compared to placebo | Baseline, Day 150 | 
| Percentage change from baseline in high-density lipoprotein cholesterol (HDL-C) | Percentage change from baseline at Day 150 in HDL-C compared to placebo | Baseline, Day 150 | 
| Percentage change from baseline in non-HDL-C | Percentage change from baseline at Day 150 in non-HDL-C compared to placebo | Baseline, Day 150 | 
| Percentage change from baseline in apolipoprotein B (ApoB) | Percentage change from baseline at Day 150 in ApoB compared to placebo | Baseline, Day 150 | 
| Percentage change from baseline in apolipoprotein A-1 (ApoA-1) | Percentage change from baseline at Day 150 in ApoA-1 compared to placebo | Baseline, Day 150 | 
| Percentage change from baseline in lipoprotein (a) (Lp(a)) | Percentage change from baseline at Day 150 in Lp(a) compared to placebo | Baseline, day 150 | 
| Percentage change from baseline in triglycerides | Percentage change from baseline at Day 150 in triglycerides (TG) compared to placebo | Baseline, Day 150 | 
| Absolute change from baseline in total cholesterol | Absolute change from baseline at Day 150 in total cholesterol (TC) compared to placebo | Baseline, Day 150 | 
| Absolute change from baseline in high-density lipoprotein cholesterol (HDL-C) | Absolute change from baseline at Day 150 in HDL-C compared to placebo | Baseline, Day 150 | 
| Absolute change from baseline in non-HDL-C | Absolute change from baseline at Day 150 in non-HDL-C compared to placebo | Baseline, Day 150 | 
| Absolute change from baseline in apolipoprotein B (ApoB) | Absolute change from baseline at Day 150 in ApoB compared to placebo | Baseline, Day 150 | 
| Absolute change from baseline in apolipoprotein A-1 (ApoA-1) | Absolute change from baseline at Day 150 in ApoA-1 compared to placebo | Baseline, Day 150 | 
| Absolute change from baseline in lipoprotein (a) (Lp(a)) | Absolute change from baseline at Day 150 in Lp(a) compared to placebo | Baseline, Day 150 | 
| Absolute change from baseline in triglycerides | Absolute change from baseline at Day 150 in triglycerides (TG) compared to placebo | Baseline, Day 150 | 
| Percentage change in LDL-C from baseline for inclisiran group | Percentage change in lipoprotein cholesterol (LDL-C) from baseline at Day 330 for inclisiran group | Baseline, Day 330 | 
| Absolute change in LDL-C from baseline for inclisiran group | Absolute change in lipoprotein cholesterol (LDL-C) from baseline at Day 330 for inclisiran group | Baseline, Day 330 | 
| Number of participants with Adverse Events (AEs) during core part | Adverse Events (AEs), abnormal vital signs and safety laboratory values during core part | Up to 180 days | 
| Number of participants with Adverse Events (AEs) during extension part | Adverse Events (AEs), and abnormal vital signs and safety laboratory values during extension part | From day 181, up to day 360 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inclisiran, LDL-C, monotherapy