The purpose of this study was 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 were not on any lipid lowering therapy.
This study was designed as a randomized, double-blind, multi-center Phase III trial, with a placebo-controlled treatment period and an open label treatment period, to evaluate the efficacy and safety of inclisiran sodium 300 mg s.c. in participants aged 18 to 75 years with a low or moderate ASCVD risk and fasting LDL-C value of ≥ 130 mg/dL but \< 190 mg/dL who were not on any lipid lowering therapy. The study consisted of 3 parts: * Screening: the screening period was up to 14 days to allow adequate time for the eligibility evaluations. * Core Part: a double-blind, placebo-controlled treatment period of 180 days in which eligible participants were randomized 1:1 to receive either inclisiran sodium 300 mg s.c. (inclisiran group) or matching placebo s.c. (control group) on Day 1 and Day 90. The end of core part (EOC) visit was conducted on Day 180. The database lock for the core part was planned to occur after all randomized participants have completed the EOC visit (or have discontinued from the study before EOC). The primary analysis was conducted after the database lock for the core part. • Extension Part: an extended treatment period of 180 days. In the extension part, participants originally randomized to inclisiran in the core part were to continue the inclisiran treatment while participants initially randomized to placebo were to transit to the inclisiran. The extension part was to start from the Day 180 treatment dose (placebo in the inclisiran group and inclisiran for participants originally randomized to the control group).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
207
Inclisiran s.c
Matching s.c. placebo
Novartis Investigative Site
Fuzhou, Fujian, China
Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Low-density lipoprotein cholesterol is a type of lipoprotein in the blood. Lipoproteins are particles made of lipids(fats) and proteins that carry fats through the bloodstream. Because of their structure, fats can't move through the blood on their own. So, lipoproteins carry fats to various cells in the body.
Time frame: Baseline, Day 150
Absolute Change in LDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Low-density lipoprotein cholesterol is a type of lipoprotein in the blood. Lipoproteins are particles made of lipids(fats) and proteins that carry fats through the bloodstream. Because of their structure, fats can't move through the blood on their own. So, lipoproteins carry fats to various cells in the body.
Time frame: Baseline, Day 150
Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) (ng/mL) From Baseline at Day 150 - Core Analysis: Core Part
Inclisiran is a double-stranded small interfering ribonucleic acid (siRNA) that causes degradation of protein convertase subtilisin/kexin type 9 (PCSK9) messenger RNA (mRNA) leading to the reduction of PCSK9 protein. The percentage change from baseline in PCSK9 at Day 150 was assessed.
Time frame: Baseline, Day 150
Absolute Change in PCSK9 (ng/mL) From Baseline at Day 150 - Core Analysis: Core Part
Inclisiran is a double-stranded small interfering ribonucleic acid (siRNA) that causes degradation of protein convertase subtilisin/kexin type 9 (PCSK9) messenger RNA (mRNA) leading to the reduction of PCSK9 protein.
Time frame: Baseline, Day 150
Percentage Change in Total Cholesterol (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
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Novartis Investigative Site
Guangzhou, Guangdong, China
Novartis Investigative Site
Guangzhou, Guangdong, China
Novartis Investigative Site
Zhongshan, Guangdong, China
Novartis Investigative Site
Wuhan, Hubei, China
Novartis Investigative Site
Changsha, Hunan, China
Novartis Investigative Site
Changsha, Hunan, China
Novartis Investigative Site
Hohhot, Inner Mongolia, China
Novartis Investigative Site
Changzhou, Jiangsu, China
Novartis Investigative Site
Xuzhou, Jiangsu, China
...and 18 more locations
Total cholesterol is a measure of all the cholesterol in the blood. It includes low-density lipoprotein (LDL), high-density lipoprotein (HDL) and a portion of triglycerides.
Time frame: Baseline, Day 150
Absolute Change in Total Cholesterol (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Total cholesterol is a measure of all the cholesterol in the blood. It includes low-density lipoprotein (LDL), high-density lipoprotein (HDL) and a portion of triglycerides.
Time frame: Baseline, Day 150
Percentage Change in High-density Lipoprotein Cholesterol (HDL-C) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
HDL-C stands for high-density lipoprotein cholesterol, often referred to as the "good" cholesterol. This is because HDL cholesterol helps remove other forms of cholesterol from the bloodstream. It picks up excess cholesterol in the blood and carries it back to the liver, where it is broken down and flushed out of the body.
Time frame: Baseline, Day 150
Absolute Change in HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
HDL-C stands for high-density lipoprotein cholesterol, often referred to as the "good" cholesterol. This is because HDL cholesterol helps remove other forms of cholesterol from the bloodstream. It picks up excess cholesterol in the blood and carries it back to the liver, where it is broken down and flushed out of the body.
Time frame: Baseline, Day 150
Percentage Change in Non-HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Non-HDL cholesterol is a measure of all the "bad" types of cholesterol in the blood, excluding HDL cholesterol. It is calculated by subtracting HDL cholesterol from total cholesterol. Non-HDL cholesterol includes all the types of cholesterol other than HDL cholesterol, and higher levels of non-HDL cholesterol can increase the risk of cardiovascular disease.
Time frame: Baseline, Day 150
Absolute Change in Non-HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Non-HDL cholesterol is a measure of all the "bad" types of cholesterol in the blood, excluding HDL cholesterol. It is calculated by subtracting HDL cholesterol from total cholesterol. Non-HDL cholesterol includes all the types of cholesterol other than HDL cholesterol, and higher levels of non-HDL cholesterol can increase the risk of cardiovascular disease.
Time frame: Baseline, Day 150
Percentage Change in Apolipoprotein B (ApoB) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Apolipoprotein B (ApoB) is a protein that helps carry fat and cholesterol through the body. It is encoded by the APOB gene. ApoB attaches to negative types of cholesterol that cause plaque buildup in blood vessels, which can lead to damage and heart disease.
Time frame: Baseline, Day 150
Absolute Change in ApoB (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Apolipoprotein B (ApoB) is a protein that helps carry fat and cholesterol through the body. It is encoded by the APOB gene. ApoB attaches to negative types of cholesterol that cause plaque buildup in blood vessels, which can lead to damage and heart disease.
Time frame: Baseline, Day 150
Percentage Change in Apolipoprotein A-1 (ApoA-1) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Apolipoprotein A1 (ApoA1) is the primary protein associated with high-density lipoprotein (HDL) particles, and plays a central role in reverse cholesterol transport. HDL cholesterol (HDL-C) and ApoA1 concentrations are inversely related to the risk for coronary artery disease (CAD).
Time frame: Baseline, Day 150
Absolute Change in ApoA-1 (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Apolipoprotein A1 (ApoA1) is the primary protein associated with high-density lipoprotein (HDL) particles, and plays a central role in reverse cholesterol transport. HDL cholesterol (HDL-C) and ApoA1 concentrations are inversely related to the risk for coronary artery disease (CAD).
Time frame: Baseline, Day 150
Percentage Change in Lipoprotein (a) (Lp(a)) (Nmol/L) From Baseline at Day 150 - Core Analysis: Core Part
Often referred to as Lp(a), lipoprotein (a) is a type of lipoprotein that is genetically inherited and in high levels is a common independent risk factor for heart disease.
Time frame: Baseline, Day 150
Absolute Change in Log-transformed Lp(a) (Nmol/L) From Baseline at Day 150 - Core Analysis: Core Part
Often referred to as Lp(a), lipoprotein (a) is a type of lipoprotein that is genetically inherited and in high levels is a common independent risk factor for heart disease.
Time frame: Baseline, Day 150
Percentage Change in Triglyceride (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Triglycerides are fats from the food we eat. Most of the fats we eat (like butter) are in triglyceride form. Extra calories, alcohol and sugar in the body turn into triglycerides. The body stores them in fat cells throughout the body.
Time frame: Baseline, Day 150
Absolute Change in Triglyceride (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
Triglycerides are fats from the food we eat. Most of the fats we eat (like butter) are in triglyceride form. Extra calories, alcohol and sugar in the body turn into triglycerides. The body stores them in fat cells throughout the body.
Time frame: Baseline, Day 150
Percentage Change in LDL-C (mg/dL) From Baseline at Day 330 - Final Analysis: Core Part + Extension Part
Low-density lipoprotein cholesterol is a type of lipoprotein in the blood. Lipoproteins are particles made of lipids(fats) and proteins that carry fats through the bloodstream. Because of their structure, fats can't move through the blood on their own. So, lipoproteins carry fats to various cells in the body.
Time frame: Baseline, Day 330
Absolute Change in LDL-C (mg/dL) From Baseline at Day 330 - Final Analysis: Core Part + Extension Part
Low-density lipoprotein cholesterol is a type of lipoprotein in the blood. Lipoproteins are particles made of lipids(fats) and proteins that carry fats through the bloodstream. Because of their structure, fats can't move through the blood on their own. So, lipoproteins carry fats to various cells in the body.
Time frame: Baseline, Day 330
Number of Participants With Adverse Events (AEs) During Core Part
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject
Time frame: Core part, from treatment start (Day 1) to Day 150
Number of Participants With Adverse Events (AEs) During Extension Part
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject
Time frame: Extension part, from Day 181, up to Day 360
Number of Participants With Adverse Events (AEs) - Cumulative Data (Core + Extension Part)
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject
Time frame: AEs are reported from first dose of study treatment until end of study treatment plus 30 days after the last study visit (or 90 days after the last administration of study drug, whichever is longer) up to a maximum timeframe of approximately 360 days