Efficacy and Safety of Inclisiran as Monotherapy in Chinese Adults With Low or Moderate ASCVD Risk and Elevated Low-density Lipoprotein Cholesterol.
- Conditions
- Primary Hypercholesterolemia or Mixed Dyslipidemia
- Interventions
- Drug: Matching Placebo for Inclisiran
- Registration Number
- NCT05888103
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 207
- 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
- Use of any LLT within 90 days prior to screening visit
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Inclisiran - Inclisiran Inclisiran Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) s.c administered on Day 1, Day 90, and Day 270, and placebo on Day 180 Inclisiran - Inclisiran Matching Placebo for Inclisiran Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) s.c administered on Day 1, Day 90, and Day 270, and placebo on Day 180 Placebo- Inclisiran Inclisiran Placebo on Day 1 and Day 90 and Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) s.c on Day 180 and 270 Placebo- Inclisiran Matching Placebo for Inclisiran Placebo on Day 1 and Day 90 and Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) s.c on Day 180 and 270
- Primary Outcome Measures
Name Time Method Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
- Secondary Outcome Measures
Name Time Method Absolute Change in Log-transformed Lp(a) (Nmol/L) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Percentage Change in Triglyceride (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Absolute Change in Triglyceride (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Number of Participants With Adverse Events (AEs) During Core Part Core part, from treatment start (Day 1) to Day 150 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
Number of Participants With Adverse Events (AEs) During Extension Part Extension part, from Day 181, up to Day 360 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
Percentage Change in LDL-C (mg/dL) From Baseline at Day 330 - Final Analysis: Core Part + Extension Part Baseline, Day 330 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.
Absolute Change in LDL-C (mg/dL) From Baseline at Day 330 - Final Analysis: Core Part + Extension Part Baseline, Day 330 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.
Number of Participants With Adverse Events (AEs) - Cumulative Data (Core + Extension Part) 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 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
Absolute Change in LDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) (ng/mL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Absolute Change in PCSK9 (ng/mL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Absolute Change in HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Percentage Change in Total Cholesterol (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Absolute Change in Total Cholesterol (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Percentage Change in Non-HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Absolute Change in Non-HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Percentage Change in Apolipoprotein B (ApoB) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Absolute Change in ApoB (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Percentage Change in Apolipoprotein A-1 (ApoA-1) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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).
Absolute Change in ApoA-1 (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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).
Percentage Change in Lipoprotein (a) (Lp(a)) (Nmol/L) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Percentage Change in High-density Lipoprotein Cholesterol (HDL-C) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part Baseline, Day 150 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.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇨🇳Tianjin, China