Efficacy and Safety of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-lowering Therapy.

Novartis Pharmaceuticals350 enrolled

Overview

CKJX839D12304 was a research study to determine if the study treatment, called inclisiran, in comparison to placebo and ezetimibe effectively reduces Low-Density Lipoprotein Cholesterol (LDL-C) as measured by percentage change from baseline to Day 150. This study was conducted in eligible participants with primary hypercholesterolemia not receiving any lipid-lowering therapy (LLT), with a 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk of less than 7.5%.

This study was a randomized, double-blind, placebo- and active comparator-controlled, multicenter study in 350 adult participants with primary hypercholesterolemia not receiving any LLT with a 10-year ASCVD risk score of less than 7.5%. This study evaluated the efficacy and safety of inclisiran sodium 300 mg, administered as a monotherapy in comparison to ezetimibe and placebo. The study consisted of: * a screening period of up to 14 days; * a double-blind treatment period of 150+/- 5 days during which participants were randomly assigned to either the inclisiran arm, the ezetimibe arm or the placebo arm in a 2:1:1 ratio; and * a safety follow-up / End of Study visit conducted 30+5 days after the Day 150 visit. The overall study duration was approximately 190 days.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

350

Conditions

Hypercholesterolemia

Interventions

InclisiranDRUG

284 mg (equivalent to 300 mg inclisiran sodium) subcutaneous injection given on Day 1 and Day 90

EzetimibeDRUG

10 mg over-encapsulated tablet taken once a day from Day 1 through Day 149

Matching Placebo for InclisiranDRUG

0mg placebo injection solution for subcutaneous injection on Day 1 and Day 90

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria at screening: * informed consent signed prior to participation in study * fasting LDL-C of \>= 100 mg/dL but \< 190 mg/dL * fasting triglycerides \<= 400 mg/dL * 10-year ASCVD risk score \< 7.5% * not on any lipid-lowering therapy within 90 days of screening Key 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 (TSH above upper limit of normal)

Locations (42)

Outcomes

Primary Outcomes

Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150

Percentage change in LDL-C from Baseline (day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo. There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows: * Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen. * Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Time frame: Baseline, Day 150

Secondary Outcomes

Absolute Change in LDL-C From Baseline to Day 150

Absolute change in LDL-C from Baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo. There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows: * Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen. * Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Time frame: Baseline, Day 150

Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 150

Data from ClinicalTrials.gov

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Percentage Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Day 150

Percentage change in non-HDL-C from Baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo. There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows: * Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen. * Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Time frame: Baseline, Day 150

Percentage Change in Total Cholesterol (TC)/HDL-C Ratio From Baseline to Day 150

Percentage change in total cholesterol/HDL-C ratio from Baseline (Day1) to Day 150, Inclisiran arm versus Ezetimibe and placebo. There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows: * Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen. * Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strate

Time frame: Baseline, Day 150

Percentage Change in Apolipoprotein B (Apo B) From Baseline to Day 150

Percentage change in Apo B from Baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo. There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows: * Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen. * Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Time frame: Baseline, Day 150

Percentage Change in Apo B/Apo A-1 Ratio From Baseline to Day 150

Percentage change in Apo B/Apo A-1 ratio from baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo. There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows: * Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen. * Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Time frame: Baseline, Day 150