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Completed

NCT Number: NCT05763875

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

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%.

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Key information

Conditions

Hypercholesterolemia Dyslipidemias Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, Barranquilla, Atlántico, Colombia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Inclisiran

Drug

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

Other names: KJX839

ezetimibe

Drug

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

Other names: Sandoz ezetimibe

Matching Placebo for Inclisiran

Drug

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

Other names: Placebo s.c.

Matching Placebo for Ezetimibe

Drug

0mg over-encapsulated placebo tablet taken once a day from Day 1 through Day 149

Other names: Placebo p.o.

Primary outcomes

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

    Time frame: Baseline, 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.

Secondary outcomes

  1. Absolute Change in LDL-C From Baseline to Day 150

    Time frame: Baseline, 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.

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

    Time frame: Baseline, Day 150

    Percentage change in PCSK9 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.

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

    Time frame: Baseline, 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.

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

    Time frame: Baseline, 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

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

    Time frame: Baseline, 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.

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

    Time frame: Baseline, 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.

  7. Change in Lipoprotein (a) [Lp(a)] From Baseline to Day 150

    Time frame: Baseline, Day 150

    Day 150 / Baseline ratio in Lp(a) in 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.

  8. Incidence of Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)

    Time frame: From first dose of study treatment on Day 1 up to Day 180

    Incidence of TEAEs (regardless of seriousness) and SAEs by treatment group, including changes in laboratory results qualifying and reported as AEs.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Double-blind, Randomized, Placebo- and Active-Comparator Controlled Study to Evaluate the Efficacy of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-Lowering Therapy (VictORION-Mono)

Acronym: V-Mono

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Mar 10, 2023
Registry last updated
Oct 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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