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

October 8, 2025 updated by: Novartis Pharmaceuticals

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)

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%.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

350

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Colombia
      • Manizales, Colombia, 170008
        • Novartis Investigative Site
      • San Gil, Colombia, 684031
        • Novartis Investigative Site
    • Atlántico
      • Barranquilla, Atlántico, Colombia, 080012
        • Novartis Investigative Site
    • Santander Department
      • Floridablanca, Santander Department, Colombia, 57-7
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 10787
        • Novartis Investigative Site
      • Bochum, Germany, 44789
        • Novartis Investigative Site
      • Gladbeck, Germany, 45968
        • Novartis Investigative Site
      • Hamburg, Germany, 22607
        • Novartis Investigative Site
      • Papenburg, Germany, 26871
        • Novartis Investigative Site
    • Bavaria
      • Munich, Bavaria, Germany, 80809
        • Novartis Investigative Site
    • Lower Saxony
      • Hanover, Lower Saxony, Germany, 30449
        • Novartis Investigative Site
    • North Rhine-Westphalia
      • Löhne, North Rhine-Westphalia, Germany, 32584
        • Novartis Investigative Site
    • Saxony-Anhalt
      • Jerichow, Saxony-Anhalt, Germany, 39319
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, 1083
        • Novartis Investigative Site
      • Pécs, Hungary, 7623
        • Novartis Investigative Site
  • Mexico
      • Culiacan Sinaloa, Mexico, 80230
        • Novartis Investigative Site
      • Querétaro, Mexico, 76000
        • Novartis Investigative Site
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 64060
        • Novartis Investigative Site
      • Monterrey, Nuevo León, Mexico, 64440
        • Novartis Investigative Site
    • Yucatán
      • Mérida, Yucatán, Mexico, 97070
        • Novartis Investigative Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35215
        • Parkway Medical Center
      • Dothan, Alabama, United States, 36305
        • SEC Clinical Research
    • Florida
      • DeLand, Florida, United States, 32720
        • Hillcrest Medical Research
      • Maitland, Florida, United States, 32751
        • ClinCloud
      • Miami, Florida, United States, 33165
        • Alma Clinical Research Inc
      • Miami Lakes, Florida, United States, 33014
        • Inpatient Research Clinical LLC
      • North Miami Beach, Florida, United States, 33162
        • Harmony Clinical Research
      • Plant City, Florida, United States, 33563
        • Fam Medical Specialists Of Fl Plc
      • Zephyrhills, Florida, United States, 33541
        • Cozy Research LLC
    • Illinois
      • Morton, Illinois, United States, 61550
        • Koch Family Medicine
    • Louisiana
      • Bossier City, Louisiana, United States, 71111
        • Grace Research Llc
      • Shreveport, Louisiana, United States, 71101
        • Grace Research Llc
      • Zachary, Louisiana, United States, 70791
        • Southern Clin Research Clinic
    • New York
      • The Bronx, New York, United States, 10456
        • Prime Global Research Inc
    • North Carolina
      • Monroe, North Carolina, United States, 28112
        • Monroe Biomedical Research
    • North Dakota
      • Fargo, North Dakota, United States, 58103
        • Lillestol Research LLC
    • Ohio
      • Huber Heights, Ohio, United States, 45424
        • Wellnow Urgent Care and Research
    • Oklahoma
      • Edmond, Oklahoma, United States, 73013
        • Conrad Clinical Research
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Compass Point Research
    • Texas
      • Sugar Land, Texas, United States, 77479
        • Mt Olympus Medical Research
    • Virginia
      • Richmond, Virginia, United States, 23219
        • Dominion Medical Associates
    • Wisconsin
      • West Bend, Wisconsin, United States, 53095
        • Spaulding Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Inclisiran
Inclisiran s.c and Placebo p.o
Drug: Inclisiran
284 mg (equivalent to 300 mg inclisiran sodium) subcutaneous injection given on Day 1 and Day 90
Other Names:
  • KJX839
Drug: Matching Placebo for Ezetimibe
0mg over-encapsulated placebo tablet taken once a day from Day 1 through Day 149
Other Names:
  • Placebo p.o.
Active Comparator: Ezetimibe
Placebo s.c. and Ezetimibe p.o.
Drug: Ezetimibe
10 mg over-encapsulated tablet taken once a day from Day 1 through Day 149
Other Names:
  • Sandoz ezetimibe
Drug: Matching Placebo for Inclisiran
0mg placebo injection solution for subcutaneous injection on Day 1 and Day 90
Other Names:
  • Placebo s.c.
Placebo Comparator: Placebo
Placebo s.c. and Placebo p.o.
Drug: Matching Placebo for Ezetimibe
0mg over-encapsulated placebo tablet taken once a day from Day 1 through Day 149
Other Names:
  • Placebo p.o.
Drug: Matching Placebo for Inclisiran
0mg placebo injection solution for subcutaneous injection on Day 1 and Day 90
Other Names:
  • Placebo s.c.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, Day 150

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, Day 150
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.
Baseline, Day 150
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.
Baseline, Day 150
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
Baseline, Day 150
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.
Baseline, Day 150
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.
Baseline, Day 150
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.
Baseline, Day 150
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.
From first dose of study treatment on Day 1 up to Day 180

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2023

Primary Completion (Actual)

June 20, 2024

Study Completion (Actual)

June 20, 2024

Study Registration Dates

First Submitted

February 28, 2023

First Submitted That Met QC Criteria

February 28, 2023

First Posted (Actual)

March 10, 2023

Study Record Updates

Last Update Posted (Estimated)

October 16, 2025

Last Update Submitted That Met QC Criteria

October 8, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CKJX839D12304

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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