A Study to Investigate LDL-cholesterol Lowering With Inclisiran Compared to Bempedoic Acid in Patients With Atherosclerotic Cardiovascular Disease.

Last updated: March 13, 2025
Sponsor: Novartis Pharmaceuticals
Overall Status: Active - Recruiting

Phase

4

Condition

Hypercholesterolemia

Atherosclerosis

Vascular Diseases

Treatment

BPA

Inclisiran sodium

Clinical Study ID

NCT06431763
CKJX839A1DE02
  • Ages 18-99
  • All Genders

Study Summary

This study is a phase IV, open-label, randomized study designed to evaluate the efficacy of Inclisiran vs. bempedoic acid (BPA) in 400 adult subjects (≥ 18 years) at very high and high risk for cardiovascular events as defined by the cardiovascular risk categories in the 2019 ESC/EAS guidelines for the management of dyslipidemias (Mach et al 2020) and elevated levels of LDL-C (≥ 70 mg/dL) despite being on a maximally tolerated high-intensity (HI) statin dose (+/- Ezetimibe). Currently, BPA is recommended ahead of injectables by German HTA body (GBA). A head-to-head trial is proposed to provide robust scientific data on the superiority of Inclisiran vs. BPA and to support the early use of Inclisiran.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Fasting LDL-C ≥ 70 mg/dL at screening

  2. Participants must be on a stable (≥ 4 weeks) and well-tolerated lipid-loweringregimen (with or without Ezetimibe [10mg]) that must include a high-intensity statintherapy with either atorvastatin ≥40 mg QD or rosuvastatin ≥20 mg QD in a maximallytolerated or maximally approved dose at screening

  3. Participants categorized as very high or high CV risk, as defined below:

  • Very high risk participants with at least one of the following:

  • Documented ASCVD: ACS: Unstable angina or myocardial infarction, Stableangina, Coronary revascularization, Unequivocally documented ASCVD uponprior imaging, Stroke and Transient Ischaemic Attack (TIA), Peripheralartery disease (PAD)

  • Diabetes mellitus (DM) with target organ damage (defined asmicroalbuminuria, retinopathy, or neuropathy), or at least ≥ 3 major riskfactors, or early onset of Type 1 DM of long duration (< 20 years)

  • A calculated SCORE2 ≥ 7.5 % for age < 50 years; SCORE2 ≥ 10 % for age 50-69 years; SCORE2-OP ≥ 15 % for age ≥ 70 years to estimate 10-year riskof fatal and non-fatal CVD

  • Pre-existing diagnosis of heterozygous familial hyper-cholesterolemia (HeFH) with ASCVD or with another major risk factor OR

  • High risk participants with at least one of the following:

  • Markedly elevated single risk factors, in particular total cholesterol > 310 mg/dL, LDL-C > 190 mg/dL, or blood pressure ≥ 180/110 mmHg

  • Pre-existing diagnosis of HeFH without other major risk factors

  • DM without target organ damage (defined as microalbuminuria, retinopathy,or neuropathy), with DM duration ≥ 10 years or other additional riskfactor

  • Moderate chronic kidney disease (eGFR 30-59 mL/min/1.73m2)

  • A calculated SCORE2 2.5 to < 7.5 % for age < 50 years; SCORE2 5 to < 10 %for age 50-69 years; SCORE2-OP 7.5 to < 15 % for age ≥ 70 years toestimate 10-year risk of fatal and non-fatal CVD as defined by thecardiovascular risk categories in the 2019 ESC/EAS guideline (Mach et al 2020), and updated SCORE2 and SCORE2-OP (Hageman et al 2021, de Vries etal 2021, Visseren et al 2021). Further details for documented ASCVD willbe provided in the protocol.

  1. Fasting triglyceride < 400 mg/dL at screening

Exclusion

Exclusion Criteria:

  1. Acute coronary syndrome, ischemic stroke, peripheral arterial revascularizationprocedure or amputation due to atherosclerotic disease < 4 months prior to screeningvisit or V1.

  2. Planned or expected cardiac, cerebrovascular or peripheral artery surgery orcoronary re-vascularization within 6 months after screening visit.

  3. Heart failure NYHA class IV at screening or V1.

  4. Participants on more than one other lipid-lowering drug on top of statin atscreening visit.

  5. Previous treatment with a mAb directed towards PCSK9 (e.g., evolocumab, alirocumab)or planned use after screening visit.

  6. Previous treatment prior to screening with BPA within 90 days

  7. Previous exposure to Inclisiran or any other non-mAb PCSK9-targeted therapy, eitheras an investigational or marketed drug.

Study Design

Total Participants: 400
Treatment Group(s): 2
Primary Treatment: BPA
Phase: 4
Study Start date:
June 21, 2024
Estimated Completion Date:
September 30, 2025

Study Description

During the screening period study eligibility will be assessed and the participants' individual LDL-C target according to guideline (Mach et al., 2020) will be determined. Among other criteria, at screening, a participant must be on a stable maximally tolerated dose of a HI statin with either atorvastatin ≥40 mg once a day (QD) or rosuvastatin ≥20 mg QD (+/- Ezetimibe [10mg]) for ≥ 4 weeks with which, however, a target LDL-C of < 70 mg/dL is not reached.

During the open-label treatment period, all participants, who fulfill the inclusion/exclusion criteria, will be randomized at V1 (Day 1) in a 1:1 open-label fashion to either Inclisiran sodium 300 mg s.c. (administered at Day 1 and Day 90) or to BPA tablets 180 mg p.o. (given once daily). Participants will be required to maintain their background lipid-lowering treatment (maximally tolerated statin dose +/- Ezetimibe) unchanged for the duration of the study. The end of treatment (EOT) is reached at day 150.

A Safety-Follow-up call will be conducted 30 days after EOT visit (Day 180).

The overall study duration is approximately 190 days but can vary depending on individual screening and the visit windows allowed for the treatment period and EOS visit.

Connect with a study center

  • Novartis Investigative Site

    Konstanz, Baden Wuerttemberg 78464
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Mannheim, Baden Wuerttemberg 68305
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Regensburg, Bavaria 93053
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Frankfurt Am Main, Hessen 60389
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Frankfurt am Main, Hessen 60590
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Goettingen, Niedersachsen 37075
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Kaiserslautern, Rhineland-Palatinate 67655
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Aachen, 52074
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Bad Homburg, 61348
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Bad Krozingen, 79189
    Germany

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  • Novartis Investigative Site

    Bad Oeynhausen, 32545
    Germany

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  • Novartis Investigative Site

    Bamberg, 96049
    Germany

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  • Novartis Investigative Site

    Berlin, 13353
    Germany

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  • Novartis Investigative Site

    Bochum, 44791
    Germany

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  • Novartis Investigative Site

    Bremen, 28277
    Germany

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  • Novartis Investigative Site

    Dessau-Rosslau, 06846
    Germany

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  • Novartis Investigative Site

    Dessau-Roßlau, 06846
    Germany

    Site Not Available

  • Novartis Investigative Site

    Dresden, 01307
    Germany

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  • Novartis Investigative Site

    Erfurt, 99097
    Germany

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  • Novartis Investigative Site

    Essen, 45355
    Germany

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  • Novartis Investigative Site

    Falkensee, 14612
    Germany

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  • Novartis Investigative Site

    Frankfurt, 60389
    Germany

    Site Not Available

  • Novartis Investigative Site

    Gladbeck, 45968
    Germany

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  • Novartis Investigative Site

    Gottingen, 37075
    Germany

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  • Novartis Investigative Site

    Greifswald, 17475
    Germany

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  • Novartis Investigative Site

    Guetersloh, 33332
    Germany

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  • Novartis Investigative Site

    Hamburg, 22041
    Germany

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  • Novartis Investigative Site

    Hannover, 30625
    Germany

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  • Novartis Investigative Site

    Herne, 44625
    Germany

    Site Not Available

  • Novartis Investigative Site

    Hoyerswerda, 02977
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Jena, 07740
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Kassel, 34121
    Germany

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  • Novartis Investigative Site

    Kiel, 24105
    Germany

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  • Novartis Investigative Site

    Koeln-Nippes, 50733
    Germany

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  • Novartis Investigative Site

    Leipzig, 04209
    Germany

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  • Novartis Investigative Site

    Lichtenfels, 96215
    Germany

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  • Novartis Investigative Site

    Loehne, 32584
    Germany

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  • Novartis Investigative Site

    Ludwigshafen, 67067
    Germany

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  • Novartis Investigative Site

    Magdeburg, 39120
    Germany

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  • Novartis Investigative Site

    Markkleeberg, 04416
    Germany

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  • Novartis Investigative Site

    Meissen, 01662
    Germany

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  • Novartis Investigative Site

    Muehldorf, 84453
    Germany

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  • Novartis Investigative Site

    Muenster, 48149
    Germany

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  • Novartis Investigative Site

    Offenbach Am Main, 63065
    Germany

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  • Novartis Investigative Site

    Papenburg, 26871
    Germany

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  • Novartis Investigative Site

    Pirna, 01796
    Germany

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  • Novartis Investigative Site

    Potsdam, 14471
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Ruedersdorf, 15562
    Germany

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  • Novartis Investigative Site

    Saint Ingbert Oberwuerzbach, 66386
    Germany

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  • Novartis Investigative Site

    Stuttgart, 70376
    Germany

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  • Novartis Investigative Site

    Sulzbach Rosenberg, 92237
    Germany

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  • Novartis Investigative Site

    Ulm, 89077
    Germany

    Active - Recruiting

  • Novartis Investigative Site

    Voelklingen, 66333
    Germany

    Active - Recruiting

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