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

NCT06431763 | Completed Phase 4

• 1 other identifier: CKJX839A1DE02
• Study Type: interventional
• Target: 402
• Locations: 1 country
• Sites: 55

Brief 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.

Conditions

Hypercholesterolemia

Keywords

LDL-cholesterol; atherosclerotic cardiovascular disease; Inclisiran; bempedoic acid; BPA; PCSK9 inhibitor; head-to-head comparison

Outcome Measures

Primary Outcomes (1)

• Percent change from baseline in LDL-C levels

  To demonstrate superiority of Inclisiran compared to BPA, in combination with standard of care (maximally tolerated HI statin dose +/- Ezetimibe) in reducing relative LDL-C levels at Day 150.

  Baseline, Day 150

Secondary Outcomes (10)

• Percent change from baseline in LDL-C levels in patients without Ezetimibe

  Baseline, Day 150

• Percent change from baseline in LDL-C levels in patients with Ezetimibe

  Baseline, Day 150

• Number of participants by individual responsiveness

  Day 150

• Absolute change from Baseline in LDL-C

  Day 150

• Percent change from Baseline in LDL-C levels

  Baseline, from Day 30 up to Day 150

Study Arms (2)

Inclisiran

EXPERIMENTAL

Inclisiran treatment on top of background treatment (high intensity statin with/without ezetimibe)

Drug: Inclisiran sodium

Bempedoic acid (BPA)

ACTIVE COMPARATOR

BPA treatment on top of background treatment (high intensity statin with/without ezetimibe)

Drug: BPA

Interventions

Inclisiran sodium DRUG

300 mg s.c. administered at day 1 and day 90

Also known as: PCSK9 inhibitor, siRNA

Inclisiran

BPA DRUG

180 mg daily per oral

Also known as: small molecule, ACL inhibitor

Bempedoic acid (BPA)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fasting LDL-C ≥ 70 mg/dL at screening
• Participants must be on a stable (≥ 4 weeks) and well-tolerated lipid-lowering regimen (with or without Ezetimibe \[10mg\]) that must include a high-intensity statin therapy with either atorvastatin ≥40 mg QD or rosuvastatin ≥20 mg QD in a maximally tolerated or maximally approved dose at screening
• 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, Stable angina, Coronary revascularization, Unequivocally documented ASCVD upon prior imaging, Stroke and Transient Ischaemic Attack (TIA), Peripheral artery disease (PAD)
• Diabetes mellitus (DM) with target organ damage (defined as microalbuminuria, retinopathy, or neuropathy), or at least ≥ 3 major risk factors, 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 risk of 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 risk factor
• 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 to estimate 10-year risk of fatal and non-fatal CVD as defined by the cardiovascular risk categories in the 2019 ESC/EAS guideline (Mach et al 2020), and updated SCORE2 and SCORE2-OP (Hageman et al 2021, de Vries et al 2021, Visseren et al 2021). Further details for documented ASCVD will be provided in the protocol.
• Fasting triglyceride \< 400 mg/dL at screening

You may not qualify if:

• Acute coronary syndrome, ischemic stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease \< 4 months prior to screening visit or V1.
• Planned or expected cardiac, cerebrovascular or peripheral artery surgery or coronary re-vascularization within 6 months after screening visit.
• Heart failure NYHA class IV at screening or V1.
• Participants on more than one other lipid-lowering drug on top of statin at screening visit.
• Previous treatment with a mAb directed towards PCSK9 (e.g., evolocumab, alirocumab) or planned use after screening visit.
• Previous treatment prior to screening with BPA within 90 days
• Previous exposure to Inclisiran or any other non-mAb PCSK9-targeted therapy, either as an investigational or marketed drug.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (55)

Novartis Investigative Site

Mannheim, Baden-Wurttemberg, 68305, Germany

Location

Novartis Investigative Site

Stuttgart, Baden-Wurttemberg, 70376, Germany

Location

Novartis Investigative Site

Lichtenfels, Bavaria, 96215, Germany

Location

Novartis Investigative Site

Muehldorf Am Inn, Bavaria, 84453, Germany

Location

Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

Location

Novartis Investigative Site

Sulzbach-Rosenberg, Bavaria, 92237, Germany

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60389, Germany

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60594, Germany

Location

Novartis Investigative Site

Göttingen, Lower Saxony, 37075, Germany

Location

Novartis Investigative Site

Essen, North Rhine-Westphalia, 45355, Germany

Location

Novartis Investigative Site

Koeln Nippes, North Rhine-Westphalia, 50733, Germany

Location

Novartis Investigative Site

Löhne, North Rhine-Westphalia, 32584, Germany

Location

Novartis Investigative Site

Kaiserslautern, Rhineland-Palatinate, 67655, Germany

Location

Novartis Investigative Site

Dresden, Saxony, 01099, Germany

Location

Novartis Investigative Site

Dresden, Saxony, 01307, Germany

Location

Novartis Investigative Site

Leipzig, Saxony, 04209, Germany

Location

Novartis Investigative Site

Jena, Thuringia, 07740, Germany

Location

Novartis Investigative Site

Aachen, 52074, Germany

Location

Novartis Investigative Site

Bad Homburg, 61348, Germany

Location

Novartis Investigative Site

Bad Krozingen, 79189, Germany

Location

Novartis Investigative Site

Bad Oeynhausen, 32545, Germany

Location

Novartis Investigative Site

Bamberg, 96049, Germany

Location

Novartis Investigative Site

Berlin, 10367, Germany

Location

Novartis Investigative Site

Berlin, 13347, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Bochum, 44789, Germany

Location

Novartis Investigative Site

Bochum, 44791, Germany

Location

Novartis Investigative Site

Bremen, 28277, Germany

Location

Novartis Investigative Site

Dessau, 06846, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Erfurt, 99097, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Essen, 45355, Germany

Location

Novartis Investigative Site

Falkensee, 14612, Germany

Location

Novartis Investigative Site

Gladbeck, 45968, Germany

Location

Novartis Investigative Site

Hamburg, 21109, Germany

Location

Novartis Investigative Site

Hamburg, 22041, Germany

Location

Novartis Investigative Site

Hamburg, 22607, Germany

Location

Novartis Investigative Site

Hoyerswerda, 02977, Germany

Location

Novartis Investigative Site

Kassel, 34121, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Ludwigshafen, 67067, Germany

Location

Novartis Investigative Site

Magdeburg, 39120, Germany

Location

Novartis Investigative Site

Markkleeberg, 04416, Germany

Location

Novartis Investigative Site

Meissen, 01662, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Offenbach, 63065, Germany

Location

Novartis Investigative Site

Papenburg, 26871, Germany

Location

Novartis Investigative Site

Pirna, 01796, Germany

Location

Novartis Investigative Site

Potsdam, 14471, Germany

Location

Novartis Investigative Site

Rüdersdorf, 15562, Germany

Location

Novartis Investigative Site

Saint Ingbert Oberw, 66386, Germany

Location

Novartis Investigative Site

Ulm, 89077, Germany

Location

Novartis Investigative Site

Völklingen, 66333, Germany

Location

MeSH Terms

Conditions

Hypercholesterolemia; Atherosclerosis

Interventions

RNA, Small Interfering

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

RNA, Antisense; Antisense Elements (Genetics); Nucleic Acids, Nucleotides, and Nucleosides; RNA; Nucleic Acids; RNA, Small Untranslated; RNA, Untranslated

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2024
• First Posted: May 29, 2024
• Study Start: June 21, 2024
• Primary Completion: December 1, 2025
• Study Completion: January 2, 2026
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

DE (55)