Study of Efficacy, Safety, Tolerability and Quality of Life of Inclisiran (KJX839) vs Placebo, on Top of Ongoing Individually Optimized Lipid-lowering Therapy, in Participants With Hypercholesterolemia

NCT05192941 | Completed Phase 4 Results

• 2 other identifiers: CKJX839A124022024-511263-28
• Study Type: interventional
• Target: 1,770
• Locations: 7 countries
• Sites: 126

Brief Summary

Study of efficacy, safety, tolerability and quality of life of inclisiran (KJX839) vs placebo, on top of ongoing individually optimized lipid-lowering therapy, in participants with hypercholesterolemia

Conditions

Hypercholesterolemia

Keywords

Inclisiran; rosuvastatin; PCSK9; dyslipidemia; angina pectoris; peripheral artery disease; cardiovascular disease; LDL-C

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving Individual LDL-C Target (<55 mg/dL or <70 mg/dL)

  Number of participants achieving individual Low-density Lipoprotein Cholesterol (LDL-C) target (\< 55 mg/dL or \< 70 mg/dL) at Day 90. The individual LDL-C target of the participants was determined according to their most recent individual cardiovascular risk category. A larger proportion of participants indicates a superior outcome.

  Day 90

Secondary Outcomes (8)

• Relative Change From Baseline to Mean LDL-C Level Over the Double-blind Treatment Period

  Baseline to Day 360

• Number of Participants Experiencing at Least One Muscle-related Adverse Event From Day 1 to Day 360

  Day 1 to Day 360

• Number of Participants Experiencing Self-reported Pain

  Day 1 to Day 360

• Annualized Number of Days With Pain

  Day 1 to Day 360

• Average Absolute Change From Baseline in Short-Form Brief Pain Inventory (SF-BPI) Pain Severity Score Over the Double-blind Treatment Period

  Baseline to Day 360

Study Arms (2)

Inclisiran

EXPERIMENTAL

Inclisiran sodium 300 mg s.c. + open label rosuvastatin Open label study treatment rosuvastatin: participants receive an individually optimized rosuvastatin therapy for reaching the individual LDL-C target and tolerability

Drug: Inclisiran Sodium

Placebo

PLACEBO COMPARATOR

Corresponding placebo + open label rosuvastatin Open label study treatment rosuvastatin: participants receive an individually optimized rosuvastatin therapy for reaching the individual LDL-C target and tolerability

Drug: Placebo

Interventions

Inclisiran Sodium DRUG

Subcutaneously injected on Day 1, Day 90, and Day 270

Also known as: KJX839

Inclisiran

Placebo DRUG

Placebo to inclisiran 300 mg subcutaneously

Placebo

Eligibility Criteria

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

You may qualify if:

• Written informed consent must be obtained before any assessment is performed.
• Male or female participants ≥18 years of age.
• Participants categorized as very high or high CV risk, as defined below:
• Very high risk participants with at least one of the following: A. Documented Atherosclerotic Cardiovascular Disease (ASCVD) i) Acute Coronary Syndrome: Unstable angina or myocardial infarction ii) Stable angina iii) Unequivocally documented ASCVD upon prior imaging v) Stroke and Transient Ischaemic Attack (TIA) vi) Peripheral Artery Disease (PAD) B. 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) C. 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 D. Pre-existing diagnosis of heterozygous familial hypercholesterolemia (HeFH) with ASCVD or with another major risk factor.
• High risk participants with at least one of the following: A. Markedly elevated single risk factors, in particular total cholesterol \> 310 mg/dL, LDL-C \> 190 mg/dL, or blood pressure ≥ 180/110 mmHg B. Pre-existing diagnosis of HeFH without other major risk factors C. DM without target organ damage (defined as microalbuminuria, retinopathy, or neuropathy), with DM duration ≥ 10 years or other additional risk factor D. Moderate chronic kidney disease (eGFR 30-59 mL/min/1.73m2) E. A calculated SCORE2 2.5 to \<7.5% for age under 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)
• LDL-C levels:
• in participants with very high cardiovascular risk: serum LDL-C ≥55 mg/dL
• in participants with high cardiovascular risk: serum LDL-C ≥70 mg/dL
• Participant on a stable dose of a statin for ≥ 30 days.
• Up to approximately 20% of total participants can be on a stable dose (for ≥ 30 days prior to screening) of another LLT on top of statin such as a cholesterol absorbing inhibitor or a bile acid sequestrant, or alternatively, an adenosine triphosphate citrate lyase (ACL) inhibitor, as indicated.
• Fasting triglyceride \< 400 mg/dL.
• At Baseline:
• Fasting triglyceride \< 400 mg/dL.
• Before randomization, despite being treated with the individual MTD of a statin for ≥ 30 days and, if applicable, with another LLT on top of statin (stable for ≥ 30 days),
• in participants with very high cardiovascular risk: serum LDL-C ≥ 55mg/dL.

You may not qualify if:

• Severe concomitant non-CV disease that is expected to reduce life expectancy to less than 2 years at screening or baseline visit.
• Participants on more than one other lipid-lowering drug on top of statin at screening visit.
• Pre-existing diagnosis of homozygous familial hypercholesterolemia at screening or baseline visit.
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome at screening or baseline visit.
• Previous (within 90 days of screening), current or planned treatment with a monoclonal antibody (mAb) directed towards PCSK9 (e.g. evolocumab, alirocumab) at screening or baseline visit.
• Previous exposure to inclisiran or any other non-mAb PCSK9 targeted therapy, either as an investigational or marketed drug within 2 years prior to screening or baseline visit.
• Previous, current or planned treatment with LDL-apheresis at screening or baseline visit.
• Participants with known intolerance to rosuvastatin at screening or baseline visit.
• History of hypersensitivity to any of the study treatments, inclisiran or rosuvastatin, or its excipients or to drugs of similar chemical classes at screening or baseline visit.
• Participants taking gemfibrozil at screening or baseline visit.
• Liver and CK: (a) Active liver disease defined as any current infectious, neoplastic, or metabolic pathology of the liver or (b) unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation \>3x ULN, or total bilirubin elevation \> 2x ULN (except for participants with Gilbert's syndrome), or (c) creatine kinase (CK) \>5x ULN at screening or baseline visit.
• Participant with severe renal impairment defined by eGFR \<30 mL/min/1.73m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula at screening or baseline visit.
• Acute coronary syndrome, ischemic stroke or TIA, coronary revascularization or peripheral arterial revascularization procedure or amputation due to atherosclerotic disease \< 3 months prior to the screening or baseline visit.
• Planned or expected cardiac, cerebrovascular or peripheral artery surgery or coronary revascularization within the study duration.
• Heart failure New York Heart Association (NYHA) class IV at screening or baseline visit.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (136)

Novartis Investigative Site

Sofia, Bulgaria, 1202, Bulgaria

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Burgas, Burgas, 8000, Bulgaria

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Burgas, 8001, Bulgaria

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Gabrovo, 5300, Bulgaria

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Pleven, 5800, Bulgaria

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Plovdiv, 4002, Bulgaria

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Rousse, 7000, Bulgaria

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Sofia, 1233, Bulgaria

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Sofia, 1606, Bulgaria

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Sofia, 1618, Bulgaria

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Stara Zagora, 6000, Bulgaria

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Varna, 9010, Bulgaria

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Veliko Tarnovo, 5000, Bulgaria

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Novartis Investigative Site

Chlumec nad Cidlinou, Chlumec Nad Cidlinou, 503 51, Czechia

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Novartis Investigative Site

Přerov, Olomoucký kraj, 750 02, Czechia

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Novartis Investigative Site

Hlučín, 748 01, Czechia

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Hodonín, 695 01, Czechia

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Mělník, 276 01, Czechia

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Olomouc, 772 00, Czechia

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Olomouc, 779 00, Czechia

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Pardubice, 532 03, Czechia

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Slaný, 274 01, Czechia

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Trutnov, 460 63, Czechia

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Pärnu, 80018, Estonia

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Tallinn, 10138, Estonia

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Tallinn, 13419, Estonia

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Tartu, 50406, Estonia

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Amiens, 80054, France

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Chambéry, 73000, France

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Le Chesnay, 78150, France

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Le Kremlin-Bicêtre, 94275, France

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Lille, 59000, France

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Marseille, 13005, France

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Nantes, 44093, France

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Paris, 75013, France

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Valenciennes, 59300, France

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Mannheim, Baden-Wurttemberg, 68305, Germany

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Stuttgart, Baden-Wurttemberg, 70376, Germany

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Lichtenfels, Bavaria, 96215, Germany

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Muehldorf Am Inn, Bavaria, 84453, Germany

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Munich, Bavaria, 81377, Germany

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Nuremberg, Bavaria, 90402, Germany

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Regensburg, Bavaria, 93053, Germany

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Frankfurt am Main, Hesse, 60590, Germany

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Frankfurt am Main, Hesse, 60594, Germany

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Frankfurt am Main, Hesse, 65929, Germany

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Langen, Hesse, 63225, Germany

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Göttingen, Lower Saxony, 37075, Germany

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Hanover, Lower Saxony, 30159, Germany

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Hanover, Lower Saxony, 30449, Germany

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Winsen, Lower Saxony, 21423, Germany

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Cologne, North Rhine-Westphalia, 51065, Germany

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Essen, North Rhine-Westphalia, 45355, Germany

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Löhne, North Rhine-Westphalia, 32584, Germany

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Kaiserslautern, Rhineland-Palatinate, 67655, Germany

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Saint Ingbert, Saarland, 66386, Germany

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Bad Gottleuba, Saxony, 01816, Germany

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Dresden, Saxony, 01099, Germany

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Dresden, Saxony, 01307, Germany

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Leipzig, Saxony, 04103, Germany

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Schleswig, Schleswig-Holstein, 24837, Germany

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Bad Homburg, 61348, Germany

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Bad Krozingen, 79189, Germany

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Bad Oeynhausen, 32545, Germany

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Bamberg, 96049, Germany

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Berlin, 10367, Germany

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Berlin, 10559, Germany

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Berlin, 10787, Germany

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Berlin, 10789, Germany

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Berlin, 13347, Germany

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Berlin, 13353, Germany

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Bochum, 44789, Germany

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Bremen, 28277, Germany

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Coburg, 96450, Germany

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Cologne, 51069, Germany

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Dessau, 06846, Germany

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Dresden, 01307, Germany

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Duisburg, 47051, Germany

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Erfurt, 99089, Germany

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Erfurt, 99097, Germany

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Essen, 45277, Germany

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Essen, 45355, Germany

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Essen, 45359, Germany

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Fulda, 36037, Germany

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Gelnhausen, 63571, Germany

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Gladbeck, 45968, Germany

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Hamburg, 22041, Germany

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Hamburg, 22607, Germany

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Haßloch, 67454, Germany

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Hennigsdorf, 16761, Germany

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Hoyerswerda, 02977, Germany

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Kassel, 34121, Germany

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Kiel, 24105, Germany

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Lüneburg, 21339, Germany

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Magdeburg, 39110, Germany

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Magdeburg, 39120, Germany

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Mainz, 55131, Germany

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Mannheim, 68165, Germany

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Markkleeberg, 04416, Germany

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Münster, 48149, Germany

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Papenburg, 26871, Germany

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Pirna, 01796, Germany

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Potsdam, 14471, Germany

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Reinfeld, 23858, Germany

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Rostock, 18057, Germany

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Rüdersdorf, 15562, Germany

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Singen, 78224, Germany

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Stuttgart, 70378, Germany

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Wallerfing, 94574, Germany

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Warendorf, 48231, Germany

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Wuppertal, 42117, Germany

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Daugavpils, LV-5417, Latvia

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Ogre, 5001, Latvia

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Riga, 1012, Latvia

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Riga, LV 1002, Latvia

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Riga, LV-1001, Latvia

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Riga, LV-1012, Latvia

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Krosno, Krosno, 38-400, Poland

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Krakow, Maloposkie, 31-271, Poland

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Szczecin, West Pomeranian Voivodeship, 71-528, Poland

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Gdynia, 81-157, Poland

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Katowice, 40-648, Poland

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Krakow, 31-216, Poland

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Rzeszów, 35-055, Poland

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Skierniewice, 96-100, Poland

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Tarnów, 33-100, Poland

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Málaga, Andalusia, 29009, Spain

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Seville, Andalusia, 41014, Spain

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Sanlucar Barrameda, Cadiz, 11540, Spain

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Barcelona, Catalonia, 08003, Spain

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Majadahonda, Madrid, 28222, Spain

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San Sebastian Reyes, Madrid, 28702, Spain

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Oviedo, Principality of Asturias, 33011, Spain

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Barcelona, 08035, Spain

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Córdoba, 14004, Spain

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Novartis Investigative Site

Seville, 41013, Spain

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Related Publications (1)

• Landmesser U, Laufs U, Schatz U, Winzer EB, Nowak B, Kassner U, Gouni-Berthold I, Esteban A, Lubyayi L, Krueger A, Streich JH, Hentschke C, Achouba A, Banach M. Design and rationale of the VICTORION-Difference study: A phase 4 randomized, double-blind, placebo-controlled clinical trial to assess inclisiran's early efficacy, safety, tolerability, as well as its impact on quality of life in individuals with hypercholesterolemia. Am Heart J. 2025 Nov;289:117-126. doi: 10.1016/j.ahj.2025.05.014. Epub 2025 May 26.

  PMID: 40436308 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia; Dyslipidemias; Angina Pectoris; Peripheral Arterial Disease; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Hyperlipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Myocardial Ischemia; Heart Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

1-888-669-6682

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants were randomized at the baseline visit (Day 1) to one of the following two double-blind treatment groups in a 1:1 ratio. 1. Inclisiran sodium 300 mg s.c. 2. Corresponding placebo Each participant received one injection of blinded inclisiran or placebo on Day 1, a second injection of blinded inclisiran or placebo on Day 90 and a subsequent injection of blinded inclisiran or placebo on Day 270, unless there was a need for discontinuing inclisiran/placebo in the course of the study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind investigational treatment inclisiran/placebo: subcutaneous injections of inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) or placebo, in 1.5 mL solution. Open label study treatment rosuvastatin: all participants received rosuvastatin, starting at the lowest indicated dose and titrating up until they reach their individual LDL-C target or MTD (Maximum tolerated dose) of statin, whichever occurs first.

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: January 14, 2022
• Study Start: April 8, 2022
• Primary Completion: June 11, 2024
• Study Completion: March 19, 2025
• Last Updated: April 14, 2026
• Results First Posted: April 14, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

ES (4); CZ (10); DE (75); LA (6); PL (9); FR (9); BU (13)