Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05192941
Other study ID # CKJX839A12402
Secondary ID 2021-003759-40
Status Active, not recruiting
Phase Phase 4
First received
Last updated
Start date April 8, 2022
Est. completion date March 4, 2025

Study information

Verified date February 2024
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


Description:

The purpose of this study is to demonstrate the superiority of inclisiran compared to placebo, both on top of ongoing individually optimized lipid-lowering therapy (LLT), on reaching a participant's LDL-C target (< 55 mg/dL or < 70 mg/dL, depending on the cardiovascular risk category, according to the 2019 ESC/EAS guidelines for the management of dyslipidemias as well as on patient-relevant safety, tolerability outcomes and quality of life.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 1772
Est. completion date March 4, 2025
Est. primary completion date March 4, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 99 Years
Eligibility Key Inclusion Criteria: Participants eligible for inclusion in this study must meet all of the following criteria: 1. Written informed consent must be obtained before any assessment is performed. 2. Male or female participants =18 years of age. 3. 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. OR •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) 4. LDL-C levels: 1. in participants with very high cardiovascular risk: serum LDL-C =55 mg/dL 2. in participants with high cardiovascular risk: serum LDL-C =70 mg/dL 5. Participant on a stable dose of a statin for = 30 days. 6. 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. 7. Fasting triglyceride < 400 mg/dL. At Baseline: 8. Fasting triglyceride < 400 mg/dL. 9. 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), 1. in participants with very high cardiovascular risk: serum LDL-C = 55mg/dL. 2. in participants with high cardiovascular risk: serum LDL-C = 70mg/dL. Key Exclusion Criteria: Participants meeting any of the following criteria are not eligible for inclusion in this study. 1. Severe concomitant non-CV disease that is expected to reduce life expectancy to less than 2 years at screening or baseline visit. 2. Participants on more than one other lipid-lowering drug on top of statin at screening visit. 3. Pre-existing diagnosis of homozygous familial hypercholesterolemia at screening or baseline visit. 4. Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome at screening or baseline visit. 5. 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. 6. 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. 7. Previous, current or planned treatment with LDL-apheresis at screening or baseline visit. 8. Participants with known intolerance to rosuvastatin at screening or baseline visit. 9. 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. 10. Participants taking gemfibrozil at screening or baseline visit. 11. 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. 12. 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. 13. 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. 14. Planned or expected cardiac, cerebrovascular or peripheral artery surgery or coronary revascularization within the study duration. 15. Heart failure New York Heart Association (NYHA) class IV at screening or baseline visit. 16. History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy (excluding systemic adjuvant therapies given to prevent cancer recurrence eg: hormonotherapy for prostate or breast cancer) during the 3 years prior to screening or baseline visit. 17. Participant with myopathy at screening or baseline visit. 18. Participant receiving concomitant ciclosporin at screening or baseline visit. 19. Participants that are predisposed to the development of renal failure secondary to rhabdomyolysis (e.g. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures). 20. Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose-malabsorption. 21. Unwillingness or inability (e.g. physical or cognitive) to comply with study procedures (including study visits, fasting blood draws and compliance with study treatment regimens), and medication administration (injections) and schedule. Participant should be able and willing to read, understand and answer questionnaires. 22. Any surgical or medical condition, which in the opinion of the investigator, may place the participant at higher risk from his/her participation in the study, or is likely to prevent the participant from complying with the requirements of the study or completing the study at screening or baseline visit. 23. Use of other investigational drugs within 5 half-lives, 30 days or until the expected pharmacodynamic effect has returned to baseline (e.g. biologics), whichever is longer or longer if required by local regulation, prior to screening visit. 24. Pregnant or nursing (lactating) women at screening or baseline visit. 25. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment, which includes rosuvastatin, and for 5 days (= 5 times the terminal half-life of rosuvastatin) after stopping medication. Highly effective contraception methods include: - Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. - Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. - Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant. - Use of oral, (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). Women are considered not of child bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessments and she is considered not of child bearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the local ICF.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Inclisiran Sodium
Subcutaneously injected on Day 1, Day 90, and Day 270
Placebo
Placebo to inclisiran 300 mg subcutaneously

Locations

Country Name City State
Bulgaria Novartis Investigative Site Burgas
Bulgaria Novartis Investigative Site Gabrovo
Bulgaria Novartis Investigative Site Pleven
Bulgaria Novartis Investigative Site Plovdiv
Bulgaria Novartis Investigative Site Ruse
Bulgaria Novartis Investigative Site Sofia
Bulgaria Novartis Investigative Site Sofia
Bulgaria Novartis Investigative Site Sofia
Bulgaria Novartis Investigative Site Sofia
Bulgaria Novartis Investigative Site Stara Zagora
Bulgaria Novartis Investigative Site Varna
Bulgaria Novartis Investigative Site Veliko Tarnovo
Czechia Novartis Investigative Site Chlumec nad Cidlinou
Czechia Novartis Investigative Site Hlucin
Czechia Novartis Investigative Site Hodonin
Czechia Novartis Investigative Site Melnik
Czechia Novartis Investigative Site Olomouc
Czechia Novartis Investigative Site Olomouc
Czechia Novartis Investigative Site Pardubice Czech Republic
Czechia Novartis Investigative Site Prerov Olomoucky Kraj
Czechia Novartis Investigative Site Slany
Czechia Novartis Investigative Site Trutnov CZE
Estonia Novartis Investigative Site Parnu
Estonia Novartis Investigative Site Tallinn
Estonia Novartis Investigative Site Tallinn
Estonia Novartis Investigative Site Tartu
France Novartis Investigative Site Amiens Cedex 1
France Novartis Investigative Site Chambéry cedex
France Novartis Investigative Site Le Chesnay
France Novartis Investigative Site Le Kremlin Bicetre
France Novartis Investigative Site Lille
France Novartis Investigative Site Marseille
France Novartis Investigative Site Paris 13
France Novartis Investigative Site St Herblain
France Novartis Investigative Site Valenciennes
Germany Novartis Investigative Site Bad Gottleuba Sachsen
Germany Novartis Investigative Site Bad Homburg
Germany Novartis Investigative Site Bad Krozingen
Germany Novartis Investigative Site Bad Oeynhausen
Germany Novartis Investigative Site Bamberg
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Bochum
Germany Novartis Investigative Site Bremen
Germany Novartis Investigative Site Coburg
Germany Novartis Investigative Site Dessau-Roßlau
Germany Novartis Investigative Site Dresden
Germany Novartis Investigative Site Dresden Saxonia
Germany Novartis Investigative Site Duisburg
Germany Novartis Investigative Site Erfurt
Germany Novartis Investigative Site Erfurt
Germany Novartis Investigative Site Essen
Germany Novartis Investigative Site Essen
Germany Novartis Investigative Site Essen
Germany Novartis Investigative Site Frankfurt
Germany Novartis Investigative Site Frankfurt
Germany Novartis Investigative Site Frankfurt
Germany Novartis Investigative Site Fulda
Germany Novartis Investigative Site Gelnhausen
Germany Novartis Investigative Site Gladbeck
Germany Novartis Investigative Site Gottingen
Germany Novartis Investigative Site Hamburg
Germany Novartis Investigative Site Hamburg
Germany Novartis Investigative Site Hannover Niedersachsen
Germany Novartis Investigative Site Hannover Niedersachsen
Germany Novartis Investigative Site Hassloch
Germany Novartis Investigative Site Hennigsdorf
Germany Novartis Investigative Site Hoyerswerda
Germany Novartis Investigative Site Kaiserslautern Rhineland-Palatinate
Germany Novartis Investigative Site Kassel
Germany Novartis Investigative Site Kiel
Germany Novartis Investigative Site Koeln
Germany Novartis Investigative Site Koln
Germany Novartis Investigative Site Langen
Germany Novartis Investigative Site Leipzig
Germany Novartis Investigative Site Lichtenfels
Germany Novartis Investigative Site Loehne
Germany Novartis Investigative Site Lüneburg
Germany Novartis Investigative Site Magdeburg
Germany Novartis Investigative Site Magdeburg
Germany Novartis Investigative Site Mainz
Germany Novartis Investigative Site Mannheim
Germany Novartis Investigative Site Mannheim Baden Wuerttemberg
Germany Novartis Investigative Site Markkleeberg
Germany Novartis Investigative Site Muehldorf
Germany Novartis Investigative Site Muenchen
Germany Novartis Investigative Site Muenster
Germany Novartis Investigative Site Nuremberg
Germany Novartis Investigative Site Papenburg
Germany Novartis Investigative Site Pirna
Germany Novartis Investigative Site Potsdam
Germany Novartis Investigative Site Regensburg Bavaria
Germany Novartis Investigative Site Reinfeld
Germany Novartis Investigative Site Rostock
Germany Novartis Investigative Site Rüdersdorf
Germany Novartis Investigative Site Saint Ingbert - Oberwuerzbach
Germany Novartis Investigative Site Schleswig Schleswig-Holstein
Germany Novartis Investigative Site Singen
Germany Novartis Investigative Site Stuttgart
Germany Novartis Investigative Site Stuttgart
Germany Novartis Investigative Site Wallerfing
Germany Novartis Investigative Site Warendorf
Germany Novartis Investigative Site Winsen Lower Saxony
Germany Novartis Investigative Site Wuppertal
Latvia Novartis Investigative Site Daugavpils
Latvia Novartis Investigative Site Ogre
Latvia Novartis Investigative Site Riga
Latvia Novartis Investigative Site Riga
Latvia Novartis Investigative Site Riga
Latvia Novartis Investigative Site Riga
Poland Novartis Investigative Site Gdynia
Poland Novartis Investigative Site Katowice
Poland Novartis Investigative Site Krakow
Poland Novartis Investigative Site Krakow Maloposkie
Poland Novartis Investigative Site Krosno
Poland Novartis Investigative Site Rzeszow
Poland Novartis Investigative Site Skierniewice
Poland Novartis Investigative Site Szczecin Zachodniopomorskie
Poland Novartis Investigative Site Tarnow Malopolskie
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Cordoba Andalucia
Spain Novartis Investigative Site Madrid
Spain Novartis Investigative Site Malaga Andalucia
Spain Novartis Investigative Site Oviedo Asturias
Spain Novartis Investigative Site San Sebastian de los Reyes Madrid
Spain Novartis Investigative Site Sanlucar de Barrameda Andalucia
Spain Novartis Investigative Site Sevilla Andalucia
Spain Novartis Investigative Site Sevilla Andalucia

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Estonia,  France,  Germany,  Latvia,  Poland,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Proportion of participants achieving individual LDL-C target (<55 mg/dL or <70 mg/dL) Inclisiran on top of ongoing individually optimized lipid-lowering therapy (LLT) compared to placebo on top of ongoing individually optimized LLT on reaching a participant's individual LDL-C target as measured by the proportion of participants achieving individual LDL-C target (<55mg/dL or < 70 mg/dL) at day 90. Day 90
Secondary Relative percentage change from baseline to mean LDL-C level over the double-blind treatment period Inclisiran on top of ongoing individually optimized LLT compared to placebo on top of ongoing individualized LLT on: reducing mean LDL-C levels over the double-blind study period. Baseline to Day 360
Secondary Proportion of participants experiencing at least one Muscle-related adverse event (AE) as defined in the Standardized MedDRA Queries (SMQ) Participants experiencing at least one muscle-related AE as defined in the SMQ rhabdomyolysis/myopathy from day 1 to day 360. Baseline to Day 360
Secondary Proportion of participants experiencing self-reported pain Annualized number of days pain is experienced using pain diary Baseline to Day 360
Secondary Change from baseline in Short-Form Brief Pain Inventory (SF-BPI) pain severity score to Day 360 Pain-related quality of life at day 360 using the SF-BPI Baseline to Day 360
Secondary Change from baseline in Short-Form Brief Pain Inventory (SF-BPI) pain interference score at Day 360 Pain related quality of life at day 360 using the SF-BPI Baseline to day 360
Secondary Proportion of participants with clinically relevant change in Short-Form Brief Pain Inventory (SF-BPI) pain severity score from baseline to day 360. Pain-related quality of life at day 360 using the SF-BPI Baseline to Day 360
Secondary Proportion of participants with clinically relevant change in Short-Form Brief Pain Inventory (SF-BPI) pain interference score from baseline to day 360 Pain-related quality of life at day 360 using the SF-BPI Baseline to Day 360
See also
  Status Clinical Trial Phase
Completed NCT04998695 - Health Effects of Consuming Olive Pomace Oil N/A
Recruiting NCT03947866 - Ezetimibe-Rosuvastatin Evaluation Study
Completed NCT01709513 - Study of Alirocumab (REGN727/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular (CV) Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE) Phase 3
Completed NCT01212900 - Randomized Trial of Imaging Versus Risk Factor-Based Therapy for Plaque Regression Phase 4
Completed NCT00001154 - Lipoprotein Metabolism in Normal Volunteers and Patients With High Levels of Lipoproteins
Completed NCT02550288 - A Clinical Trial to Assess the Efficacy and Safety of MK-0653C in Japanese Participants With Hypercholesterolemia (MK-0653C-383) Phase 3
Completed NCT03929198 - Translation of Pritikin Program to the Community N/A
Completed NCT04485793 - Effect of a Dietary Supplement on Lipid Pattern and Liver Parameters in Hypercholesterolemia N/A
Completed NCT02341924 - Validating the "Foods for Health" Portfolio of Functional Food Products N/A
Active, not recruiting NCT02223793 - Vascular Lifestyle-Intervention and Screening in Pharmacy N/A
Completed NCT01941836 - Evaluation of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic Patients Phase 2
Completed NCT01934608 - The Effect of Synching Prescription Refills on Adherence N/A
Recruiting NCT01705873 - Analysis on the Risk of Cardiovascular Events in HIV- Infected Subjects Treated With LPV/r Based HAART Regimen vs. an EFV Based Regimen N/A
Completed NCT01678521 - Effect of LDL-apheresis on PTX3 Plasma Levels in Hypercholesterolemic Patients N/A
Completed NCT01670734 - Pharmacokinetic and Tolerability of Alirocumab SAR236553 (REGN727) in Patients With Hepatic Impairment and in Healthy Subjects Phase 1
Completed NCT01370603 - A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/40 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 40 mg Tablets in Participants With High Cholesterol (MK-0653C-190 AM1) Phase 3
Completed NCT01370590 - A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/20 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 20 mg Tablets in Participants With High Cholesterol (MK-0653C-185 AM1) Phase 3
Completed NCT01478789 - Efficacy of Plant Sterol-Fortified Dairy Product on Plasma Lipid and Plant Sterol Concentrations in Humans N/A
Completed NCT01575171 - Using Nudges to Implement Comparative Effectiveness N/A
Completed NCT01446679 - Special Drug Use-Results Survey of Lipitor Tablets N/A