Hypercholesterolemia MedDRA version: 21.0 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Male or female participants =18 years of age. ? Participants meeting one of the following CV category: ?Very high risk participants with at least one of the following: ? Documented Atherosclerotic cardiovascular disease (ASCVD) i Acute coronary syndrome: Unstable angina or myocardial infarction. ii Stable angina. iii Coronary revascularization. iv Unequivocally documented ASCVD upon prior imaging. v Stroke and TIA. vi 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 310 mg/dL, LDL-C > 190 mg/dL, or blood pressure = 180/110 mmHg ? Pre-existing diagnosis of HeFH without other major risk factors. ? Diabetes Mellitus (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 =65 years) yes F.1.3.1 Number of subjects for this age range 968
Exclusion criteria
Exclusion criteria: ? Participants on more than one other lipid-lowering drug on top of statin at screening visit. ? Participants with a known intolerance to rosuvastatin 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. ? 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. ? Heart failure New York Heart Association (NYHA) class IV at screening or baseline visit ? Pregnant or nursing (lactating) women at screening or baseline visit. ? Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Inclisiran, on top of ongoing individually optimized LLT, compared to placebo, on top of ongoing individually optimized LLT, on reaching a participant's individual LDL-C target as defined in 2019 ESC/EAS guidelines for the management of dyslipidemias (Mach et al 2020);Secondary Objective: Inclisiran, on top of ongoing individually optimized LLT, compared to placebo, on top of ongoing individually optimized LLT, on: •Reducing mean LDL-C levels over the double-blind study period. •Muscle-related adverse events. •Annualized number of days pain is experienced using a pain diary. •Pain-related quality of life at day 360 using the Short-Form Brief Pain Inventory (SF-BPI).;Primary end point(s): Proportion of participants achieving individual LDL-C target (< 55 mg/dL or < 70 mg/dL) at day 90;Timepoint(s) of evaluation of this end point: Day 90 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Relative change (percentage from baseline to mean LDL-C level) over the double-blind treatment period. •Proportion of participants experiencing at least one muscle-related AE as defined in the Standardized MedDRA Queries (SMQ) rhabdomyolysis / myopathy from day 1 to day 360. •Proportion of participants experiencing self-reported pain. Annualized number of days participants experiencing self-reported pain from baseline to day 360. •Change from baseline in SF-BPI pain severity score to day 360 Change from baseline in SF-BPI pain interference score to day 360. Proportion of participants with clinically relevant change in SF-BPI pain severity score from baseline to day 360. Proportion of participants with clinically relevant change in SF-BPI pain interference score from baseline to day 360.;Timepoint(s) of evaluation of this end point: from baseline to day 360 | — |
Countries
Bulgaria, Estonia, Germany, Latvia, Spain
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed