Study to understand if inclisiran is better than a placebo at lowering LDL-cholesterol, is safe and can have an impact on patient quality of life, when given along with other lipid lowering medications.

Phase 1

• Conditions: Hypercholesterolemia; MedDRA version: 21.0Level: LLTClassification code 10020604Term: HypercholesterolemiaSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2021-003759-40-BG
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-03-28
• Last Update Posted: 19 February 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1760

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 <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 cardiovascular disease (CVD).
? 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:
? 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.
? 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 <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.

? LDL-C levels at screening and baseline:
? 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 at screening.
? Participants on the individual MTD of statin for = 30 days at baseline.
? Fasting triglyceride < 400 mg/dL at screening and baseline.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 792
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 968

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified