Atherosclerotic Cardiovascular Disease
Conditions
Keywords
Atherosclerotic cardiovascular disease, Hypercholesterolemia, Dyslipidemia, High cholesterol, Hyperlipidemia, Inclisiran, siRNA, KJX839, Myocardial infarction, Ischemic stroke, Peripheral arterial disease, In silico model, In silico simulation, PCSK9 inhibitors, Arteriosclerosis, Atherosclerosis, Arterial Occlusive Diseases, Vascular Diseases, Cardiovascular Diseases
Brief summary
Study CKJX839B1FR01 in an In silico trial to predict the efficacy of Inclisiran therapy on major adverse cardiovascular events (MACE) and cardiovascular (CV) death in virtual patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C.
Detailed description
Purpose of this study is to predict the size of efficacy of inclisiran 300 mg s.c., administered on Day 1, Month 3 (Day 90), and every 6 months thereafter in addition to currently available lipid lowering therapies (LLTs) on a 3-Point-Major Adverse Cardiovascular Events (3P-MACE) defined as a composite of CV death, non-fatal myocardial infarction (MI) or non-fatal ischemic stroke, and on CV death, in a secondary prevention cohort of ASCVD virtual patients with a LDL-C ≥ 70 mg/dL. This will be compared to 1) placebo in adjunct to high-intensity statin therapy with or without ezetimibe, 2) ezetimibe in adjunct to high-intensity statin therapy, 3) Evolocumab in adjunct to high-intensity statin therapy and ezetimibe.
Interventions
Drug: Inclisiran sodium 300 mg virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.
DRUGPlacebo
Drug: Placebo virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.
DRUGEzetimibe
Drug: Ezetimibe 10 mg virtually orally once a day until end of simulation.
DRUGEvolocumab
Drug: Evolocumab 140 mg virtually subcutaneously administered every two weeks until end of simulation.
Sponsors
Novartis Pharmaceuticals
Study design
Observational model
OTHER
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
: 1. Patients with atherosclerotic CV disease, defined as any of the following i. Previous MI ii. Previous ischemic stroke iii. Previous symptomatic peripheral arterial disease (PAD) as evidenced by either intermittent claudication with ABI \<0.85, prior peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease 2. Fasting LDL-C ≥ 70 mg/dL 3. Under stable (≥ 4 weeks) well-tolerated high-intensity statin with or without ezetimibe.
Exclusion criteria
: Patients with acute coronary syndrome, ischemic stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease \<4 weeks prior to the first study visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to the first occurrence between trial start and end of follow-up of any component of 3P-MACE (composite of CV death, non-fatal MI or non-fatal ischemic stroke) | 5 years of follow-up | 3P-MACE is a confirmed composite endpoint which includes cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke. |
| Time to the first occurrence between trial start and end of follow-up of CV death | 5 years of follow-up | CV death is defined as death due to cardiovascular events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to the first occurrence between trial start and end of follow-up of MI (non-fatal or fatal) | 5 years of follow-up | Myocardial infarction (MI) |
| Time to the first occurrence between trial start and end of follow-up of ischemic stroke (non-fatal or fatal) | 5 years of follow-up | — |
| Time to the first occurrence between trial start and end of follow-up of Major Adverse Limb events (MALE) | 5 years of follow-up | MALE include acute lower limb ischemia, lower limb amputation due to ischemia, or urgent lower limb revascularization for ischemia |
| Change in LDL-C from baseline to specified time points | baseline, day 1, 30, 90 and every 6 months afterwards will be presented and additional time points could be added if deemed necessary. | Low density lipoprotein cholesterol (LDL-C) |
| Time adjusted percentage change in LDL-C | From baseline between Day 90 and the end of follow-up period (up to 5 years) | This is the average percentage change in LDL-C from baseline over period from Day 90 and the end of follow-up period. |
Countries
France
Outcome results
None listed