In Silico Study Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in French Patients With Established Cardiovascular Disease

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05974345

Collaborator

(none)

54,724

Enrollment

3.1

Anticipated Duration (Months)

Study Details

Study Description

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 French virtual patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerotic Cardiovascular Disease	Drug: Inclisiran sodium Drug: Placebo Drug: Ezetimibe Drug: Evolocumab

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 French 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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

54724 participants

Observational Model:

Other

Time Perspective:

Other

Official Title:

In Silico Non Interventional Secondary Use of Data Study Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in French Patients With Established Cardiovascular Disease

Anticipated Study Start Date :

Jul 30, 2023

Anticipated Primary Completion Date :

Oct 16, 2023

Anticipated Study Completion Date :

Oct 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Virtual Patient with ASCVD Virtual Patient with ASCVD and LDL-C ≥ 70 mg/dL despite receiving a well-tolerated high-intensity statin with or without ezetimibe. Each virtual patient is his own control.	Drug: Inclisiran sodium Drug: Inclisiran sodium 300 mg virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation. Drug: Placebo Drug: Placebo virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation. Drug: Ezetimibe Drug: Ezetimibe 10 mg virtually orally once a day until end of simulation. Drug: Evolocumab Drug: Evolocumab 140 mg virtually subcutaneously administered every two weeks until end of simulation.

Arm

Intervention/Treatment

Virtual Patient with ASCVD

Virtual Patient with ASCVD and LDL-C ≥ 70 mg/dL despite receiving a well-tolerated high-intensity statin with or without ezetimibe. Each virtual patient is his own control.

Drug: Inclisiran sodium

Drug: Inclisiran sodium 300 mg virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.

Drug: Placebo

Drug: Placebo virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.

Drug: Ezetimibe

Drug: Ezetimibe 10 mg virtually orally once a day until end of simulation.

Drug: Evolocumab

Drug: Evolocumab 140 mg virtually subcutaneously administered every two weeks until end of simulation.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria :

Patients with atherosclerotic CV disease, defined as any of the following

Previous MI

Previous ischemic stroke
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

Fasting LDL-C ≥ 70 mg/dL
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