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

NCT05974345 | Completed

• 1 other identifier: CKJX839B1FR01
• Study Type: observational
• Target: 204,691
• Locations: 1 country
• Sites: 1

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.

Conditions

Atherosclerotic Cardiovascular Disease

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

Outcome Measures

Primary Outcomes (2)

• 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)

  3P-MACE is a confirmed composite endpoint which includes cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke.

  5 years of follow-up

• Time to the first occurrence between trial start and end of follow-up of CV death

  CV death is defined as death due to cardiovascular events

  5 years of follow-up

Secondary Outcomes (5)

• Time to the first occurrence between trial start and end of follow-up of MI (non-fatal or fatal)

  5 years of follow-up

• 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

• 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.

• Time adjusted percentage change in LDL-C

  From baseline between Day 90 and the end of follow-up period (up to 5 years)

Study Arms (1)

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: Placebo; Drug: Ezetimibe; Drug: Evolocumab

Interventions

Inclisiran sodium DRUG

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

Virtual Patient with ASCVD

Placebo DRUG

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

Virtual Patient with ASCVD

Ezetimibe DRUG

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

Virtual Patient with ASCVD

Evolocumab DRUG

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

Virtual Patient with ASCVD

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Virtual Patient with ASCVD (previous MI, previous ischemic stroke, previous peripheral arterial disease) and LDL-C ≥ 70 mg/dL despite receiving a well-tolerated high-intensity statin with or without ezetimibe.

You may qualify if:

• 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
• Fasting LDL-C ≥ 70 mg/dL
• Under stable (≥ 4 weeks) well-tolerated high-intensity statin with or without ezetimibe.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Rueil-Malmaison, 92563, France

Location

Related Publications (1)

• Angoulvant D, Granjeon-Noriot S, Amarenco P, Bastien A, Bechet E, Boccara F, Boissel JP, Cariou B, Courcelles E, Diatchenko A, Filipovics A, Kahoul R, Mahe G, Peyronnet E, Portal L, Porte S, Wang Y, Steg PG. In-silico trial emulation to predict the cardiovascular protection of new lipid-lowering drugs: an illustration through the design of the SIRIUS programme. Eur J Prev Cardiol. 2024 Nov 11;31(15):1820-1830. doi: 10.1093/eurjpc/zwae254.

  PMID: 39101472 DERIVED

MeSH Terms

Conditions

Atherosclerosis; Hypercholesterolemia; Dyslipidemias; Hyperlipidemias; Myocardial Infarction; Ischemic Stroke; Peripheral Arterial Disease; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Interventions

Ezetimibe; evolocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Myocardial Ischemia; Heart Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2023
• First Posted: August 3, 2023
• Study Start: November 3, 2023
• Primary Completion: December 15, 2023
• Study Completion: December 15, 2023
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)