A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.

• ClinicalTrials.gov Identifier: NCT05739383
• Recruitment Status: Recruiting
• First Posted: February 22, 2023
• Last Update Posted: April 24, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: February 13, 2023
• First Posted Date: February 22, 2023
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: March 9, 2023
• Estimated Primary Completion Date: April 16, 2029 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 13, 2023)

Time to the first occurrence of 4P-MACE [ Time Frame: Time to the first occurrence of 4P-MACE (up to approximately 75 months) ]

4-Point-Major Adverse Cardiovascular Events (4P-MACE): composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent coronary revascularization.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 13, 2023)

• Time to the first occurrence of 3P-MACE [ Time Frame: Time to the first occurrence of 3P-MACE (up to approximately 75 months) ]
  3-Point-Major Adverse Cardiovascular Events (3P-MACE): composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke)
• Total number of first or repeated CV events (4P MACE) [ Time Frame: up to 75 months ]
  Total 4P-MACE (composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent coronary revascularization)
• Total number of first or repeated CV events (3P MACE) [ Time Frame: up to 75 months ]
  Total 3P-MACE (composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke)
• Time to occurrence of Cardiovascular death [ Time Frame: Time to Cardiovascular death (up to 75 months) ]
  CV death is defined as death due to cardiovascular events.
• Time to occurrence of death due to any reason [ Time Frame: Time to all-cause mortality (up to 75 months) ]
  All-cause mortality is death due to any reason.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
• Official Title: A Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Effect of Inclisiran on Preventing Major Adverse Cardiovascular Events in High-risk Primary Prevention Patients (VICTORION-1 PREVENT)
• Brief Summary: CKJX839D12302 is a pivotal Phase III study designed to test the hypothesis that treatment with inclisiran sodium 300 milligram (mg) subcutaneous (s.c.) administered on Day 1, Day 90, and every 6 months thereafter in patients at high cardiovascular (CV) risk without a prior major atherosclerotic cardiovascular disease (ASCVD) event will significantly reduce the risk of 4-Point-Major Adverse Cardiovascular Events (4P-MACE) defined as a composite of CV death, non-fatal myocardial infarction (MI), non-fatal ischemic stroke, and urgent coronary revascularization, compared to placebo.

Detailed Description

The purpose of this study is to evaluate inclisiran sodium 300 mg s.c. (equivalent to 284 mg inclisiran) compared to placebo on reducing the risk of 4P-MACE in adult patients at high risk for their first major adverse cardiovascular event.

Randomized participants will receive study medication (inclisiran or placebo), administered s.c. on Day 1, Day 90, then every 6 months thereafter. This is an event-driven study. Therefore, the study will continue until the required number of clinical events have occurred across both treatment arms, and all participants have a minimum of 3 years of follow-up during the double-blind treatment period.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Primary Prevention of Atherosclerotic Cardiovascular Disease

Intervention

• Drug: Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL
  Subcutaneous injection in pre-filled syringe.
  Other Name: KJX839
• Drug: Placebo in 1.5ml
  Matching placebo in 1.5ml solution for injection

Study Arms

• Experimental: Inclisiran sodium 300mg

  Inclisiran sodium 300 mg in 1.5 mL solution for injection (subcutaneous) in pre-filled syringe.

  Randomized in a 1:1 ratio with matching placebo

  Intervention: Drug: Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL
• Placebo Comparator: Placebo
  Matching placebo in 1.5ml pre-filled syringe. Randomized in a 1:1 ratio with Inclisiran.
  Intervention: Drug: Placebo in 1.5ml

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 13, 2023): 14000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 16, 2029
• Estimated Primary Completion Date: April 16, 2029 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• At an increased risk for a first MACE (i.e., no prior major ASCVD event), defined as any one of the following:

  1. Evidence of atherosclerotic coronary artery disease (CAD) on computer tomography (CT) or invasive coronary angiogram defined as a coronary artery stenosis ≥20% but <50% in the left main coronary artery or stenosis ≥20% but <70% in any other major epicardial coronary artery, or
  2. Coronary artery calcium (CAC) score obtained by CT-scan ≥100 Agatston units, or
  3. High 10-year ASCVD risk ≥20%, or
  4. Intermediate 10-year ASCVD risk 7.5% - <20% with at least 2 risk-enhancing factors.
• LDL-C ≥70 mg/dL (≥1.81 mmol/L) but <190 mg/dL (<4.91 mmol/L) at the screening visit. If on a background lipid lowering therapy, the dose should be stable for at least 4 weeks prior to the screening visit and the participant should be willing to remain on this background therapy for the entire duration of the study.

Exclusion Criteria:

• History of major ASCVD event.
• History of, or planned, ischemia-driven revascularization in a coronary or extracoronary arterial bed prior to randomization
• Absence of coronary atherosclerosis on a CT angiogram or an invasive coronary angiogram in the 2 years prior to randomization
• Coronary artery calcium (CAC) score of 0 obtained in the 2 years prior to randomization
• Active liver disease or hepatic dysfunction
• Previous, current, or planned treatment with a monoclonal antibody (mAb) directed toward proprotein convertase subtilisin/kexin type 9 (PCSK9) (e.g., evolocumab, alirocumab)
• Pregnant or nursing (lactating) women
• Women of childbearing potential unless they are using effective methods of contraception while taking study treatment which includes for 6 months after last study drug administration

Other protocol-defined inclusion/exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 79 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Croatia, Czechia, Denmark, Estonia, France, Greece, Hong Kong, Hungary, India, Israel, Italy, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Philippines, Poland, Portugal, Romania, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05739383
• Other Study ID Numbers: CKJX839D12302
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: April 2024