Study of Inclisiran to Prevent Cardiovascular (CV) Events in Participants With Established Cardiovascular Disease (VICTORION-2P)

• ClinicalTrials.gov Identifier: NCT05030428
• Recruitment Status: Active, not recruiting
• First Posted: September 1, 2021
• Last Update Posted: March 1, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: August 17, 2021
• First Posted Date: September 1, 2021
• Last Update Posted Date: March 1, 2024
• Actual Study Start Date: November 23, 2021
• Estimated Primary Completion Date: October 13, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 25, 2021)

Time to First Occurrence of 3P-MACE (3-Point Major Adverse Cardiovascular Events) [ Time Frame: From randomization to total follow-up time (up to 72 months) ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 2, 2023)

• Time to Occurrence of Cardiovascular (CV) Death [ Time Frame: From randomization to total follow-up time (up to 72 months) ]
  CV death is defined as death due to cardiovascular events
• Time to First Occurrence of 4P-MACE (4-Point Major Adverse Cardiovascular Events) [ Time Frame: From randomization to total follow-up time (up to 72 months) ]
  A composite 4P- MACE is defined as CV death, non-fatal MI, non-fatal ischemic stroke and urgent coronary revascularization.
• Time to first occurrence of Major Limb Adverse Events (MALE) [ Time Frame: From randomization to total follow-up time (up to 72 months) ]
  Major Limb Adverse Events including acute lower limb ischemia, lower limb amputation due to ischemia, or urgent lower limb revascularization for ischemia
• Time to occurrence of all-cause death [ Time Frame: From randomization to total follow-up time (up to 72 months) ]
  All-Cause death is defined as: all deaths from randomization until up to 72 months

Original Secondary Outcome Measures (submitted: August 25, 2021)

• Time to Occurrence of Cardiovascular (CV) Death [ Time Frame: From randomization to total follow-up time (up to 72 months) ]
  CV death is defined as death due to cardiovascular events
• Time to First Occurrence of 4P-MACE (4-Point Major Adverse Cardiovascular Events) [ Time Frame: From randomization to total follow-up time (up to 72 months) ]
  A composite 4P- MACE is defined as CV death, non-fatal MI, non-fatal ischemic stroke and urgent coronary revascularization.
• Time to occurrence of all-cause death [ Time Frame: From randomization to total follow-up time (up to 72 months) ]
  All-Cause death is defined as: all deaths from randomization until up to 72 months

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Inclisiran to Prevent Cardiovascular (CV) Events in Participants With Established Cardiovascular Disease
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multicenter Trial, Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in Participants With Established Cardiovascular Disease (VICTORION-2 PREVENT)
• Brief Summary: Study CKJX839B12302 is a pivotal Phase III trial to evaluate the benefits of inclisiran on major adverse cardiovascular (MACE) events in participants with established cardiovascular disease (CVD).
• Detailed Description: Purpose of this study is to test the hypothesis that treatment with inclisiran sodium 300 mg s.c. administered on Day 1, Month 3 (Day 90), and every 6 months thereafter taken in addition to well-tolerated high-intensity statin therapy in participants with established ASCVD will significantly reduce the risk of 3-Point-Major Adverse Cardiovascular Events (3P-MACE) defined as a composite of CV death, non-fatal myocardial infarction (MI) and non-fatal ischemic stroke. This will be compared to placebo in adjunct to well-tolerated high-intensity statin therapy.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

randomized, double-blind, parallel group, placebo-controlled, multi-center, event-driven study

Masking: Double (Participant, Investigator)
Masking Description:

Double-blind

Primary Purpose: Treatment

• Condition: Atherosclerotic Cardiovascular Disease

Intervention

• Drug: Inclisiran sodium 300 mg
  Subcutaneously injected on Day 1, Month 3 (Day 90) and every 6 months thereafter until EOS visit
• Drug: Placebo
  Subcutaneously injected on Day 1, Month 3 (Day 90) and every 6 months thereafter until EOS visit

Study Arms

• Experimental: Inclisiran sodium
  Subcutaneous injection
  Intervention: Drug: Inclisiran sodium 300 mg
• Placebo Comparator: Placebo
  Subcutaneous injection
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 29, 2024): 17013
• Original Estimated Enrollment (submitted: August 25, 2021): 15000
• Estimated Study Completion Date: October 13, 2027
• Estimated Primary Completion Date: October 13, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Fasting LDL-C ≥ 70 mg/dL at randomization visit
2. Stable (greater than or equal to 4 weeks) and well-tolerated lipid-lowering regimen (including e.g. with or without Ezetimibe) that must include a high-intensity statin therapy with either atorvastatin greater than or equal to 40 mg QD or rosuvastatin greater than or equal to 20 mg QD

3. Established CV disease defined as ANY of the following three conditions

   1. Spontaneous Myocardial infarction ≥ 4 weeks from screening visit
   2. History of ischemic stroke occurred ≥ 4 weeks prior to the Screening visit
   3. Symptomatic peripheral arterial disease (PAD) evidenced by either intermittent claudication with ankle brachial index (ABI) < 0.85, prior peripheral arterial revascularization procedure, or, amputation due to atherosclerotic disease.

Exclusion Criteria:

1. Acute coronary syndrome, stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease < 4 weeks before screening visit
2. Treatment with PCSK9 inhibitors (e.g. evolocumab, alirocumab) within 90 days or planned use post first study visit
3. Planned or expected cardiac, cerebrovascular or peripheral artery surgery or re-vascularization within the 6 months after the first study visit
4. Heart failure NYHA class III or IV
5. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver
6. Previous exposure to inclisiran or any other non-mAb PCSK9-targeted therapy, either as an investigational or marketed drug within 2 years
7. Severe concomitant non-CV disease that is expected to reduce life expectancy to less than 5 years
8. History of malignancy that required surgery radiation therapy and/or systemic therapy during the 3 years prior to the first study visit
9. Pregnant or nursing (lactating) women

Other protocol-defined inclusion/exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Estonia, Finland, France, Greece, Hungary, Iceland, India, Israel, Italy, Japan, Kenya, Korea, Republic of, Latvia, Lithuania, Malaysia, Mauritius, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United States

Administrative Information

• NCT Number: NCT05030428
• Other Study ID Numbers: CKJX839B12302
• 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: February 2024