VictORION-INCLUSION: Evaluating Inclisiran for Cholesterol Managment in Heart Disease (V-INCLUSION)

VictORION-INCLUSION: Evaluating INClisiran as a soLUtion to Improve LDL-C Management and cloSe Care Gaps in an Inclusive ASCVD and ASCVD Risk Equivalent populatiON

VictORION-INCLUSION (V-INCLUSION) seeks to evaluate the effectiveness of inclisiran as an innovative therapy with the potential to help bridge care gaps in historically understudied and undertreated populations by leveraging electronic health records (EHR) in multiple US Healthcare Systems (HCS) to systematically identify those at high risk for and already diagnosed with ASCVD for more expeditious achievement of LDL-C targets.

Study Overview

• Status: Active, not recruiting
• Conditions: Atherosclerotic Cardiovascular Disease
• Intervention / Treatment: Drug: Inclisiran

Detailed Description

The trial consists of two parts. Part 1 is a randomized, controlled, multicenter, open-label two arm trial comparing inclisiran and usual care versus usual care alone in an inclusive study population identified by electronic health records. Part 2 is a single arm trial consisting of Part 1 usual care participants initiating inclisiran at Day 360, and receiving two additional doses on day 450 and 630 (dosed in similar fashion to inclisiran + UC arm in Part 1). Approximately 1440 participants will be randomized to either inclisiran + usual care or to usual care only. Eligible participants must be at high risk for or be diagnosed with established ASCVD (prior CAD, PAD, CeVD event) and LDL-C above treatment threshold despite treatment with statin therapy (or with documented statin intolerance).

The study funder made a business decision to close the study to enrollment. Any patients identified and confirmed eligible prior to May 30, 2025 were permitted to be randomized through June 6, 2025. A total of 130 participants were enrolled. Participants randomized to Inclisiran + Usual Care will complete the study as originally planned. Participants randomized to Usual Care alone will have the option to receive inclisiran earlier if they choose to do so. They may also opt to complete only the Usual Care portion of the study (i.e., never receive study inclisiran) or to withdraw from the study. Usual Care participants will be required to sign an addendum to consent to these changes and identify their selection.

The study population will consist of underrepresented and historically understudied male and female participants (targeting 50% female, 70% underrepresented [Black/African American, Hispanic/Latino, Asian, other] and 10% rural participants of any sex or race/ethnicity) ≥18 years of age with a history of ASCVD (coronary artery disease, ischemic cerebrovascular disease or peripheral arterial disease) or ASCVD risk equivalent (HeFH, Type 2 DM, or 10 year ASCVD risk score ≥ 20%) who have elevated LDL-C (≥ 70 mg/dL or LDL-C ≥ 100 mg/dL) respectively) despite being treated with statin therapy. A total of approximately 1440 participants will be randomized to inclisiran + usual care or usual care in a 1:1 ratio at up to 30 US healthcare systems.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Univ. of Alabama - Birmingham
  • California
    • Orange, California, United States, 92868
      • Univ. of California - Irvine
    • San Francisco, California, United States, 94110
      • San Francisco General Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30324
      • Emory University
    • Hiram, Georgia, United States, 30141
      • Wellstar Paulding
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • JHU - Suburban Hospital
    • Columbia, Maryland, United States, 21044
      • Johns Hopkins
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Health
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska
  • New Jersey
    • Haddon Heights, New Jersey, United States, 08035
      • Heart House of NJ
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical Univ. of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist
    • Waco, Texas, United States, 76708
      • Baylor Scott & White - Waco
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Must meet all criteria below.

1. Males and females >= 18 years of age
2. Have clinical ASCVD or ASCVD risk equivalent diagnosis captured in EHR
3. Serum LDL-C ≥ 70 mg/dL for participants with ASCVD, or LDL-C ≥ 100 mg/dL for ASCVD risk equivalent participants, based on last recorded LDL-C value within the preceding eighteen (18) months without a subsequent change in lipid lowering therapy.
4. Willing and able to give informed consent before initiation of any study related procedures and willing to comply with all required study procedures.
5. On statin therapy, or have documented statin intolerance, as determined by the treating clinician. Participants for whom statin therapy has been recently initiated must be on stable therapy for at least 4 weeks and subsequent LDL-C must be above the threshold.
6. From historically underrepresented populations in cardiovascular clinical research, including at least one of the following: female sex; Hispanic/Latino ethnicity; Black/African-American, Asian, or Native American race; rural dwelling based on the HRSA definition for determining rural grant eligibility using the Federal Office of Rural Health Policy (FORHP) 2010 County and Census Tract file.

Exclusion Criteria: Cannot meet any criteria below.

1. Planned use of other investigational products or devices during the course of the study.
2. Treatment with monoclonal antibodies directed towards PCSK9 within 90 days or with inclisiran within 180 days of pre-screening.
3. History of hypersensitivity to the study treatment or its excipients or to other siRNA drugs.
4. Pregnant or nursing (lactating) women.
5. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment.
6. New York Heart Association (NYHA) class III or IV heart failure or last known left ventricular ejection fraction <25%.
7. Significant cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or other methods (i.e. via ablation etc.) at the time of pre-screening. Controlled arrhythmia is not an exclusion.
8. Uncontrolled hypertension: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite antihypertensive therapy.
9. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or alanine aminotransferase (ALT) elevation >3x ULN, aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation >2x ULN (except participants with Gilbert's syndrome) at pre-screening confirmed by a repeat measurement at least one week apart. Lack of repeat measurement is not considered an exclusion.
10. End-stage renal disease (ESRD), defined as being on dialysis of any kind.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual Care
Experimental: Inclisiran; Inclisiran + Usual Care	Drug: Inclisiran; Inclisiran sodium 300 mg/1.5 ml (equivalent to 284 mg inclisiran liquid) in prefilled syringe (PFS).; Other Names: Leqvio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of LDL-C targets	Achieving LDL-C targets (LDL-C < 70 mg/dL for ASCVD participants or LDL-C < 100 for ASCVD risk equivalent participants) (yes/no)	Day 360

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of LDL-C targets by subgroup	Achieving LDL-C targets at Day 360 in the following participant subgroups: Female, Black/African American, Hispanic/Latino, Rural.	Day 360
Change in LDL-C from baseline by population	Change in LDL-C value from baseline (absolute change, percent change, average absolute change, average percent change) in entire population, ASCVD population, and ASCVD risk equivalent population	Day 360
Achievement of LDL-C targets by population	Achieving LDL-C target at day 360 in ASCVD population and ASCVD risk equivalent population	Day 360
Safety and tolerability of inclisiran	Incidence of AEs and SAEs	Through study completion, up to approximately 630 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Treatment Satisfaction Questionnaire for Medication Score	Change in Treatment Satisfaction Questionnaire for Medication (TSQM) from baseline. Higher score indicates greater satisfaction with treatment.	Day 360, Day 720
Change in Medication Adherence Report Scale	Change in Medication Adherence Report Scale (MARS-5) from baseline. Higher score indicates greater adherence to medication regimen.	Day 360, Day 720

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Neha Pagidipati, MD, Duke Clinical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: January 31, 2024
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Estimated): November 6, 2025
• Last Update Submitted That Met QC Criteria: November 4, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Hypercholesterolemia; Hyperlipidemia; Inclisiran; Primary Prevention; Secondary Cardiovascular Prevention; Atherosclerotic Cardiovascular Disease (ASCVD); Lipid lowering therapies
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Metabolic Diseases; Dyslipidemias; Lipid Metabolism Disorders; Arteriosclerosis; Arterial Occlusive Diseases; Nutritional and Metabolic Diseases; Hypercholesterolemia; Atherosclerosis; Hyperlipidemias; ALN-PCS
• Other Study ID Numbers: Pro00115658; CKJX839A1US10 (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes