Clinical trial NCT06249165: VictORION-INCLUSION: Evaluating Inclisiran for Cholesterol Managment in Heart Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Atherosclerotic Cardiovascular Disease
Keywords: Hyperlipidemia
Secondary Cardiovascular Prevention
Primary Prevention
Atherosclerotic Cardiovascular Disease (ASCVD)
Hypercholesterolemia
Lipid lowering therapies
Inclisiran
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2024-02-08
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, controlled, multicenter, open-label two arm trial
Primary purpose: TREATMENT

Brief summary: 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.

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 population will consist of underrepresented and historically understudied male and female participants (at least 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 approximately 30 US healthcare systems.

Eligibility criteria: 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.
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.

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.
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.
10. End-stage renal disease (ESRD)

Primary outcomes:
measure: Achievement of LDL-C targets
timeFrame: Day 360
Secondary outcomes:
measure: Number of participants achieving LDL-C targets by subgroups
timeFrame: Day 360
measure: Absolute change from baseline in LDL-C
timeFrame: Day 360
measure: Percent change from baseline in LDL-C
timeFrame: Day 360
measure: Average absolute change from baseline in LDL-C at each post-baseline visit
timeFrame: Day 90, Day 270, Day 360
measure: Average percent change from baseline in LDL-C at each post-baseline visit
timeFrame: Day 90, Day 270, Day 360
Other outcomes:
measure: Change in Treatment Satisfaction Questionnaire for Medication Score
timeFrame: Day 360, Day 720
measure: Change in Medication Adherence Report Scale
timeFrame: Day 360, Day 720
Locations:
city: Birmingham
country: United States
facility: Univ. of Alabama - Birmingham
state: Alabama
city: Orange
country: United States
facility: Univ. of California - Irvine
state: California
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Hiram
country: United States
facility: Wellstar Paulding
state: Georgia
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Bethesda
country: United States
facility: JHU - Suburban Hospital
state: Maryland
city: Columbia
country: United States
facility: Johns Hopkins
state: Maryland
city: Duluth
country: United States
facility: Essentia Health
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Haddon Heights
country: United States
facility: Heart House of NJ
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical Univ. of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Waco
country: United States
facility: Baylor Scott & White - Waco
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Duke Clinical Research Institute
name: Neha Pagidipati, MD
role: PRINCIPAL_INVESTIGATOR
References: