VictORION-INCLUSION is a Multicenter, Randomized, Open Label, Study of Inclisiran + Usual Care vs Usual Care Alone in an Inclusive and Underrepresented Population at High Risk for or Diagnosed With ASCVD Within a Pragmatic EHR Framework. (V-INCLUSION)

• ClinicalTrials.gov Identifier: NCT06249165
• Recruitment Status: Not yet recruiting
• First Posted: February 8, 2024
• Last Update Posted: May 9, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The purpose of this study is to measure the effectiveness of inclisiran compared to usual care in an inclusive study population (women, racial/ethnic minorities, and rural dwelling participants) which has historically been more likely to receive suboptimal lipid management, as a potential solution to improve care gaps. The study duration will be up to 360 days for participants randomized to the inclisiran with usual care arm and up to 720 days for participants initially randomized to the usual care arm.

Condition or disease	Intervention/treatment	Phase
Atherosclerotic Cardiovascular Disease	Drug: Inclisiran	Phase 4

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.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1440 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: randomized, controlled, multicenter, open-label two arm trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: July 24, 2024
• Estimated Primary Completion Date: June 8, 2026
• Estimated Study Completion Date: November 3, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of participants achieving LDL-C targets [ Time Frame: Day 360 ]

   Participants are considered to achieve LDL-C targets when:

   • Serum LDL-C < 70 mg/dL for ASCVD participants or
   • Serum LDL-C < 100 mg/dL for ASCVD risk equivalent participants

   Atherosclerotic Cardiovascular Disease (ASCVD) participants are those suffering from coronary artery disease (CAD), cerebrovascular disease (CeVD) or peripheral arterial disease (PAD).

   ASCVD risk equivalent participants are those suffering from Type 2 Diabetes Mellitus (DM), Heterozygous Familial Hypercholesterolemia (HeFH), or 10 year ASCVD event risk score ≥ 20% based on ACC/AHA pooled cohort cardiovascular risk equation/Framingham risk score or similar calculators.

Secondary Outcome Measures :

1. Number of participants achieving LDL-C targets by underrepresented and historically understudied populations [ Time Frame: Day 360 ]

   Achievement of LDL-C targets at Day 360 in underrepresented and historically understudied populations with disparate outcomes in LDL-C management in: Female participants, Black/African American participants, Hispanic/Latino participants and Rural participants

   Participants are considered to achieve LDL-C targets when:

   • Serum LDL-C < 70 mg/dL for ASCVD participants or
   • Serum LDL-C < 100 mg/dL for ASCVD risk equivalent participants
2. Absolute change from baseline in LDL-C [ Time Frame: Baseline, Day 360 ]
   Absolute change from baseline in LDL-C will be calculated to evaluate the effect of inclisiran + usual care compared to usual care alone on the change in LDL-C over time in the entire study population, ASCVD participants and ASCVD risk equivalent participants.
3. Percent change from baseline in LDL-C [ Time Frame: Baseline, Day 360 ]
   Percent change from baseline in LDL-C will be calculated to evaluate the effect of inclisiran + usual care compared to usual care alone on the change in LDL-C over time in the entire study population, ASCVD participants and ASCVD risk equivalent participants.
4. Average absolute change from baseline in LDL-C at each post-baseline visit [ Time Frame: Baseline, Day 360 ]
   Average absolute change from baseline in LDL-C at each post-baseline visit will be calculated to evaluate the effect of inclisiran + usual care compared to usual care alone on the change in LDL-C over time in the entire study population, ASCVD participants and ASCVD risk equivalent participants.
5. Average percent change from baseline in LDL-C at each post-baseline visit [ Time Frame: Baseline, Day 360 ]
   Average percent change from baseline in LDL-C at each post-baseline visit will be calculated to evaluate the effect of inclisiran + usual care compared to usual care alone on the change in LDL-C over time in the entire study population, ASCVD participants and ASCVD risk equivalent participants.
6. Number of ASCVD participants and ASCVD risk equivalent participants achieving LDL-C targets [ Time Frame: Day 360 ]

   Participants are considered to achieve LDL-C targets when:

   • Serum LDL-C < 70 mg/dL for ASCVD participants or
   • Serum LDL-C < 100 mg/dL for ASCVD risk equivalent participants

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

1. Males and females ≥18 years of age.

2. Patients must have clinical ASCVD or ASCVD risk equivalent diagnosis captured in EHR.

   ASCVD Risk Equivalent defined as:

   • History of Type 2 Diabetes Mellitus
   • 10 year ASCVD risk score ≥ 20% (based on ACC/AHA Pooled Cohort Equation ASCVD Risk Estimator (https://tools.acc.org/ldl/ascvd_risk_estimator/index.html#!/calulate/estimator/ )
   • History of heterozygous familial hyperlipidemia (HeFH) defined clinically (untreated LDL-C ≥ 190 mg/dL), by genetic testing, Dutch Lipid Network, or Simon Broome Criteria
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. Participants must be willing and able to give informed consent before initiation of any study related procedures and willing to comply with all required study procedures.
5. Participants are required to be on statin therapy, or have documented statin intolerance, as determined by the treating physician. Statin intolerant patients are eligible if the patient is so determined by the practitioner.

6. Participants to be chosen from historically underrepresented populations in cardiovascular clinical research and practice, including but not limited to female sex, Hispanic/Latino, Black/African-American, Asian, and Native Americans, as well as rural dwelling participants.

   -

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this study.

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. Pregnant or nursing (lactating) women.

4. 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 investigational drug. Basic contraception methods include:

   • Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
   • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
   • Male sterilization (at least 6 m prior to pre-screening). For female participants in the study, the vasectomized male partner should be the sole partner for that participant
   • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps)
   • Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking investigational drug.

   Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential.

5. New York Heart Association (NYHA) class III or IV heart failure or last known left ventricular ejection fraction <25%.
6. 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.
7. Uncontrolled hypertension: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite antihypertensive therapy.
8. 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 patients with Gilbert's syndrome) at pre-screening confirmed by a repeat measurement at least one week apart.
9. End-stage renal disease (ESRD)

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; +41613241111; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT06249165
• Other Study ID Numbers: CKJX839A1US10
• First Posted: February 8, 2024
• Last Update Posted: May 9, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Hyperlipidemia; Secondary Cardiovascular Prevention; Primary Prevention; Atherosclerotic Cardiovascular Disease (ASCVD); Hypercholesterolemia; Lipid lowering therapies; Inclisiran

Additional relevant MeSH terms:

Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases