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

Prior treatment

• Planned use of other investigational products or devices during the course of the study.
• Treatment with monoclonal antibodies directed towards PCSK9 within 90 days or with inclisiran within 180 days of pre-screening.
• 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.
• Uncontrolled hypertension: systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg prior to randomization despite antihypertensive therapy.

Other illness

• History of hypersensitivity to the study treatment or its excipients or to other siRNA drugs.
• End-stage renal disease (ESRD), defined as being on dialysis of any kind.

Lab values

• New York Heart Association (NYHA) class III or IV heart failure or last known left ventricular ejection fraction \<25%.
• 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.

Other

• Pregnant or nursing (lactating) women.
• 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.

• Males and females \>= 18 years of age
• Have clinical ASCVD or ASCVD risk equivalent diagnosis captured in EHR
• 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.
• Willing and able to give informed consent before initiation of any study related procedures and willing to comply with all required study procedures.
• 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.
• 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.