Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol
Condition: ASCVD; Risk Factor, Cardiovascular; Elevated Cholesterol
MeSH terms: Hypercholesterolemia
Intervention: Inclisiran Sodium; Placebo
Intervention description: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.; Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 1617.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Inclisiran sodium; ASCVD; LDL-C

Summary:

      This is a Phase III, placebo-controlled, double-blind, randomized study in participants with
      ASCVD or ASCVD-Risk equivalents and elevated LDL-C despite maximum tolerated dose of LDL-C
      lowering therapies to evaluate the efficacy, safety, and tolerability of subcutaneous (SC)
      inclisiran injection(s). The study will be an international multicenter study (non-United
      States).
    

Eligibility criteria:

        Inclusion Criteria:

        Participants may be included if they meet all of the following inclusion criteria prior to
        randomization:

          1. Male or female participants ≥18 years of age.

          2. History of ASCVD (coronary heart disease [CHD], cardiovascular disease [CVD], or
             peripheral arterial disease [PAD]).

          3. Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL).

          4. Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.

          5. Calculated glomerular filtration rate >30 mL/min by estimated glomerular filtration
             rate (eGFR) using standardized clinical methodology

          6. Participants on statins should be receiving a maximally tolerated dose.

          7. Participants not receiving statins must have documented evidence of intolerance to all
             doses of at least 2 different statins.

          8. Subjects on lipid-lower therapies (such as a statin and/or ezetimibe) should be on a
             stable dose for ≥30 days before screening with no planned medication or dose change
             during study participation.

          9. Subjects were willing and able to give informed consent before initiation of any
             study-related procedures and willing to comply with all required study procedures

        Exclusion Criteria:

        Participants will be excluded from the study if any of the following exclusion criteria
        apply prior to randomization:

          1. New York Heart Association (NYHA) class IV heart failure.

          2. Uncontrolled cardiac arrhythmia.

          3. Uncontrolled severe hypertension.

          4. Active liver disease.

          5. Females who are pregnant or nursing, or who are of childbearing potential and
             unwilling to use at least 2 methods of highly effective contraception (failure rate
             less than 1% per year) (for example, combined oral contraceptives, barrier methods,
             approved contraceptive implant, long-term injectable contraception, or intrauterine
             device) for the entire duration of the study. Exemptions from this criterion:

               1. Women >2 years postmenopausal (defined as 1 year or longer since last menstrual
                  period) and more than 55 years of age.

               2. Postmenopausal women (as defined above) and less than 55 years of age with a
                  negative pregnancy test within 24 hours of randomization.

               3. Women who are surgically sterilized at least 3 months prior to enrollment.

          6. Males who are unwilling to use an acceptable method of birth control during the entire
             study period (such as condom with spermicide).

          7. Treatment with other investigational products or devices within 30 days or 5
             half-lives of the screening visit, whichever is longer.

          8. Treatment (within 90 days of screening) with monoclonal antibodies directed towards
             PCSK9.

        The above information is not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.