Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH)
Condition: Heterozygous Familial Hypercholesterolemia; Elevated Cholesterol
MeSH terms: Hyperlipoproteinemia Type II; Hypercholesterolemia
Intervention: Inclisiran; 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: 482.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HeFH; LDL-C; Inclisiran

Summary:

      This is a Phase III, placebo-controlled, double-blind, randomized study in participants with
      HeFH and elevated LDL-C to evaluate the efficacy, safety, and tolerability of subcutaneous
      (SC) injection(s) of inclisiran. The study will be multicenter and international.
    

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 HeFH with a diagnosis of HeFH by genetic testing; and/or a documented
             history of untreated LDL-C of >190 mg/dL, and a family history of familial
             hypercholesterolemia, elevated cholesterol or early heart disease that may indicate
             familial hypercholesterolemia.

          3. Serum LDL-C ≥2.6 millimoles (mmol)/liter (L) (≥100 mg/dL) at screening.

          4. Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.

          5. Participants on statins should be receiving a maximally tolerated dose.

          6. Participants not receiving statins must have documented evidence of intolerance to all
             doses of at least 2 different statins.

          7. Participants on lipid-lowering 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.

        Exclusion Criteria:

        Participants will be excluded from the study if any of the following exclusion criteria
        apply immediately 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) (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 (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.