Study of Efficacy and Safety of Inclisiran in Japanese Participants With High Cardiovascular Risk and Elevated LDL-C
Condition: Hypercholesterolemia; Heterozygous Familial Hypercholesterolemia
MeSH terms: Hyperlipoproteinemia Type II; Hypercholesterolemia
Intervention: Inclisiran sodium; Placebo
Intervention description: Subcutaneously injected on Day 1, 90 and 270.; Subcutaneously injected on Day 1, 90, and 270.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 312.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: inclisiran; siRNA; dyslipidemia; PCSK9; Hypercholesterolemia; LDL-C

Summary:

      This was a placebo-controlled, double-blind, randomized trial in Japanese participants with
      history of coronary artery disease (CAD) or participants categorized in 'high risk' by JAS
      2017 guideline, or Japanese participants with heterozygous familial hypercholesterolemia
      (HeFH) and elevated Low-density lipoprotein cholesterol (LDL-C) despite maximum tolerated
      dose of statin(s) to evaluate the efficacy, safety, tolerability, and PK of subcutaneous
      inclisiran injection(s).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with history of CAD or participants categorized in 'high risk' by Japan
             Atherosclerosis Society (JAS) 2017 guidelines or participants with heterozygous
             familial hypercholesterolemia (HeFH)

          -  As per the JAS 2017 guideline, participants not meeting the LDL-C management targets.

          -  Participants on statins should be receiving a maximally tolerated dose.

          -  Participants not receiving statins must have documented evidence of intolerance to at
             least one statin.

          -  The lipid-lowering therapy should have remained stable for ≥ 30 days before screening
             with no planned medication/ dose change until Day 180

        Exclusion Criteria:

          -  Participants diagnosed with homozygous familial hypercholesterolemia (HoFH).

          -  Treatment (within 90 days of screening) with monoclonal antibodies directed towards
             PCSK9.

          -  New York Heart Association (NYHA) class IV heart failure or last known left
             ventricular ejection fraction <25%.

          -  Cardiac arrhythmia within 3 months prior to randomization that is not controlled by
             medication or via ablation.

          -  Uncontrolled hypertension: systolic blood pressure >160 mmHg or diastolic blood
             pressure >100 mmHg prior to randomization despite antihypertensive therapy.

          -  Active liver disease defined as any known current infectious, neoplastic, or metabolic
             pathology of the liver or unexplained elevations in alanine aminotransferase (ALT),
             aspartate aminotransferase (AST), >3x the upper limit of normal (ULN), or total
             bilirubin >2x ULN at screening.

          -  Severe concomitant non-cardiovascular disease that carries the risk of reducing life
             expectancy to less than 2 years.