Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Intervention: Evinacumab; Matching placebo; Background Lipid Modifying Therapy (LMT)
Intervention description: SC or IV administration; SC or IV administration; All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 272.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The primary objective of the study is to evaluate the reduction of LDL-C by evinacumab in
      comparison to placebo after 16 weeks in patients with primary hypercholesterolemia (HeFH, or
      non-HeFH with a history of clinical ASCVD) with persistent hypercholesterolemia despite
      receiving maximally-tolerated LMT. Persistent hypercholesterolemia is defined as LDL-C ≥70
      mg/dL (1.81 mmol/L) for those patients with clinical ASCVD and LDL-C ≥100 mg/dL (2.59 mmol/L)
      for those patients without clinical ASCVD.
    

Eligibility criteria:

        The inclusion/ exclusion criteria below, include, but are not limited to, the following:

        Key Inclusion Criteria:

          1. Men and women, ages 18 through 80 at the screening visit

          2. Diagnosis of primary hypercholesterolemia, either HeFH or non-HeFH with clinical ASCVD

          3. A history of clinical ASCVD, for those patients who are non-HeFH.

          4. Receiving a stable maximally tolerated statin (± ezetimibe) for at least 4 weeks at
             screening

          5. For those patients with HeFH who are not receiving a statin at screening,
             documentation of inability to tolerate at least 2 statins.

          6. Receiving alirocumab 150 mg SC Q2W, OR evolocumab 140 mg SC Q2W or 420 mg SC Q4W for
             at least 8 weeks prior to the screening visit

          7. For those patients with a history of clinical ASCVD, serum LDL-C ≥ 70 mg/dL at
             screening (1 repeat lab is allowed)

          8. For those patients without a history of clinical ASCVD, serum LDL-C ≥ 100 mg/dL at
             screening (1 repeat lab is allowed)

          9. Provide signed informed consent

        Key Exclusion Criteria:

          1. Known history of homozygous FH (clinically, or by previous genotyping)

          2. Presence of any clinically significant uncontrolled endocrine disease known to
             influence serum lipids or lipoproteins

          3. Newly diagnosed diabetes (within 3 months prior to screening)

          4. Use of thyroid medications (except for replacement therapy which has been stable for
             at least 12 weeks before screening)

          5. Laboratory findings during screening period (not including randomization labs):

               1. Triglycerides > 400 mg/dL (> 4.52 mmol/L) for patients without a known history of
                  diabetes mellitus; OR Triglycerides > 300 mg/dL (> 3.39 mmol/L) for patients with
                  a known history of diabetes mellitus

               2. Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody
                  (associated with a positive HCV ribonucleic acid [RNA] polymerase chain reaction)

               3. Positive serum beta-human chorionic gonadotropin or urine pregnancy test in women
                  of childbearing potential

               4. Estimated glomerular filtration rate < 30 mL/min/1.73 m^2

               5. TSH > 1.5 x ULN

               6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x ULN

          6. Systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at screening
             visit or time of randomization

          7. History of heart failure (New York Heart Association [NYHA] Class III-IV) within 12
             months before screening

          8. History of MI, unstable angina leading to hospitalization, CABG surgery, PCI,
             uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, TIA, carotid
             revascularization, endovascular procedure or surgical intervention for peripheral
             vascular disease within 3 months prior screening

          9. History of cancer within the past 5 years (except for adequately treated basal cell
             skin cancer, squamous cell skin cancer, or in situ cervical cancer)

         10. Having received LDL apheresis within 2 months before screening

         11. Pregnant or breast-feeding women

         12. Women of childbearing potential who are unwilling to practice a highly effective birth
             control method

         13. Men who are sexually active with women of childbearing potential (WOCBP) and are
             unwilling to consistently use condoms during the study drug treatment period
             regardless of vasectomy status.