Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia

Summary: The primary objective of the study is to evaluate the reduction of low-density lipoprotein cholesterol (LDL-C) by evinacumab in comparison to placebo after 16 weeks in patients with primary hypercholesterolemia (heterozygous familial hypercholesterolemia [HeFH], or non-HeFH with a history of clinical atherosclerotic cardiovascular disease [clinical ASCVD]) with LDL-C ≥ 100 mg/dL (2.59 mmol/L) despite maximally tolerated statin and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy.


Eligibility: The inclusion/ exclusion criteria below, include, but are not limited to, the following:
  Key Inclusion Criteria:
  1. Men and women, ages 18 through 75 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. 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
  6. Serum LDL-C ≥ 100 mg/dL at screening (1 repeat lab is allowed)
  7. 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 II-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. Sexually active men unwilling to use acceptable birth control.

Relevance to patient case: not relevant