Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
Condition: Homozygous Familial Hypercholesterolemia
MeSH terms: Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Hypercholesterolemia
Intervention: evinacumab; Placebo
Intervention description: IV administration of evinacumab; IV administration of placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 65.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: HoFH

Summary:

      The primary objective of the study is to demonstrate the reduction of low-density lipoprotein
      cholesterol (LDL-C) by evinacumab intravenously (IV) in comparison to placebo after 24 weeks
      in patients with homozygous familial hypercholesterolemia (HoFH). The secondary objectives of
      the study are to evaluate the effect of evinacumab IV on other lipid parameters, evaluate the
      effect of evinacumab on LDL-C goal attainment, assess the effect of evinacumab on eligibility
      for apheresis (using German and US apheresis criteria), evaluate the safety and tolerability
      of evinacumab in patients with HoFH, assess the pharmacokinetics (PK) of evinacumab in
      patients with HoFH and evaluate the potential development of anti-evinacumab antibodies.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Diagnosis of functional HoFH

          2. If undergoing LDL apheresis, must have initiated LDL apheresis at least 3 months prior
             to screening and must have been on a stable weekly or every other week schedule and/or
             stable settings for at least 8 weeks

          3. Willing to consistently maintain his/her usual low fat or heart-healthy diet for the
             duration of the study

        Key Exclusion Criteria:

          1. LDL-C level <70 mg/dL (1.81 mmol/L) at the screening visit

          2. Background medical Lipid Modifying Therapy (LMT) (if applicable) that has not been
             stable before the screening visit

          3. Lipid-apheresis schedule /apheresis settings (if applicable) that have not been stable
             for at least 8 weeks before the screening visit

          4. Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a
             dose/amount that has not been stable for at least 4 weeks prior to the screening visit

          5. Presence of any clinically significant uncontrolled endocrine disease known to
             influence serum lipids or lipoproteins

          6. Newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or
             poorly controlled (HbA1c >9%) diabetes

          7. History of a MI, unstable angina leading to hospitalization, coronary artery bypass
             graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia,
             carotid surgery or stenting, stroke, transient ischemic attack, valve replacement
             surgery, carotid revascularization, endovascular procedure or surgical intervention
             for peripheral vascular disease within 3 months prior to the screening visit

          8. Pregnant or breastfeeding women

          9. Sexually active women of child bearing potential (WOCBP), who are unwilling to
             practice a highly effective birth control method prior to the initial dose, during the
             study, and for 24 weeks after the last dose of study drug

         10. Men who are sexually active with women of child bearing potential (WOCBP) and are
             unwilling to consistently use condoms during the study drug treatment period and for
             24 weeks after the last dose of study drug regardless of vasectomy status

        Note: Other protocol defined inclusion/exclusion criteria may apply.