Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia
Condition: Homozygous Familial Hypercholesterolemia
MeSH terms: Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Hypercholesterolemia
Intervention: Evinacumab
Intervention description: Part A: Single IV dose Part B & C: IV dose Q4W
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 5 Years
Maximum age: 11 Years
Healthy volunteers: No
Keywords: HoFH

Summary:

      The primary objective for Part A of the study is to assess the pharmacokinetics (PK) of
      evinacumab in pediatric patients with homozygous familial hypercholesterolemia (HoFH).

      The primary objective for Part B of the study is to demonstrate a reduction of low-density
      lipoprotein cholesterol (LDL-C) by evinacumab in pediatric (5 to 11 years of age) patients
      with HoFH.

      The secondary objective for Part A of the study is to evaluate the safety and tolerability of
      evinacumab administered intravenous (IV) in pediatric patients with HoFH.

      The secondary objectives for Part B of the study are:

        -  To evaluate the effect of evinacumab on other lipid parameters (ie, apolipoprotein B
           (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC),
           lipoprotein a [Lp(a)]) in pediatric patients with HoFH

        -  To evaluate the safety and tolerability of evinacumab administered IV in pediatric
           patients with HoFH

        -  To assess the PK of evinacumab in pediatric patients with HoFH

        -  To assess the immunogenicity of evinacumab in pediatric patients with HoFH over time

        -  To evaluate patient efficacy by mutation status
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Diagnosis of functional HoFH by either genetic or clinical criteria as defined in the
             protocol

          2. LDL-C >130 mg/dL at the screening visit

          3. Body weight ≥15 kg

          4. Receiving stable maximally tolerated therapy*at the screening visit *Maximally
             tolerated therapy could include a daily statin.

          5. Willing and able to comply with clinic visits and study-related procedures

          6. Parent(s) or legal guardian(s) must provide the signed informed consent form (ICF).
             Patients ≥5 years of age (or above age determined by the IRB/EC and in accordance with
             the local regulations and requirements) must also provide informed assent forms (IAFs)
             to enroll in the study, and sign and date a separate IAF or ICF signed by the
             parent(s)/legal guardian(s) (as appropriate based on local regulations and
             requirements)

        Key Exclusion Criteria:

          1. Background pharmacologic LMT, nutraceuticals or over-the-counter (OTC) therapies known
             to affect lipids, at a dose/regimen that has not been stable for at least 4 weeks (8
             weeks for PCSK9 inhibitors) before the screening visit and patient is unwilling to
             enter the run-in period

          2. For patients entering Part A, unable to temporarily discontinue apheresis from the
             baseline visit through the week 4 visit

          3. Receiving lipid apheresis, a setting (if applicable) and schedule that has not been
             stable for approximately 8 weeks before the screening visit or an apheresis schedule
             that is not anticipated to be stable over the duration of the treatment period (48
             weeks).

          4. Plasmapheresis within 8 weeks of the screening visit, or plans to undergo
             plasmapheresis during Part A or Part B

          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 diabetes as defined in the protocol

        Note: Other protocol-defined criteria apply