Pharmacodynamic Biomarkers to Support Biosimilar Development: PCSK9 Inhibitors
Condition: Healthy Subjects; Pharmacokinetics; Pharmacodynamics
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and
      alirocumab across an appropriate dose range to inform clinical trial operating
      characteristics for future clinical pharmacology pharmacodynamics similarity studies.

      This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy
      subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and
      high) of each drug (evolocumab and alirocumab ) or placebo.
    

Detailed description: 
      This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and
      alirocumab, two monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin
      type 9 (PCSK9), across an appropriate dose range to inform clinical trial operating
      characteristics for future clinical pharmacology pharmacodynamics similarity studies.

      This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy
      subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and
      high) of each drug (evolocumab or alirocumab) or placebo. Evolocumab doses are 21, 35, 70,
      and 140 mg. Reslizumab doses are 15, 25, 50, and 100 mg . Each arm will include 8 subjects (4
      male and 4 female).

      Subjects will be admitted for treatment on day -1 and receive a single dose of study drug or
      placebo on day 1. Depending on the treatment arm, subjects will remain in confinement for one
      week and continue follow-up through day 42, 56, or 84.

      Blood samples (approximately 5 mL per sample) will be collected for determination of plasma
      concentrations for study drug. Additional blood samples will be collected for lipid analysis
      and determination of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB)
      (5 mL per sample; pharmacodynamic measure) and exploratory proteomics analyses (5 mL per
      sample).

      Safety evaluations will include adverse event (AE) monitoring, vital sign measurements, and
      physical examinations. All AEs reported by the subject or observed by the investigator or
      clinical research unit (CRU) staff will be recorded. Any AE reported after the informed
      consent is signed and before study drug application will be recorded as medical history.
    

Intervention name(s): Evolocumab; Evolocumab; Evolocumab; Evolocumab; Alirocumab; Alirocumab; Alirocumab; Alirocumab; Placebo
Intervention type(s): Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological
Intervention description(s): Evolocumab 21 mg administered SC; Evolocumab 35 mg administered SC; Evolocumab 70 mg administered SC; Evolocumab 140 mg administered SC; Alirocumab 15 mg administered SC; Alirocumab 25 mg administered SC; Alirocumab 50 mg administered SC; Alirocumab 100 mg administered SC; Placebo administered SC
Intervention MeSH terms: Evolocumab; Alirocumab; Antibodies, Monoclonal
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be randomized to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab or alirocumab) or placebo
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: Pharmacokinetics; Pharmacodynamics