Pharmacodynamic Biomarkers to Support Biosimilar Development: Interleukin-5 Antagonists
Condition: Healthy Subjects; Pharmacokinetics; Pharmacodynamics
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is designed to assess pharmacokinetics and pharmacodynamics of mepolizumab and
      reslizumab 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 (mepolizumab or reslizumab) or placebo.
    

Detailed description: 
      This study is designed to assess pharmacokinetics and pharmacodynamics of mepolizumab and
      reslizumab 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 (mepolizumab or reslizumab) or placebo. Mepolizumab doses are 3, 6, 12, or
      24 mg. Reslizumab doses are 0.1, 0.2, 0.4, or 0.8 mg/kg. 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 two
      weeks and continue follow-up through either day 63 or day 123.

      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 determination
      of eosinophil counts (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): Mepolizumab; Mepolizumab; Mepolizumab; Mepolizumab; Reslizumab; Reslizumab; Reslizumab; Reslizumab; Placebo
Intervention type(s): Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological
Intervention description(s): Mepolizumab 3 mg administered SC; Mepolizumab 6 mg administered SC; Mepolizumab 12 mg administered SC; Mepolizumab 24 mg administered SC; Reslizumab 0.1 mg/kg administered IV; Reslizumab 0.2 mg/kg administered IV; Reslizumab 0.4 mg/kg administered IV; Reslizumab 0.8 mg/kg administered IV; Placebo (administered either IV or SC)
Intervention MeSH terms: Reslizumab
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 (mepolizumab or reslizumab) or placebo
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: Pharmacokinetics; Pharmacodynamics