A Pharmacokinetic Study Comparing MB02 And EU Avastin® In Healthy Male Volunteers
Condition: Healthy Volunteers; Male; Japanese
Study type: Interventional
Phase: Phase 1

Summary: 
      A Randomised, Double Blind, Two-Arm, Single Dose, Parallel Phase I Study To Compare the
      Pharmacokinetics, Safety and Immunogenicity of MB02 (a Proposed Bevacizumab Biosimilar Drug)
      and EU Approved Avastin® in Japanese Healthy Male Volunteers.

      During the course of the study, the similarity in pharmacokinetics will be assessed by
      sampling the levels of drug in the blood, and by comparing these levels among the different
      administration arms. Safety, tolerability, and immunologic response to the administered drugs
      will also be evaluated throughout.
    

Detailed description: 
      The primary PK parameter endpoint is AUC(0-∞) for bevacizumab. The secondary PK endpoints
      will include all other PK parameters for bevacizumab, including Cmax, tmax, t1/2, CL and
      AUClast.

      The serum PK parameters of bevacizumab will be calculated using standard noncompartmental
      methods. An analysis of covariance model will be used to analyse the log-transformed primary
      PK parameters (AUC[0-∞] and Cmax) and AUClast. The model will include a fixed effect for
      treatment and body weight as a covariate.

      All other PK parameters will not be subject to inferential statistical analysis.

      Estimates of geometric mean ratios together with the corresponding 90% confidence intervals
      (CI) will be derived for the comparisons of the PK parameters as follows:

      • MB02 versus EU Avastin®

      A mixed effects model with treatment arm as fixed effect will be used to compare
      natural-logarithmic transformed PK parameters (AUC[0-∞+, AUClast and Cmax) between the two
      treatment arms (MB02 vs EU-approved Avastin®)

      PK similarity between arms will be concluded if the 90% confidence intervals (CIs) for the
      geometric mean test/reference ratio of AUC(0-∞) fell within the predefined 0.80-1.25
      bioequivalence interval.

      All AEs will be listed and summarised using descriptive methodology. All observed or
      patient-reported AEs will be graded by the National Cancer Institute Common Terminology
      Criteria for Adverse Events version 5.0. The incidence of AEs for each treatment will be
      presented by severity and by association with the study drugs as determined by the
      Investigator (or designee). Each AE will be coded using the Medical Dictionary for Regulatory
      Activities. All safety data will be listed and summarised as appropriate.

      Immunogenicity data (overall ADA incidence and titers, and neutralising ADA results) will be
      listed. A summary of the number and percent of subjects testing positive for ADA or
      neutralising antibodies before the dose of MB02, EU Avastin® (Day -1) and at scheduled
      post-dose assessments will be presented by treatment arm. All safety data and immunogenicity
      data summaries will be based on the safety analysis population. Select analyses may be
      repeated for subsets with or without ADA and de novo ADA formation as appropriate.
    

Intervention name(s): MB02 (Bevacizumab Biosimilar); EU approved Avastin®
Intervention type(s): Drug; Drug
Intervention description(s): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion; Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Intervention MeSH terms: Bevacizumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Other