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

Summary: 
      Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare
      the Pharmacokinetics (PK), safety and immunogenicity profile of MB02 with US and EU Avastin®
      in healthy male subjects.

      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 parameters are Cmax and AUC(0-∞). The PK parameters for 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 AUC(0-t).
      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 will be
      derived for the comparisons of the PK parameters as follows:

        -  MB02 versus EU Avastin®

        -  MB02 versus US Avastin®

        -  EU Avastin® versus US Avastin®

      PK similarity will be achieved if the 90% confidence intervals (CIs) for the
      biosimilar-to-reference ratios of PK endpoints (AUC[0-∞] and Cmax) fall within the predefined
      0.80-1.25 acceptance similarity criteria for all 3 pairwise comparisons; MB02 versus
      EU-approved Avastin®; MB02 versus US-licenced Avastin®; and EU-approved Avastin® versus
      US-licenced Avastin®.

      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 (CTCAE) version 4.03. 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). All safety data will be listed and summarised as appropriate

      Immunogenicity data (overall anti-drug antibody [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®, or US Avastin® (Day
      1) and at scheduled postdose assessments will be presented by treatment arm.
    

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