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 parameter endpoints are Cmax and AUC(0-∞) for bevacizumab. The secondary PK
      endpoints will include all other PK parameters for bevacizumab, including tmax, t1/2, CL and
      AUC(0-t).

      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 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
      (CI) 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% 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 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 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 (NAB) before the dose of MB02, EU Avastin®, or US Avastin®
      (Day -1) and at scheduled postdose 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®; US licenced 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
Intervention MeSH terms: Bevacizumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Other