Clinical trial NCT04238663
Conditions: Healthy Volunteers
Sponsor: mAbxience Research S.L.
Start date: 2019-09-24; Completion date: 2020-03-17
Enrollment: 115 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. arm 2: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. arm 3: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
Interventions: intervention 1: MB02 (Bevacizumab Biosimilar) intervention 2: EU approved Avastin® intervention 3: US licenced Avastin®
Intervention descriptions: intervention 1: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion intervention 2: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion intervention 3: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion

Protocol documents:
Prot_002.pdf: 
 
Protocol Title: 
A Randomised, Double Blind, Three-Arm, Single 
Dose, Parallel Study To Compare the 
Pharmacokinetics, Safety and Immunogenicity of 
MB02 (Bevacizumab Biosimilar Drug), US licenced 
Avastin® and EU approved Avastin® in Healthy 
Male Volunteers 
NCT Number: 
NCT04238663 
Protocol version 
date: 
Version 7.0, 24 Jan 2020 
 










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SAP_003.pdf: 
 
Protocol Title: 
A Randomized, Double Blind, Three-Arm, Single 
Dose, Parallel Study To Compare the 
Pharmacokinetics, Safety and Immunogenicity of 
MB02 (Bevacizumab Biosimilar Drug), US licensed 
Avastin® and EU approved Avastin® in Healthy 
Male Volunteers 
NCT Number: 
NCT04238663 
SAP version 
date: 
Version 2.0, 09 Mar 2020