A randomized, single-blind, Phase I trial (INVICTAN-1) assessing the bioequivalence and safety of BI 695502, a bevacizumab biosimilar candidate, in healthy subjects

ABSTRACT

Objectives: This Phase I trial (INVICTAN®-1) evaluated three-way bioequivalence and safety of BI 695502 a bevacizumab biosimilar candidate, and reference product bevacizumab from two sources (US-approved Avastin®, Genentech; EU-approved Avastin, Roche).

Methods: Healthy male subjects (N = 91) were randomized 1:1:1 to receive a single intravenous infusion of 1 mg/kg of BI 695502 or US- or EU-approved Avastin. An interim analysis was planned when ~50% of subjects were evaluable for the primary end point to determine if the prespecified criteria for bioequivalence were achieved; if demonstrated, the study could be stopped early. The primary end point was area under the concentration–time curve (AUC) of the analyte in plasma from time zero extrapolated to infinity (AUC_0–∞). Other pharmacokinetic (PK) parameters, safety, and in vitro binding affinity were also evaluated.

Results: The interim analysis demonstrated three-way bioequivalence for all comparisons. The confidence intervals around the geometric mean ratios of the primary and secondary PK parameters were within the predefined acceptance ranges. Study drugs were well tolerated with no clinically relevant differences in safety.

Conclusion: BI 695502 and US- and EU-approved Avastin showed three-way bioequivalence with similar safety profile.

Clinical trial registration: NCT01608087.

KEYWORDS:

• Bevacizumab
• BI 695502
• bioequivalence
• biosimilar
• pharmacokinetics

Acknowledgments

C. Wynne was an investigator in the trial and provided a critical review of the manuscript. W. Hettema, B. Lang, M. Altendorfer, N. Czeloth, R. Lohmann, S. Athalye, and D. Schliephake were responsible for the interpretation of the trial data and provided critical reviews throughout the development of this manuscript. All authors have approved the final manuscript for submission. Medical writing support was provided by SciMentum, UK, and GeoMed, an Ashfield company, part of UDG Healthcare plc, UK, and funded by Boehringer Ingelheim.

Trial registration number: NCT01608087.

Declaration of interest

C. Wynne is an employee of, and holds shares in, an organization that received payment for carrying out the trial. B. Lang, M. Altendorfer, N. Czeloth, R. Lohmann, and D. Schliephake are employees of Boehringer Ingelheim. S. Athalye and W. Hettema were employees of Boehringer Ingelheim at the time this trial was performed and when this publication was initiated.

Additional information

Funding

This study was funded by Boehringer Ingelheim.