A randomized, double-blind, parallel pharmacokinetic study comparing the trastuzumab biosimilar candidate, AryoTrust®, and reference trastuzumab in healthy subjects

ABSTRACT

Background

AryoTrust® (AryoGen Pharmed Co., Iran) is a biosimilar candidate for the EU-sourced reference trastuzumab, Herceptin®. This study was designed to evaluate the bioequivalence between AryoTrust® and Herceptin®.

Research design and methods

In this double-blind, parallel study, 60 healthy male subjects were randomized 1:1 to receive a single dose of AryoTrust® or Herceptin® (6 mg/kg) as intravenous infusion. The primary endpoint of the study was the area under the concentration versus time to infinity (AUC_0-inf), and the main secondary endpoints were maximum measured concentration (C_max), area under the concentration versus time from zero to the last quantifiable concentration time (AUC_0-last), immunogenicity, and safety.

Results

Sixty subjects were enrolled in the study and baseline demographics were similar between the two groups. The two groups demonstrated similar pharmacokinetic parameters and the 90% confidence interval (CI) for primary and secondary endpoints were within the bioequivalence acceptance range (80.00%–125.00%). No serious adverse event or immunogenicity was reported, and all of the adverse events reported were mild and similar between the two treatment groups.

Conclusion

AryoTrust® was well tolerated, had a similar safety profile to reference trastuzumab, and its pharmacokinetic bioequivalence was confirmed.

Trial registration

The trial is registered at Indian Trials Registry (CTRI/2019/03/018218)

KEYWORDS:

• Bioequivalence
• biosimilar
• breast cancer
• drug Safety
• pharmacokinetics

Acknowledgments

The authors would like to thank all those involved in this study, including the volunteers and Cliantha Research Limited as the CRO who conducted the study. Biostatistician-Pankaj S. Hotchandani from Cliantha Research Limited was responsible for data analysis and interpretation.

Declaration of interest

The sponsor (AryoGen Pharmed Co.) has confirmed the study design by CRO of the study and respective amendments. All data related to this study were interpreted by the trial staff with complete independence from the sponsor. Morteza Azhdarzadeh, Borna Payandemehr, Parnian Maghzi, Nazanin Jafari Aryan, and Mohammad Farmahini Farahani are employees of the sponsor team. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Data Availability Statement

The data that support the findings of this study are available on reasonable request from the corresponding author (a signed data access agreement must be in place). The data are not publicly available due to confidential issues, privacy, or ethical restrictions.

Additional information

Funding

This study was fully funded by AryoGen Pharmed Co.