Open AccessTROIKA‐1: A double‐blind, randomized, parallel group, study aimed to demonstrate the equivalent pharmacokinetic profile of HD201, a potential biosimilar candidate to trastuzumab, versus EU‐Herceptin ® and US‐Herceptin ® in healthy male subjects
Author(s) -
Demarchi Martin,
Coliat Pierre,
Mclendon Kristi,
Chung Shii Hii Jocelyn,
Feyaerts Peggy,
Ang Felicia,
Jaison Litha,
Deforce Filip,
Derde Marie Paule,
Kim Michael Jinwoo,
Park Lisa Soyeon,
Detappe Alexandre,
Pivot Xavier
Publication year - 2021
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.839
Subject(s) - biosimilar , medicine , tolerability , bioequivalence , pharmacokinetics , trastuzumab , clinical endpoint , confidence interval , pharmacology , dosing , randomized controlled trial , adverse effect , oncology , breast cancer , cancer
Prestige Biopharma Ltd (Singapore) has developed HD201, a proposed biosimilar to reference product trastuzumab. As a part of the stepwise approach to ensure comparability between the biosimilar candidate and the reference medicinal product, a phase I study in healthy subjects was conducted to demonstrate the pharmacokinetic (PK) equivalence (NCT03776240). The primary objective of the study was to demonstrate (PK) equivalence of HD201, EU‐Herceptin ® , and US‐Herceptin ® given at 6 mg/kg as a 90‐min i.v. infusion to healthy male subjects. A pairwise comparisons based on the primary endpoint AUC 0–inf and secondary PK endpoints, AUC 0–last and C max were undertaken. PK equivalence was to be concluded if the 90% confidence interval (CI) for the ratio of geometric means for each criterion were within the equivalence margin of 80% to 125%. Secondary objectives included assessment of other PK parameters, safety, tolerability, and immunogenicity in the three arms. A total of 105 healthy male subjects (35/treatment) were randomized in this study. The 90% CI for the ratios of AUC 0–inf , C max and AUC 0–last , were within 80%–125% for the comparisons of HD201 to EU‐Herceptin ® or US‐Herceptin ® and EU‐Herceptin ® to US‐Herceptin ® . The frequency of subjects with TEAEs of special interest was slightly lower in the HD201 group (20.0%) compared to the other treatment groups (EU‐Herceptin ® : 34.3%; US‐Herceptin ® : 31.4%). Only 1 subject (EU‐Herceptin ® group) developed anti‐drug antibodies prior to dosing. Overall, HD201 demonstrates PK similarity to both EU‐Herceptin ® and US‐Herceptin ® . The three study drugs also demonstrated similar safety profiles.