TROIKA-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.

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 AUC0-inf and secondary PK endpoints, AUC0-last and Cmax 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 AUC0-inf , Cmax and AUC0-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.

Demarchi M ，Coliat P ，Mclendon K ，Chung Shii Hii J ，Feyaerts P ，Ang F ，Jaison L ，Deforce F ，Derde MP ，Kim MJ ，Park LS ，Detappe A ，Pivot X ... -  《Pharmacology Research & Perspectives》

A Randomized Phase I Study Comparing the Pharmacokinetics of HD201, a Trastuzumab Biosimilar, With European Union-sourced Herceptin.

This first-in-human study of HD201 was designed to evaluate the pharmacokinetic (PK) equivalence between this biosimilar candidate and trastuzumab sourced in the European Union (EU-trastuzumab)*. In this randomized, blinded, single-dose comparative PK study, healthy male subjects were randomized to receive a single 6 mg/kg IV dose of HD201 or EU-trastuzumab. The primary PK end point was AUC0-∞. Equivalence was determined by using the predefined margins of 0.8 to 1.25. Other PK parameters were included as secondary end points. Baseline demographic characteristics for the 73 randomized subjects were similar across the 2 groups: median age 29 and 30 years old (ranges 19 - 45), median weight 78.6 and 81.7 kg (ranges 60.2 - 101). The 90% CIs for the geometric least squares mean of the AUC0-∞ were included within the margins of 0.8 to 1.25. All other PK parameters were comparable for both HD201 and EU-trastuzumab. The proportions of subjects who experienced adverse events related to the study drug were 61.8% and 82.9% in the HD201 and EU-trastuzumab groups, respectively. The most frequently reported adverse events related to the study drug were infusion-related reactions. No subjects had positive results for antidrug antibodies after a single dose. This study reported the PK equivalence between HD201 and EU-trastuzumab. HD201 was well tolerated with no safety concerns after single-dose administration in healthy male subjects. EudraCT No.: 2012-000805-56.

Pivot X ，Deslypere JP ，Park LS ，Kim MJ ，Lee W ，Lee J ... -  《-》

A randomized Phase I pharmacokinetic trial comparing the potential biosimilar trastuzumab (SIBP-01) with the reference product (Herceptin®) in healthy Chinese male volunteers.

Zhou H ，Cao S ，Zhu X ，Xie J ，Fan L ，Ge Q ，Wang Y ，Zhu J ，Liu Y ，Shao Z ，Shan R ，Liu B ，Wang H ，Ding L ... -  《-》

A Randomized Phase I Pharmacokinetic Study Comparing Biosimilar Candidate SB3 and Trastuzumab in Healthy Male Subjects.

This first-in-human study with SB3 was designed to evaluate the pharmacokinetic (PK) equivalence between SB3 and trastuzumab sourced in the European Union (EU trastuzumab), between SB3 and trastuzumab sourced in the United States (US trastuzumab), and between EU and US trastuzumab (NCT02075073). In this randomized, double-blind, parallel group, single-dose comparative PK study, 109 healthy male subjects were randomized to receive a single 6-mg/kg IV dose of SB3, EU -trastuzumab, or US trastuzumab. The PK parameters were calculated using noncompartmental methods. The PK equivalence in terms of AUC0--∞), AUC0-last, and Cmax for the pairwise comparisons (SB3 vs EU trastuzumab, SB3 vs US trastuzumab, and EU trastuzumab vs US trastuzumab) were determined using the predefined equivalence margin of 0.8 to 1.25. Baseline demographic characteristics for the randomized subjects were similar across the 3 groups. The 90% CIs for the geometric least square means of the AUC0-∞, AUC0-last, and Cmax were completely contained within the margin of 0.8 to 1.25. The proportions of subjects who experienced adverse events related to the study drug were 36.1%, 44.4%, and 61.1% in the SB3, EU trastuzumab, and US trastuzumab groups, respectively. The most frequently reported adverse events related to the study drug was infusion-related reactions. No subjects had positive results for antidrug antibodies after a single dose of SB3, EU trastuzumab, or US trastuzumab. This study revealed PK equivalence between SB3 and EU trastuzumab, between SB3 and US trastuzumab, and between EU trastuzumab and US trastuzumab. SB3 is well tolerated without tolerability concerns after single-dose administration in healthy male subjects.

Pivot X ，Curtit E ，Lee YJ ，Golor G ，Gauliard A ，Shin D ，Kim Y ，Kim H ，Fuhr R ... -  《-》

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

Farmahini Farahani M ，Maghzi P ，Jafari Aryan N ，Payandemehr B ，Soni M ，Azhdarzadeh M ... -  《-》