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

Pharmacol Res Perspect. 2021 Aug;9(4):e00839. doi: 10.1002/prp2.839.

Abstract

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.

Keywords: biosimilar; pharmacokinetic; trastuzumab.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies / blood
  • Antineoplastic Agents, Immunological / immunology
  • Antineoplastic Agents, Immunological / pharmacokinetics*
  • Area Under Curve
  • Biosimilar Pharmaceuticals / pharmacokinetics*
  • Double-Blind Method
  • Healthy Volunteers
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Trastuzumab / immunology
  • Trastuzumab / pharmacokinetics*
  • Young Adult

Substances

  • Antibodies
  • Antineoplastic Agents, Immunological
  • Biosimilar Pharmaceuticals
  • Trastuzumab

Associated data

  • ClinicalTrials.gov/NCT03776240