Comparable Pharmacokinetics, Safety, and Tolerability of Etrolizumab Administered by Prefilled Syringe or Autoinjector in a Randomized Trial in Healthy Volunteers

Abstract

Introduction: Etrolizumab is a novel, dual-action anti-β7 integrin antibody studied in phase 3 trials in patients with inflammatory bowel disease. An autoinjector (AI) is being developed in parallel to complement the prefilled syringe with needle safety device (PFS-NSD) for subcutaneous (SC) administration in these trials. Here we demonstrate the comparable pharmacokinetics, tolerability, and safety of both devices.

Methods: This randomized, open-label, two-part study in healthy participants evaluated the comparability of etrolizumab exposure between the AI and the PFS-NSD. Part 1 (pilot) involved a small number of participants, and initial results were used to finalize the design of the larger part 2 (pivotal) study. In both parts, participants were randomly assigned to receive a single SC dose of etrolizumab 105 mg by AI or PFS-NSD. Randomization was stratified by body weight. Primary pharmacokinetic outcomes were C_max, AUC_last, and AUC_0-inf.

Results: One hundred and eighty healthy participants (part 1, n = 30; part 2, n = 150) received a single SC dose of etrolizumab by AI or PFS-NSD. Primary pharmacokinetic results from part 1 supported modification of the part 2 study design. Results from part 2 demonstrated that etrolizumab exposure was equivalent between devices, with geometric mean ratios (GMRs) between AI and PFS-NSD of 102% (90% confidence interval [CI] 94.2-111) for C_max, 98.0% (90% CI 89.3-107) for AUC_last, and 97.6% (90% CI 88.6-107) for AUC_0-inf. Median t_max and mean terminal t_1/2 were also similar between devices. GMRs and 90% CIs of all primary pharmacokinetic parameters were fully contained within the predefined equivalence limits (80-125%).

Conclusion: This pharmacokinetic study demonstrated that single SC injections of etrolizumab 105 mg using an AI or a PFS-NSD resulted in equivalent etrolizumab exposure and similar safety and tolerability in healthy participants. Taken together, these results support the use of an AI for etrolizumab administration.

Trial registration: NCT02996019.

Keywords: Auto-injector; Crohn’s disease; Etrolizumab; Inflammatory bowel disease; Pharmacokinetic comparability; Prefilled syringe; Ulcerative colitis.