Abstract
INTRODUCTION: Mirikizumab, a p19-directed antibody against interleukin-23 (IL-23), is administered by subcutaneous (SC) injection. Injection site pain (ISP) associated with citrate buffers may negatively affect patient adherence to SC-administered treatments. We assessed the bioequivalence and safety of the citrate-free (CF) and original formulations of mirikizumab. METHODS: The formulations were assessed in three phase 1, two-arm, randomized, single-dose, parallel design studies in healthy participants: study A (NCT04548219), study B (NCT05515601), and study C (NCT05644353). Participants were randomized 1:1 to either formulation, then further randomized to injection site locations of abdomen, arm, or thigh. The relative bioavailability (RBA) study A had a primary objective of assessing the RBA of a single 200 mg dose. Bioequivalence (BE) studies B and C had the primary objective of assessing the BE of a 200 and 300 mg dose, respectively. In all studies, the primary endpoints were C(max), AUC(0-∞), and AUC(0-t(last)). The secondary objective was to assess safety and tolerability by treatment-emergent adverse events and serious adverse events. In study A, ISP was quantified prospectively using the 100-mm validated visual analogue scale (VAS) assessment form. RESULTS: The primary objective was met in all studies. The RBA study found no significant difference in exposure between the formulations. BE was demonstrated between CF and original mirikizumab in both BE studies, with the 90% confidence intervals of the ratios of geometric least squares means within the pre-specified equivalence limits of 0.80 and 1.25. The frequency of ISP and injection site reactions (ISRs) was lower for CF than original mirikizumab in all studies. Furthermore, a significant difference in mean VAS score was observed in study A. CONCLUSION: Mirikizumab CF and original formulations were bioequivalent. The CF formulation was associated with less pain and fewer ISRs, with no other notable differences in safety profiles. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04548219, NCT05515601, NCT05644353.