Advances in therapy · 2025
Pharmacokinetic Bridging Between an Autoinjector and a Prefilled Syringe Following Subcutaneous Administration of Mirikizumab in Healthy Participants.
СтатьяРандомизированное исследованиеКлиническое исследование I фазыНазвание и аннотация: Перевод пока не подготовлен
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Zhang Xin, Otani Yuki, Payne Christopher D, Morris Nathan J, Chua Laiyi, Escobar Rodrigo, Wang Sihe, Shi Galen
Аннотация
INTRODUCTION: Mirikizumab, a humanized anti-interleukin-23p19 monoclonal antibody, is approved for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). Two phase 1, open-label, two-arm, randomized studies compared pharmacokinetics and safety of mirikizumab (200 mg, Study AMBW; 300 mg, Study AMBX) to establish bioequivalence. Mirikizumab was administered subcutaneously using an autoinjector or a prefilled syringe (PFS) as a single dose in healthy participants.
METHODS: Participants (male and female) were randomized 1:1 to mirikizumab by a PFS (reference) and an autoinjector (test). Participants were sub-randomized (1:1:1) to one of three injection sites (abdomen, arm, thigh) and stratified into one of three weight groups. Primary endpoints were maximum observed drug concentration (Cmax), and area under concentration versus time curves (time zero to infinity [AUC0-∞]; time to last time point with measurable concentration [AUC0-tlast]). Secondary objectives were safety and immunogenicity.
RESULTS: In Study AMBW, 90% confidence intervals (CIs) for the ratios (autoinjector to PFS) of geometric least squares mean values for Cmax, AUC0-∞, and AUC0-tlast were within prespecified bioequivalence limits (0.80-1.25). Similar results were observed in Study AMBX, after administration of mirikizumab 300 mg, with bioequivalence achieved for AUC0-tlast and AUC0-∞, while the upper bound of the 90% CI of the geometric least squares mean ratio for Cmax was slightly above the bioequivalence upper threshold. Overall safety of mirikizumab was similar between devices in both studies. Immunogenicity was similar overall in Study AMBW, but slightly higher (autoinjector versus PFS) in Study AMBX.
CONCLUSION: Mirikizumab administered by autoinjector or PFS was considered bioequivalent at the 200-mg UC maintenance dose and the 300-mg CD maintenance dose. Safety and immunogenicity profiles were comparable between autoinjector and PFS. Availability of an autoinjector option may be preferred by some patients and may help improve patient adherence to treatment.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04607733; NCT05069896.
METHODS: Participants (male and female) were randomized 1:1 to mirikizumab by a PFS (reference) and an autoinjector (test). Participants were sub-randomized (1:1:1) to one of three injection sites (abdomen, arm, thigh) and stratified into one of three weight groups. Primary endpoints were maximum observed drug concentration (Cmax), and area under concentration versus time curves (time zero to infinity [AUC0-∞]; time to last time point with measurable concentration [AUC0-tlast]). Secondary objectives were safety and immunogenicity.
RESULTS: In Study AMBW, 90% confidence intervals (CIs) for the ratios (autoinjector to PFS) of geometric least squares mean values for Cmax, AUC0-∞, and AUC0-tlast were within prespecified bioequivalence limits (0.80-1.25). Similar results were observed in Study AMBX, after administration of mirikizumab 300 mg, with bioequivalence achieved for AUC0-tlast and AUC0-∞, while the upper bound of the 90% CI of the geometric least squares mean ratio for Cmax was slightly above the bioequivalence upper threshold. Overall safety of mirikizumab was similar between devices in both studies. Immunogenicity was similar overall in Study AMBW, but slightly higher (autoinjector versus PFS) in Study AMBX.
CONCLUSION: Mirikizumab administered by autoinjector or PFS was considered bioequivalent at the 200-mg UC maintenance dose and the 300-mg CD maintenance dose. Safety and immunogenicity profiles were comparable between autoinjector and PFS. Availability of an autoinjector option may be preferred by some patients and may help improve patient adherence to treatment.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04607733; NCT05069896.