Xin Zhang, Yuki Otani, Christopher D Payne, Nathan J Morris, Laiyi Chua, Rodrigo Escobar, Sihe Wang, Galen Shi
{"title":"在健康受试者中皮下给药Mirikizumab后，自动注射器和预充注射器之间的药代动力学桥接。","authors":"Xin Zhang, Yuki Otani, Christopher D Payne, Nathan J Morris, Laiyi Chua, Rodrigo Escobar, Sihe Wang, Galen Shi","doi":"10.1007/s12325-025-03335-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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 (C<sub>max</sub>), and area under concentration versus time curves (time zero to infinity [AUC<sub>0-∞</sub>]; time to last time point with measurable concentration [AUC<sub>0-tlast</sub>]). Secondary objectives were safety and immunogenicity.</p><p><strong>Results: </strong>In Study AMBW, 90% confidence intervals (CIs) for the ratios (autoinjector to PFS) of geometric least squares mean values for C<sub>max</sub>, AUC<sub>0-∞</sub>, and AUC<sub>0-tlast</sub> 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 AUC<sub>0-tlast</sub> and AUC<sub>0-∞</sub>, while the upper bound of the 90% CI of the geometric least squares mean ratio for C<sub>max</sub> 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov NCT04607733; NCT05069896.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetic Bridging Between an Autoinjector and a Prefilled Syringe Following Subcutaneous Administration of Mirikizumab in Healthy Participants.\",\"authors\":\"Xin Zhang, Yuki Otani, Christopher D Payne, Nathan J Morris, Laiyi Chua, Rodrigo Escobar, Sihe Wang, Galen Shi\",\"doi\":\"10.1007/s12325-025-03335-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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 (C<sub>max</sub>), and area under concentration versus time curves (time zero to infinity [AUC<sub>0-∞</sub>]; time to last time point with measurable concentration [AUC<sub>0-tlast</sub>]). Secondary objectives were safety and immunogenicity.</p><p><strong>Results: </strong>In Study AMBW, 90% confidence intervals (CIs) for the ratios (autoinjector to PFS) of geometric least squares mean values for C<sub>max</sub>, AUC<sub>0-∞</sub>, and AUC<sub>0-tlast</sub> 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 AUC<sub>0-tlast</sub> and AUC<sub>0-∞</sub>, while the upper bound of the 90% CI of the geometric least squares mean ratio for C<sub>max</sub> was slightly above the bioequivalence upper threshold. Overall safety of mirikizumab was similar between devices in both studies. 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Pharmacokinetic Bridging Between an Autoinjector and a Prefilled Syringe Following Subcutaneous Administration of Mirikizumab in Healthy Participants.
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.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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