Roche Products Limited, Welwyn Garden City, UK.
Genentech, Inc., South San Francisco, CA, USA.
Adv Ther. 2021 May;38(5):2406-2417. doi: 10.1007/s12325-021-01651-8. Epub 2021 Mar 29.
Etrolizumab is a novel, dual-action, anti-β7 integrin antibody in development for patients with moderate to severe ulcerative colitis or Crohn's disease. Phase 3 studies use a prefilled syringe (PFS) for etrolizumab administration. In parallel, an autoinjector (AI) is being developed to increase delivery options for patients if etrolizumab is approved. Here we describe the overall development strategy and detail the first-in-human study of this AI.
This open-label study of healthy volunteers evaluated the tolerability and usability of the etrolizumab AI under development. The primary endpoint was the proportion of participants with greater than mild pain following injection. Adverse events (AEs) and usage errors were also assessed. Results were reported by injection site (thigh vs abdomen) and needle training (experienced vs naive). Pharmacokinetic (PK) variability between participants was an exploratory endpoint.
Thirty participants completed the study; 97% of them did not experience any pain greater than mild, and 50% did not experience any pain at all. Three usage errors were observed, one of which resulted in delivery of a partial dose of etrolizumab. No patterns of usage errors were observed. Mild injection site reactions (ISRs) were reported; all resolved by the end of the study. Participants injecting into the abdomen reported more ISRs than those injecting into the thigh; needle training did not influence AE incidence or severity.
Results from this first-in-human study demonstrate that single injections of etrolizumab 105 mg using an AI were well tolerated in healthy volunteers, with transient, mild pain and minimal usage errors. Results from this study also informed the design of a subsequent PK comparability study evaluating exposure of etrolizumab administered by either the PFS or the AI. Overall, the availability of an AI may provide an attractive option for patients desiring a convenient, easy-to-use delivery mechanism for etrolizumab.
NCT02629744.
依特罗珠单抗是一种新型的、双作用的抗β7 整合素抗体，目前正在开发中，用于治疗中度至重度溃疡性结肠炎或克罗恩病患者。3 期研究使用预充式注射器（PFS）来管理依特罗珠单抗。同时，正在开发一种自动注射器（AI），如果依特罗珠单抗获得批准，将为患者提供更多的给药选择。本文介绍了这种 AI 的总体开发策略，并详细描述了其首次人体研究。
这项健康志愿者的开放标签研究评估了正在开发中的依特罗珠单抗 AI 的耐受性和易用性。主要终点是注射后出现中度以上疼痛的参与者比例。还评估了不良事件（AE）和使用错误。结果按注射部位（大腿与腹部）和针头培训（有经验与无经验）进行报告。参与者之间的药代动力学（PK）变异性是一个探索性终点。
30 名参与者完成了这项研究；97%的参与者没有出现任何中度以上的疼痛，50%的参与者根本没有出现任何疼痛。观察到 3 例使用错误，其中 1 例导致依特罗珠单抗的部分剂量给药。没有观察到使用错误的模式。报告了轻微的注射部位反应（ISR）；所有反应均在研究结束时得到解决。与大腿注射相比，腹部注射的参与者报告了更多的 ISR；针头培训不影响 AE 的发生率或严重程度。
这项首次人体研究的结果表明，在健康志愿者中，使用 AI 单次注射 105mg 依特罗珠单抗具有良好的耐受性，仅有短暂的、轻度的疼痛和最小的使用错误。这项研究的结果还为随后的 PK 可比性研究提供了信息，该研究评估了使用 PFS 或 AI 给药时依特罗珠单抗的暴露情况。总的来说，AI 的可用性可能为希望使用方便易用的给药机制的患者提供了一个有吸引力的选择。
NCT02629744。
