Genentech, Inc., South San Francisco, CA, USA.
Roche Products Limited, Welwyn Garden City, UK.
Adv Ther. 2021 May;38(5):2418-2434. doi: 10.1007/s12325-021-01661-6. Epub 2021 Mar 29.
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.
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, AUC, and AUC.
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, 98.0% (90% CI 89.3-107) for AUC, and 97.6% (90% CI 88.6-107) for AUC. Median t and mean terminal t were also similar between devices. GMRs and 90% CIs of all primary pharmacokinetic parameters were fully contained within the predefined equivalence limits (80-125%).
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.
NCT02996019.
依特罗珠单抗是一种新型的双作用抗β7 整联蛋白抗体，已在炎症性肠病患者的 3 期临床试验中进行研究。正在开发一种自动注射器（AI），以与带针头安全装置的预填充注射器（PFS-NSD）配套使用，用于这些试验中的皮下（SC）给药。在这里，我们证明了这两种设备具有相当的药代动力学、耐受性和安全性。
这项在健康参与者中进行的随机、开放标签、两部分研究评估了 AI 和 PFS-NSD 之间依特罗珠单抗暴露的可比性。第 1 部分（试点）涉及少数参与者，最初的结果用于最终确定更大的第 2 部分（关键）研究的设计。在两部分中，参与者被随机分配接受 AI 或 PFS-NSD 单次 SC 剂量的 105mg 依特罗珠单抗。随机分组按体重分层。主要药代动力学结果为 C、AUC 和 AUC。
180 名健康参与者（第 1 部分，n=30；第 2 部分，n=150）接受了 AI 或 PFS-NSD 单次 SC 剂量的依特罗珠单抗。第 1 部分的主要药代动力学结果支持对第 2 部分研究设计的修改。第 2 部分的结果表明，两种装置之间的依特罗珠单抗暴露相当，AI 与 PFS-NSD 的几何均数比（GMR）分别为 C（90%置信区间[CI]为 94.2-111）、AUC（90%CI 为 89.3-107）和 AUC（97.6%[88.6-107]）。两种装置的中位 t 和平均终末 t 也相似。所有主要药代动力学参数的 GMR 和 90%CI 均完全包含在预设的等效限度（80-125%）内。
这项药代动力学研究表明，健康参与者单次 SC 注射 105mg 依特罗珠单抗，使用 AI 或 PFS-NSD 可产生相当的依特罗珠单抗暴露，安全性和耐受性相似。这些结果共同支持使用 AI 进行依特罗珠单抗给药。
NCT02996019。
