BACKGROUND Amlitelimab, a fully human nondepleting mAb targeting OX40 ligand on antigen-presenting cells, could prevent T-cell-driven inflammation seen in atopic dermatitis (AD). OBJECTIVE This trial evaluated the efficacy and safety of amlitelimab in adults with AD. METHODS In this 2-part, phase 2b, randomized, double-blinded placebo-controlled trial (ClinicalTrials.gov identifier NCT05131477), patients received subcutaneous amlitelimab every 4 weeks at doses of 250 mg plus a 500-mg loading dose, 250 mg, 125 mg, or 62.5 mg or placebo for 24 weeks in Part 1 (1:1:1:1:1 randomization). In Part 2, clinical responders were reallocated 3:1 to stop taking amlitelimab or continue the previous dose regimen for 28 weeks. The primary end point was percentage of change in Eczema Area and Severity Index (EASI) from baseline to week 16. RESULTS In all, 390 and 190 patients enrolled in Part 1 and Part 2, respectively. A significant percentage of change decrease in EASI was observed with amlitelimab doses versus with placebo (P < .001). Clinical responses at week 24 (Investigator Global Assessment 0/1 and/or a 75% reduction in EASI) were maintained at week 52 in patients continuing or stopping amlitelimab. Of the patients maintaining clinical response at week 52 after no longer receiving treatment, more than 80% had serum amlitelimab concentrations less than the 4-μg/mL threshold for several weeks before week 52. Reductions in AD-related biomarkers during Part 1 were maintained through Part 2. Amlitelimab was well tolerated over 52 weeks. CONCLUSIONS Amlitelimab treatment significantly reduced clinical and biomarker responses, and was well tolerated in adults with AD through week 52. Sustained responses were observed in the majority of patients for 28 weeks after they had stopped taking amlitelimab.

中文翻译：

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amlitelimab（一种抗 OX40 配体抗体）在中度至重度特应性皮炎患者中的 2b 期随机临床试验。


背景 Amlitelimab 是一种靶向抗原呈递细胞上 OX40 配体的全人非消耗型 mAb，可以预防特应性皮炎 （AD） 中常见的 T 细胞驱动炎症。目的 该试验评估了 amlitelimab 在成人 AD 患者中的疗效和安全性。方法 在这项分为 2 部分的 2b 期随机、双盲安慰剂对照试验 （ClinicalTrials.gov 标识符 NCT05131477） 中，患者每 4 周接受一次皮下注射 amlitelimab，剂量为 250 mg 加 500 mg 负荷剂量、250 mg、125 mg 或 62.5 mg 或安慰剂，持续 24 周在第 1 部分中（1：1：1：1：1：1 随机化）。在第 2 部分中，临床反应者以 3：1 的比例重新分配以停止服用 amlitelimab 或继续之前的剂量方案 28 周。主要终点是从基线到第 16 周湿疹面积和严重程度指数 （EASI） 的变化百分比。结果 总共有 390 名和 190 名患者分别参加了第 1 部分和第 2 部分。与安慰剂相比，观察到 amlitelimab 剂量的 EASI 变化减少的显着百分比 （P < .001）。对于继续或停用 amlitelimab 的患者，第 24 周时的临床反应 （研究者整体评估 0/1 和/或 EASI 降低 75%） 维持在第 52 周。在不再接受治疗后第 52 周维持临床反应的患者中，超过 80% 的患者在第 52 周前数周血清 amlitelimab 浓度低于 4 μg/mL 阈值。第 1 部分期间 AD 相关生物标志物的减少一直维持到第 2 部分。Amlitelimab 在 52 周内耐受性良好。结论 Amlitelimab 治疗显著降低了临床和生物标志物反应，并且在 AD 成人患者中到第 52 周耐受性良好。 大多数患者在停止服用 amlitelimab 后 28 周内观察到持续反应。