BACKGROUND Amlitelimab, a fully human nondepleting monoclonal antibody 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 (NCT05131477), patients received subcutaneous amlitelimab every 4 weeks at doses of 250 mg with 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 withdraw amlitelimab or continue the previous dose regimen for 28 weeks. The primary end point was percent change in Eczema Area and Severity Index (EASI) from baseline to Week 16. RESULTS 390 and 190 patients enrolled in Part 1 and Part 2, respectively. Significant percent change decreases in EASI were observed with amlitelimab vs. placebo (P<.001). Clinical responses at Week 24 (Investigator Global Assessment 0/1 and/or EASI-75) were maintained at Week 52 in patients continuing or withdrawn from amlitelimab. In patients maintaining clinical response at Week 52 while off-treatment, >80% had serum amlitelimab concentrations below a 4-μg/mL threshold for several weeks prior to 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 after amlitelimab withdrawal for 28 weeks.

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 配体的全人非消耗性单克隆抗体，可以预防特应性皮炎 （AD） 中出现的 T 细胞驱动的炎症。目的 本试验评估了 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 （NCT05131477） 中，患者每 4 周接受一次皮下注射 amlitelimab，剂量为 250 mg，负荷剂量为 500 mg、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用 amlitelimab 或继续之前的剂量方案 28 周。主要终点是湿疹面积和严重程度指数 （EASI） 从基线到第 16 周的百分比变化。结果 第 1 部分和第 2 部分分别有 390 名和 190 名患者入组。与安慰剂相比，观察到 amlitelimab 的 EASI 百分比变化显著降低 （P<.001）。在第 52 周继续或停用 amlitelimab 的患者中，第 24 周的临床反应 （研究者整体评估 0/1 和/或 EASI-75） 保持不变。在停止治疗期间第 52 周保持临床反应的患者中，>80% 在第 52 周前的几周内血清 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，并且在第 52 周之前在 AD 成人患者中耐受性良好。大多数患者在 amlitelimab 停药 28 周后观察到持续反应。