Spesolimab Efficacy and Safety in Patients with Moderate-to-Severe Palmoplantar Pustulosis: A Multicentre, Double-Blind, Randomised, Placebo-Controlled, Phase IIb, Dose-Finding Study,Dermatology and Therapy

当前位置： X-MOL 学术 › Dermatol. Ther. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Spesolimab Efficacy and Safety in Patients with Moderate-to-Severe Palmoplantar Pustulosis: A Multicentre, Double-Blind, Randomised, Placebo-Controlled, Phase IIb, Dose-Finding Study
Dermatology and Therapy ( IF 3.5 ) Pub Date : 2023-09-20 , DOI: 10.1007/s13555-023-01002-1
A David Burden ₁ , Robert Bissonnette ₂ , Alexander A Navarini ₃ , Masamoto Murakami ₄ , Akimichi Morita ₅ , Thomas Haeufel ₆ , Binqi Ye ₇ , Frank Baehner ₆ , Tadashi Terui ₈

Affiliation

Introduction

We evaluated the anti-interleukin-36 receptor antibody spesolimab in patients with moderate-to-severe palmoplantar pustulosis (PPP).

Methods

This phase IIb trial comprised a loading dose period to week (W) 4, then maintenance dosing to W52. Patients were randomised 2:1:1:1:2 to subcutaneous spesolimab 3000 mg to W4 then 600 mg every 4 weeks (q4w), spesolimab 3000 mg to W4 then 300 mg q4w, spesolimab 1500 mg to W4 then 600 mg q4w, spesolimab 1500 mg to W4, 300 mg q4w to W16 then 300 mg every 8 weeks (q8w), or placebo switching to spesolimab 600 mg q4w at W16. The primary efficacy endpoint was percentage change from baseline in Palmoplantar Pustular Area and Severity Index (PPP ASI) at W16. Secondary endpoints included a Palmoplantar Pustular Physician’s Global Assessment (PPP PGA) score of 0/1. Safety (including adverse events [AEs], local tolerability) was assessed.

Results

152 patients were treated. The primary endpoint was not met; mean differences for spesolimab versus placebo ranged from − 14.6% (95% confidence interval [CI]: − 31.5%, 2.2%) to − 5.3% (95% CI: − 19.1%, 8.6%); none reached significance. At W16, 23 (21.1%) and two (4.7%) patients in the combined spesolimab and placebo groups, respectively, achieved PPP PGA 0/1 (mean difference 16.4%; 95% CI: 3.8%, 25.7%), increasing to 59 (54.1%; combined spesolimab) and 12 (27.9%; placebo switch to spesolimab) patients at W52. Non-Asian patients had significant improvements in the primary endpoint (mean difference − 17.7%; nominal P = 0.0394) and PPP PGA 0/1 at W16 with spesolimab versus placebo. Rates of AEs and AE-related discontinuations were similar for spesolimab and placebo. Local tolerability events and injection-site reactions were more frequent with spesolimab than placebo.

Conclusion

The primary objective to demonstrate a non-flat dose–response relationship and proof-of-concept was not achieved; improvements with spesolimab occurred in secondary endpoints and in non-Asian patients, indicating potential modest benefits. Spesolimab was generally well tolerated (ClinicalTrials.gov NCT04015518).

中文翻译：

Spesolimab 对中重度掌跖脓疱病患者的疗效和安全性：多中心、双盲、随机、安慰剂对照、IIb 期剂量探索研究

介绍

我们评估了抗白细胞介素 36 受体抗体 spesolimab 在中重度掌跖脓疱病 (PPP) 患者中的作用。

方法

该 IIb 期试验包括至第 4 周（W）的负荷剂量期，然后至第 52 周的维持剂量。患者按 2:1:1:1:2 随机分配至皮下注射 spesolimab 3000 mg，第 4 周，然后每 4 周 600 mg（每 4 周一次），spesolimab 3000 mg，第 4 周，然后 300 mg，第 4 周，spesolimab 1500 mg，第 4 周，然后 600 mg，每 4 周一次，spesolimab第 4 周 1500 mg，第 16 周每 4 周 300 mg，然后每 8 周 300 mg (q8w)，或安慰剂在第 16 周改用 spesolimab 600 mg 每 4 周一次。主要疗效终点是第 16 周掌跖脓疱面积和严重指数 (PPP ASI) 相对于基线的百分比变化。次要终点包括掌跖脓疱医师总体评估 (PPP PGA) 评分为 0/1。评估了安全性（包括不良事件 [AE]、局部耐受性）。

结果

152 名患者接受治疗。未达到主要终点； spesolimab 与安慰剂的平均差异范围为 − 14.6%（95% 置信区间 [CI]：− 31.5%，2.2%）至 − 5.3%（95% CI：− 19.1%，8.6%）；没有一个达到显着性。在第16周时，斯比索利单抗联合安慰剂组中分别有 23 名 (21.1%) 和 2 名 (4.7%) 患者达到 PPP PGA 0/1（平均差异 16.4%；95% CI：3.8%、25.7%），增加至第 52 周时有 59 名（54.1%；联合使用斯佩索利单抗）和 12 名（27.9%；安慰剂改用斯佩索利单抗）患者。与安慰剂相比，非亚洲患者在第 16 周的主要终点（平均差异 − 17.7%；名义P = 0.0394）和 PPP PGA 0/1 方面有显着改善。斯比索利单抗和安慰剂的 AE 和 AE 相关停药率相似。与安慰剂相比，斯培索利单抗的局部耐受性事件和注射部位反应更常见。