Efficacy and Safety of GR1802 in Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial

IF 3.4 4区医学 Q1 DERMATOLOGY

Dermatologic Therapy Pub Date : 2025-03-12 DOI:10.1155/dth/6903760

Shangshang Wang, Litao Zhang, Yunsheng Liang, Shifa Zhang, Jingyan Wang, Xiaoyong Man, Chao Ji, Rixin Chen, Guang Xiang, Zudong Meng, Chunjun Yang, Hao Cheng, Qi Wang, Lin-feng Li, Siping Zhang, Yanfeng Ding, Quangang Zhu, Lanying Qin, Yumei Li, Qianjin Lu, Li Xia, Shuanglin Cao, Chunshui Yu, Xinsuo Duan, Liming Wu, Chunlei Zhang, Congjun Jiang, Wei Wang, Jinhua Xu

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Abstract

Background: GR1802 is a newly developed, fully humanized monoclonal antibody targeting the interleukin-4 receptor alpha (IL-4Rα) subunit, which is a component common to both the IL-4 and IL-13 receptor complexes.

Objectives: Our objective was to assess the efficacy of GR1802 in adult patients presenting with moderate-to-severe atopic dermatitis.

Methods: In this clinical trial, patients with moderate-to-severe atopic dermatitis were randomly assigned to receive either 300 mg GR1802, 150 mg GR1802, or a placebo every 2 weeks for 16 weeks. Primary endpoints were the Eczema Area and Severity Index (EASI-75) response rates at Week 16. Secondary efficacy outcomes included responders at various evaluation points from baseline to study end: IGA 0/1 with ≥ 2-point improvement; EASI-75, EASI-90, and EASI-50; and ≥ 3- or ≥ 4-point improvements in weekly average daily PP-NRS score. Safety was evaluated throughout the study.

Results: From August 2022 to February 2023, 120 patients were randomized to receive either GR1802 150 mg (n = 40), GR1802 300 mg (n = 40), or placebo (n = 40), with 107 completing the study. GR1802 demonstrated a higher proportion of patients achieving EASI-75 at Week 16 compared with the placebo group, and the observed differences in EASI-75 response rates were 39.1% (GR1802 300 mg vs. placebo, 95% CI 20.0–58.2, p = 0.0002) and 19.4% (GR1802 150 mg vs. placebo, 95% CI −0.8–39.7, p = 0.0740). The GR1802 300 mg group also showed greater efficacy on secondary endpoints compared to the GR1802 150 mg group. Serious adverse events occurred in 10% of placebo patients, 2.5% of the GR1802 150 mg group, and none in the GR1802 300 mg group. Treatment-emergent AEs occurred in 75.0% of the GR1802 150 mg group, 82.5% of the GR1802 300 mg group, and 85.0% of the placebo group.

Conclusions: GR1802 was well tolerated and effective in moderate-to-severe AD patients, showing a dose–response trend at 150–300 mg.

Trial Registration: Chinese Registry of Clinical Trials: ChiCTR2100051917

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GR1802治疗中重度特应性皮炎的疗效和安全性：一项多中心、随机、双盲、安慰剂对照的2期临床试验

背景：GR1802是一种新开发的完全人源化的靶向IL-4受体α (IL-4Rα)亚基的单克隆抗体，该亚基是IL-4和IL-13受体复合物的共同成分。目的：我们的目的是评估GR1802对中重度特应性皮炎成人患者的疗效。方法：在这项临床试验中，中重度特应性皮炎患者被随机分配每2周接受300 mg GR1802、150 mg GR1802或安慰剂治疗，持续16周。主要终点是第16周时湿疹面积和严重程度指数（EASI-75）的缓解率。次要疗效结果包括从基线到研究结束各评价点的应答者：IGA 0/1，改善≥2点；EASI-75、EASI-90和EASI-50；每周平均每日PP-NRS评分改善≥3或≥4分。在整个研究过程中对安全性进行了评估。结果：从2022年8月到2023年2月，120名患者随机接受GR1802 150 mg （n = 40）、GR1802 300 mg （n = 40）或安慰剂（n = 40）， 107名患者完成了研究。与安慰剂组相比，GR1802在第16周达到EASI-75的患者比例更高，观察到的EASI-75缓解率差异为39.1% （GR1802 300 mg vs安慰剂，95% CI 20.0-58.2, p = 0.0002）和19.4% （GR1802 150 mg vs安慰剂，95% CI - 0.8-39.7, p = 0.0740）。与GR1802 150 mg组相比，GR1802 300 mg组在次要终点上也显示出更高的疗效。10%的安慰剂患者发生严重不良事件，GR1802 150 mg组为2.5%，GR1802 300 mg组无严重不良事件。GR1802 150 mg组出现治疗性不良事件的比例为75.0%，GR1802 300 mg组为82.5%，安慰剂组为85.0%。结论：GR1802在中重度AD患者中具有良好的耐受性和有效性，在150 ~ 300 mg范围内呈剂量-反应趋势。试验注册：中国临床试验注册中心：ChiCTR2100051917

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来源期刊

Dermatologic Therapy 医学-皮肤病学

CiteScore

7.00

自引率

8.30%

发文量

711

审稿时长

3 months

期刊介绍： Dermatologic Therapy has been created to fill an important void in the dermatologic literature: the lack of a readily available source of up-to-date information on the treatment of specific cutaneous diseases and the practical application of specific treatment modalities. Each issue of the journal consists of a series of scholarly review articles written by leaders in dermatology in which they describe, in very specific terms, how they treat particular cutaneous diseases and how they use specific therapeutic agents. The information contained in each issue is so practical and detailed that the reader should be able to directly apply various treatment approaches to daily clinical situations. Because of the specific and practical nature of this publication, Dermatologic Therapy not only serves as a readily available resource for the day-to-day treatment of patients, but also as an evolving therapeutic textbook for the treatment of dermatologic diseases.