Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial.

Yan Zhao; Jianzhong Zhang; Bin Yang; Jingyi LI; Yangfeng Ding; Liming WU; Litao Zhang; Jinyan Wang; Xiaohong Zhu; Furen Zhang; Xiaohua Tao; Yumei LI; Chunlei Zhang; Linfeng LI; Jianyun LU; Qingchun Diao; Qianjin LU; Xiaoyong Man; Fuqiu LI; Xiujuan Xia; Hao Cheng; Yingmin Jia; Guoqing Zhao; Jinchun Yan; Bo Chen

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Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial.

Author: Yan ZHAO ¹ ; Jianzhong ZHANG ¹ ; Bin YANG ² ; Jingyi LI ³ ; Yangfeng DING ⁴ ; Liming WU ⁵ ; Litao ZHANG ⁶ ; Jinyan WANG ⁷ ; Xiaohong ZHU ⁸ ; Furen ZHANG ⁹ ; Xiaohua TAO ¹⁰ ; Yumei LI ¹¹ ; Chunlei ZHANG ¹² ; Linfeng LI ¹³ ; Jianyun LU ¹⁴ ; Qingchun DIAO ¹⁵ ; Qianjin LU ¹⁶ ; Xiaoyong MAN ¹⁷ ; Fuqiu LI ¹⁸ ; Xiujuan XIA ¹⁹ ; Hao CHENG ²⁰ ; Yingmin JIA ²¹ ; Guoqing ZHAO ²¹ ; Jinchun YAN ²¹ ; Bo CHEN ²¹
Author Information

1. Department of Dermatology, Peking University People's Hospital, Beijing 100044, China.
2. Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong 510091, China.
3. Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
4. Department of Dermatology, Shanghai Skin Disease Hospital, Institute of Psoriasis, Tongji University School of Medicine, Shanghai 200443, China.
5. Department of Dermatology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.
6. Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China.
7. Department of Dermatology, Ningbo No.2 Hospital, Ningbo, Zhejiang 315010, China.
8. Department of Dermatology, The Wuxi Second Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu 214002, China.
9. Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Veneorology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250022, China.
10. Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, China.
11. Department of Dermatology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.
12. Department of Dermatology, Peking University Third Hospital, Beijing 100191, China.
13. Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
14. Department of Dermatology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.
15. Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400011, China.
16. Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
17. Department of Dermatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
18. Department of Dermatology, The Second Hospital of Jilin University, Changchun, Jilin 130041, China.
19. Department of Dermatology, Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital, Yantai, Shandong 264000, China.
20. Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.
21. Clinical Department, Keymed Biosciences (Chengdu) Limited, Chengdu, Sichuan 610219, China.
Publication Type:Journal Article
MeSH: Adult; Humans; Dermatitis, Atopic/drug therapy*; Treatment Outcome; Severity of Illness Index; Antibodies, Monoclonal, Humanized/therapeutic use*; Injections, Subcutaneous; Double-Blind Method
From: Chinese Medical Journal 2024;137(2):200-208
CountryChina
Language:English
Abstract: BACKGROUND:Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.
METHODS:This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.
RESULTS:At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.
CONCLUSION:CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.