Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial

Abstract

Background: Atopic dermatitis is a chronic, inflammatory condition causing a substantial burden to patients and caregivers. SHR0302 is an oral, highly selective, Janus kinase 1 inhibitor under investigation for inflammatory skin diseases.

Objective: The aim of this study was to investigate the efficacy and safety of SHR0302 in Chinese patients with moderate to severe atopic dermatitis.

Design and setting: A randomized, double-blind, placebo-controlled, multicenter, phase II trial was conducted in China between October 2019 and August 2020.

Participants: Patients (n = 105) aged 18-75 years with moderate to severe dermatitis and nonresponsive or intolerant to topical or conventional systemic treatments were included.

Interventions: Patients were randomly assigned in a ratio of 1:1:1 to receive SHR0302 4 mg once daily, SHR0302 8 mg once daily, or placebo for 12 weeks.

Main outcome measures: The primary efficacy endpoint was the proportion of patients achieving Investigator's Global Assessment (IGA) response (IGA of 0 [clear] or 1 [almost clear] with improvement of ≥2 grades) at week 12. Secondary efficacy assessments included Eczema Area and Severity Index (EASI) and pruritus Numerical Rating Scale (NRS) scores.

Results: At week 12, IGA response was achieved in nine patients (25.7%; 90% confidence interval [CI] 13.6-37.9%; p = 0.022) in the SHR0302 4 mg group, 19 patients (54.3%; 90% CI 40.4-68.1%; p < 0.001) in the SHR0302 8 mg group, and two patients (5.7%; 90% CI 0.0-12.2%) in the placebo group. EASI75 was achieved in 51.4% (p = 0.013), 74.3% (p < 0.001), and 22.9% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively, while an NRS ≥3-point improvement occurred in 65.7% (p < 0.001), 74.3% (p < 0.001), and 22.9% of patients, respectively. Treatment-emergent adverse events were reported in 60.0%, 68.6%, and 51.4% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively. The adverse events were mild in most cases. Three serious adverse events were reported, all being worsening of atopic dermatitis. No serious infection was reported.

Conclusions and relevance: Oral SHR0302 was effective and well tolerated in Chinese adult patients with moderate to severe atopic dermatitis.

Trial registration: ClinicalTrials.gov identifier: NCT04162899; URL: https://clinicaltrials.gov/ . Date first registered: 14 November 2019.

Conflict of interest statement

Aik Han Goh, Rongjun Liu, and Zhiguo Zhang are employees of Reistone Biopharma Co., Ltd. Yan Zhao, Litao Zhang, Yangfeng Ding, Xiaohua Tao, Chao Ji, Xiuqin Dong, Jianyun Lu, Liming Wu, Rupeng Wang, Qianjin Lu, and Jianzhong Zhang declare they have no conflicts of interest.

© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Figures

Fig. 1

CONSORT diagram. a The primary reason for screening failure was the potential presence of Mycobacterium tuberculosis infection (n = 21). b One patient completed treatment but was lost to follow-up. AD atopic dermatitis, CONSORT Consolidated Standards of Reporting Trials

Fig. 2

Line plots for proportions of patients who achieved a IGA response, b EASI75, and c NRS-3 (FAS). Two subjects in the placebo group had baseline NRS <3, therefore these two subjects would not show an improvement of ≥3 from baseline. The denominator of each treatment group was the number of subjects in the FAS of each treatment group. EASI Eczema Area and Severity Index, FAS full analysis set, IGA Investigator’s Global Assessment, NRS Numerical Rating Scale, W week. *p < 0.05, **p < 0.01, ***p < 0.001