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.

backgroundAtopic 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.

objectiveThe aim of this study was to investigate the efficacy and safety of SHR0302 in Chinese patients with moderate to severe atopic dermatitis. DESIGN AND

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

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

interventionsPatients 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 measuresThe 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.

resultsAt 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 registrationClinicalTrials.gov identifier: NCT04162899; URL: https://clinicaltrials.gov/ . Date first registered: 14 November 2019.