Efficacy And Safety Study Of The JAK1 Inhibitor SHR0302 In Adult Patients With Moderate To Severe Atopic Dermatitis

Objective: To evaluate the efficacy and safety of oral administration of SHR03024 mg once a day(QD)and SHR0302 8mg(QD)in adult subjects with moderate to severe Atopic dermatitis(AD).Methods: A randomized,double-blind,placebo-controlled,parallel multicenter clinical study was carried out,including a 4-week screening period,a 12-week blind method treatment period and a 2-week follow-up period after the last administration.18 adult subjects with moderate to severe AD who met the inclusion criteria were randomly assigned to three study groups: 4mg QD group(n = 6),8mg QD group(n =6)or placebo group(n = 6)according to the ratio of 1:1:1,and received blind method treatment for 12 weeks.The primary efficacy index(Percentage of subjects who achieved Ig A response at 12 weeks)and the secondary efficacy index[Percentage of change of EASI score compared with baseline at the 12 th week;Percentage of subjects with EASI score improvement ? 50%,75% and 90% compared with baseline at week 12(EASI50?EASI75?EASI90);Percentage of changes in the atopic dermatitis score(SCORAD)compared with baseline at week 12;Percentage of subjects with SCORAD improvement ? 50%,75%,90% compared with baseline at week 12(SCORAD50 ? SCORAD75 ? SCORAD90);Percentage of change in numerical rating scale(NRS)compared with baseline at week 12;Percentage of subjects with NRS improvement ? 3(NRS-3)at week 12 compared with baseline]were statistically analyzed.Meanwhile,the adverse events of the three groups were statistically analyzed.Results:A total of 18 patients were enrolled in the study,including 6 patients in placebo group,4mg QD group and 8mg QD group,respectively.Primary efficacy index:The proportion of subjects who received 4mg QD and 8mg QD SHR0302 treatment with IGA response at the 12 th week was higher than that of the placebo group,the difference was statistically significant(all P<0.05).Among them,the proportion of subjects who received 8mg SHR0302 tablets achieving the primary endpoint was higher than that of 4mg(83.3%,16.7%).Secondary efficacy index:The improvement of EASI compared with baseline in the 4mg and 8mg dose groups at 12 week was significant(53.57%,65.87),and the differences were statistically significant(all P values <0.05).At the 12 th week,the percentage of people who reached EASI50,EASI75 and EASI90 in 4mg QD and 8mg QD SHR0302 group were significantly higher than those in placebo group(33.3%/16.7%/16.7%,50%/33.3%/33.3% vs 0%).The improvement of SCORAD from baseline in the 4mg and 8mg dose groups at 12 week was significant(55.81%,67.12%),and the differences were statistically significant compared with the placebo group(all P values <0.05);At the 12 th week,the percentage of people who reached SCORAD50/75 in 4mg and 8mg groups were significantly higher than those in placebo group(83.3%/33.3%,100%/50% vs 0%);The NRS of pruritus in 4mg and 8mg dose groups at 12 week had significantl improvement(51.09%,73.92%),and the differences were statistically significant(all P<0.05).Compared with the placebo group,the percentage of NRS-3 in the 4 mg and8 mg dose groups were significantly higher(100%,100% vs 0%).Safety and adverse events: There were no serious adverse events in 4 mg QD,8 mg QD SHR0302 group and placebo group.Only 1 patient showed a slight increase in transient liver function,which was in the 8mg dose group,which may be related to the study drug.The dosage of the study drug was not changed,and the patient did not develop to SAE.Conclusions: Oral administration of 4 mg and 8 mg SHR0302 tablets(QD)for 12 weeks can improve the clinical symptoms and quality of life of adult subjects with moderate to severe AD;The research results are consistent with the drug properties of SHR0302 as a highly selective JAK1 inhibitor.The data of this study show that SHR0302 has the potential of effective and safe treatment for subjects with AD.