The British journal of dermatology · 2026
Safety and efficacy of the selective tyrosine kinase 2/Janus kinase 1 inhibitor TLL-018 in patients with moderate-to-severe chronic spontaneous urticaria with inadequate response to H1 antihistamines: a phase Ib, randomized, double-blind, placebo-controlled pilot study.
Клиническое исследование I фазыСтатьяМногоцентровое исследованиеРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Yao Xu, Liu Yi, Luo Yang, Liu Xiaochun, Zhou Min, Yang Bin, Liu Lunfei, Li Linfeng, Liu Weijun, Man Xiaoyong, Chen Aijun, Shi Yuling, Ding Yangfeng, Sun Qing, Tao Juan, Chen Jingjing, Liang Congxin, Lu Qianjin
Аннотация
BACKGROUND: Chronic spontaneous urticaria (CSU) places a considerable burden on both patients and caregivers. Current treatments for CSU are inadequate for some patients. TLL-018, an oral tyrosine kinase 2/Janus kinase 1 (TYK2/JAK1) inhibitor, is currently being investigated as a potential treatment for CSU.
OBJECTIVES: To evaluate the efficacy and safety of TLL-018 for treating moderate-to-severe CSU in patients with an inadequate response to antihistamines.
METHODS: In this multicentre, double-blind, randomized, placebo-controlled, parallel-group pilot study (NCT05373355), patients with CSU who showed an inadequate response to antihistamines were given (1: 1: 1) 10 or 30 mg of TLL-018, or placebo, orally twice daily. After 4 weeks, patients on placebo were switched to TLL-018 20 mg and continued treatment for a further 8 weeks. The primary endpoint was safety, while secondary endpoints included efficacy measures, such as weekly Urticaria Activity Score (UAS7) ≤ 6, UAS7 = 0, and a Dermatology Life Quality Index score of 0 or 1, at weeks 4 and 12.
RESULTS: Overall, 41 patients were randomly assigned to TLL-018 10 mg (n = 14), 30 mg (n = 13) or placebo (n = 14). At week 4, the placebo-adjusted change from baseline (analysed using Ancova) in UAS7, weekly Itch Severity Score and weekly Hive Severity Score was -11.5, -8.0 and -3.8, respectively, in the 10-mg TLL-018 group, and -16.0, -9.0 and -7.0, respectively, in the 30-mg group. At week 12, the proportions of patients achieving UAS7 ≤ 6 and UAS7 = 0 were 54% and 39%, respectively, in the placebo-then-20-mg group, 71% and 64% in the 10-mg group, and 62% and 54% in the 30-mg group. Common treatment-emergent adverse events included elevated serum creatine kinase and blood lipid levels, hyperglycaemia and urinary occult blood.
CONCLUSIONS: TLL-018 was well tolerated and effective in treating moderate-to-severe CSU in patients who had an inadequate response to antihistamines.
OBJECTIVES: To evaluate the efficacy and safety of TLL-018 for treating moderate-to-severe CSU in patients with an inadequate response to antihistamines.
METHODS: In this multicentre, double-blind, randomized, placebo-controlled, parallel-group pilot study (NCT05373355), patients with CSU who showed an inadequate response to antihistamines were given (1: 1: 1) 10 or 30 mg of TLL-018, or placebo, orally twice daily. After 4 weeks, patients on placebo were switched to TLL-018 20 mg and continued treatment for a further 8 weeks. The primary endpoint was safety, while secondary endpoints included efficacy measures, such as weekly Urticaria Activity Score (UAS7) ≤ 6, UAS7 = 0, and a Dermatology Life Quality Index score of 0 or 1, at weeks 4 and 12.
RESULTS: Overall, 41 patients were randomly assigned to TLL-018 10 mg (n = 14), 30 mg (n = 13) or placebo (n = 14). At week 4, the placebo-adjusted change from baseline (analysed using Ancova) in UAS7, weekly Itch Severity Score and weekly Hive Severity Score was -11.5, -8.0 and -3.8, respectively, in the 10-mg TLL-018 group, and -16.0, -9.0 and -7.0, respectively, in the 30-mg group. At week 12, the proportions of patients achieving UAS7 ≤ 6 and UAS7 = 0 were 54% and 39%, respectively, in the placebo-then-20-mg group, 71% and 64% in the 10-mg group, and 62% and 54% in the 30-mg group. Common treatment-emergent adverse events included elevated serum creatine kinase and blood lipid levels, hyperglycaemia and urinary occult blood.
CONCLUSIONS: TLL-018 was well tolerated and effective in treating moderate-to-severe CSU in patients who had an inadequate response to antihistamines.