The British journal of dermatology · 2025
An open-label randomized parallel-group phase I study of the oral Bruton tyrosine kinase inhibitor tirabrutinib in systemic sclerosis.
Клиническое исследование I фазыСтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Matsuda Kazuki M, Harada Tomohiro, Doi Masaaki, Io Toshiro, Kitani Akihiro, Hasegawa Minoru, Sato Shinichi, Yoshizaki Ayumi
Аннотация
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune connective tissue disease with a high risk of organ damage and mortality.
OBJECTIVES: To investigate whether tirabrutinib, an inhibitor of Bruton tyrosine kinase, is useful for treating SSc.
METHODS: This randomized double-arm 52-week phase I study investigated the safety, efficacy and putative mechanism of action of once--daily tirabrutinib in adults with SSc (Japan Registry of Clinical Trials jRCT2031200315). The primary endpoints were safety, including treatment-emergent adverse events (TEAEs), and pharmacokinetics. Exploratory efficacy endpoints included the modified Rodnan skin score (mRSS) and mechanism of action determined via immunophenotyping and RNA sequencing (RNAseq).
RESULTS: Sixteen patients were enrolled and treated with 40 mg or 80 mg tirabrutinib (n = 8 per group). All 16 patients experienced grade 1 or 2 TEAEs. Plasma tirabrutinib concentrations in steady-state conditions were within the expected ranges. The mean (SD) change in mRSS from baseline to week 52 was -4.0 (6.1) and -4.7 (3.6) in the 40-mg and 80-mg groups, respectively. The percentage of naïve B cells tended to increase, and the percentages of nonswitched memory B cells, activated memory CD95+ B cells, and plasmablasts tended to decrease in both groups. Immunophenotyping and RNAseq suggested that suppression of B-cell activity was involved in the mechanism of action of tirabrutinib.
CONCLUSIONS: This study suggests that tirabrutinib is tolerable in patients with SSc and acts by suppressing B-cell activity.
OBJECTIVES: To investigate whether tirabrutinib, an inhibitor of Bruton tyrosine kinase, is useful for treating SSc.
METHODS: This randomized double-arm 52-week phase I study investigated the safety, efficacy and putative mechanism of action of once--daily tirabrutinib in adults with SSc (Japan Registry of Clinical Trials jRCT2031200315). The primary endpoints were safety, including treatment-emergent adverse events (TEAEs), and pharmacokinetics. Exploratory efficacy endpoints included the modified Rodnan skin score (mRSS) and mechanism of action determined via immunophenotyping and RNA sequencing (RNAseq).
RESULTS: Sixteen patients were enrolled and treated with 40 mg or 80 mg tirabrutinib (n = 8 per group). All 16 patients experienced grade 1 or 2 TEAEs. Plasma tirabrutinib concentrations in steady-state conditions were within the expected ranges. The mean (SD) change in mRSS from baseline to week 52 was -4.0 (6.1) and -4.7 (3.6) in the 40-mg and 80-mg groups, respectively. The percentage of naïve B cells tended to increase, and the percentages of nonswitched memory B cells, activated memory CD95+ B cells, and plasmablasts tended to decrease in both groups. Immunophenotyping and RNAseq suggested that suppression of B-cell activity was involved in the mechanism of action of tirabrutinib.
CONCLUSIONS: This study suggests that tirabrutinib is tolerable in patients with SSc and acts by suppressing B-cell activity.