دورية أكاديمية
Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials.
| العنوان: | Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials. |
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| المؤلفون: | Harrison, Stephen A, Wong, Vincent Wai-Sun, Okanoue, Takeshi, Bzowej, Natalie, Vuppalanchi, Raj, Younes, Ziad, Kohli, Anita, Sarin, Shiv, Caldwell, Stephen H, Alkhouri, Naim, Shiffman, Mitchell L, Camargo, Marianne, Li, Georgia, Kersey, Kathryn, Jia, Catherine, Zhu, Yanni, Djedjos, C Stephen, Subramanian, G Mani, Myers, Robert P, Gunn, Nadege, Sheikh, Aasim, Anstee, Quentin M, Romero-Gomez, Manuel, Trauner, Michael, Goodman, Zachary, Lawitz, Eric J, Younossi, Zobair, Peyton, Adam, DO |
| المصدر: | Department of Medicine |
| بيانات النشر: | LVHN Scholarly Works |
| سنة النشر: | 2020 |
| المجموعة: | Lehigh Valley Health Network: LVHN Scholarly Works |
| مصطلحات موضوعية: | Benzamides, Biopsy, Disease Progression, Dose-Response Relationship, Drug, Double-Blind Method, Drug Monitoring, Female, Humans, Imidazoles, Liver, Liver Cirrhosis, MAP Kinase Kinase Kinase 5, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, Protein Kinase Inhibitors, Pyridines, Treatment Outcome, Department of Medicine, Medicine and Health Sciences |
| الوصف: | BACKGROUND & AIMS: Apoptosis signal-regulating kinase 1 (ASK1) plays a key role in hepatocyte injury, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH). We evaluated the safety and antifibrotic effect of selonsertib, a selective inhibitor of ASK1, in patients with advanced fibrosis due to NASH. METHODS: We conducted 2 randomized, double-blind, placebo-controlled, phase III trials of selonsertib in patients with NASH and bridging fibrosis (F3, STELLAR-3) or compensated cirrhosis (F4, STELLAR-4). Patients were randomized 2:2:1 to receive selonsertib 18 mg, selonsertib 6 mg, or placebo once daily for 48 weeks. Liver biopsies were performed at screening and week 48 and non-invasive tests of fibrosis (NITs) were evaluated. The primary efficacy endpoint was the proportion of patients with ≥1-stage improvement in fibrosis without worsening of NASH at week 48. Additional endpoints included changes in NITs, progression to cirrhosis (in STELLAR-3), and liver-related clinical events. RESULTS: Neither trial met the primary efficacy endpoint. In STELLAR-3, fibrosis improvement without worsening of NASH was observed in 10% (31/322, p = 0.49 vs. placebo), 12% (39/321, p = 0.93 vs. placebo), and 13% (21/159) of patients in the selonsertib 18 mg, selonsertib 6 mg, and placebo groups, respectively. In STELLAR-4, the primary endpoint was achieved in 14% (51/354; p = 0.56), 13% (45/351; p = 0.93), and 13% (22/172) of patients, respectively. Although selonsertib led to dose-dependent reductions in hepatic phospho-p38 expression indicative of pharmacodynamic activity, it had no significant effect on liver biochemistry, NITs, progression to cirrhosis, or adjudicated clinical events. The rates and types of adverse events were similar among selonsertib and placebo groups. CONCLUSIONS: Forty-eight weeks of selonsertib monotherapy had no antifibrotic effect in patients with bridging fibrosis or compensated cirrhosis due to NASH. LAY SUMMARY: Patients with non-alcoholic steatohepatitis (NASH) can develop scarring of ... |
| نوع الوثيقة: | text |
| اللغة: | unknown |
| العلاقة: | https://scholarlyworks.lvhn.org/medicine/6750Test; https://pubmed.ncbi.nlm.nih.gov/32147362Test/ |
| الإتاحة: | https://scholarlyworks.lvhn.org/medicine/6750Test https://pubmed.ncbi.nlm.nih.gov/32147362Test/ |
| رقم الانضمام: | edsbas.1E1EA87B |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |