一个Seladelpar的第3期试验在初级胆道胆管炎中
Gideon M Hirschfield1, Christopher L Bowlus1, Marlyn J Mayo1
1From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital.
塞拉德尔帕显著改善了原发性胆道胆炎患者的生化反应,并使性酸酶水平正常化. 这种治疗也有效地减少了中度至严重的患者的.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 临床试验 临床试验
- 药理学 药理学是指药理学的学科.
背景情况:
- 初级胆道胆炎 (PBC) 的有效治疗选择有限.
- 塞拉德尔帕是一种氧酶增殖器激活的受体三角体激动剂,在PBC治疗中表现有前途.
研究的目的:
- 评估seladelpar在PBC患者中的疗效和安全性.
- 评估seladelpar对生物化学标志物和的影响.
主要方法:
- 一个为期12个月的双盲,安慰剂控制的第三阶段试验.
- 193名对ursodeoxycholic酸反应不充分或不耐受的患者被随机分配 (2:1) 接受口服seladelpar (每天10毫克) 或安慰剂.
- 主要终点:生化反应 (性酸酶<1.67 ULN,≥15%降低,正常 bilirubin). 二级终点包括性酸酶的正常化和的减少.
主要成果:
- 61.7%的塞拉德拉帕患者实现了生物化学反应,而安慰剂为20.0% (P<0.001).
- 性酸酶的正常化发生在25.0%的seladelpar患者和0%的安慰剂 (P<0.001) 中.
- 在中度至重症病例中,塞拉德尔帕显著降低了的得分 (平均差异-1.5,P=0.005).
结论:
- 塞拉德尔帕在改善生化标志物和减少PBC患者的方面表现出显著的有效性.
- 在seladelpar和安慰剂组之间,不良事件发生率和严重程度相似.
- 塞拉德尔帕代表了对一次性胆道胆道炎的潜在新疗法选择.
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