CC-90001, a c-Jun N-terminal kinase (JNK) inhibitor, in patients with pulmonary fibrosis: design of a phase 2, randomised, placebo-controlled trial.
CC-90001, a c-Jun N-terminal kinase (JNK) inhibitor, in patients with pulmonary fibrosis: design of a phase 2, randomised, placebo-controlled trial.
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DOI：
10.1136/bmjresp-2021-001060
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发表时间：
2022-01
影响因子：
4.1
通讯作者：
Greenberg S
中科院分区：
文献类型：
--
作者：
Popmihajlov Z;Sutherland DJ;Horan GS;Ghosh A;Lynch DA;Noble PW;Richeldi L;Reiss TF;Greenberg S
特发性肺纤维化(IPF)是一种进行性间质性肺疾病(ILD)，通常是致命的；其他间质性肺间质疾病(ILD)具有进行性纤维化表型(PF-ILD)。抗纤维化药物可以减缓但不能阻止IPF或PF-ILD患者的疾病进展。C-jun氨基末端激酶(JNKs)是一种应激激活的蛋白激酶，参与了纤维化的潜在机制，包括上皮细胞死亡、纤维化前巨噬细胞的炎症和极化、成纤维细胞的激活和胶原的产生。CC-90001是一种口服(PO)，每天一次，JNK抑制剂，正在接受IPF和PF-ILD的评估。这是一项第2阶段的随机、双盲、安慰剂对照研究，评估CC-90001在特发性肺间质纤维化患者(主研究)和肺间质纤维化患者(子研究)中的有效性和安全性。两者都包括8周的筛查期，24周的治疗期，最多80周的积极治疗延期和4周的治疗后随访。患有特发性肺纤维化的患者将以1：1：1的随机比例接受200mgCC-90001或400 mgCC-90001或安慰剂口服，每天一次；最多25名患者/组将被允许与吡非尼酮同时使用。在PF-ILD亚研究中，45名患者将以2：1的随机比例接受400mgCC-90001或安慰剂治疗。主要终点是IPF患者从基线到第24周的预测用力肺活量百分比的变化。这项研究将按照良好临床实践指南、赫尔辛基原则宣言以及当地的道德和法律要求进行。结果将在同行评议的出版物中公布。NCT03142191。
Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal interstitial lung disease (ILD); other ILDs have a progressive, fibrotic phenotype (PF-ILD). Antifibrotic agents can slow but not stop disease progression in patients with IPF or PF-ILD. c-Jun N-terminal kinases (JNKs) are stress-activated protein kinases implicated in the underlying mechanisms of fibrosis, including epithelial cell death, inflammation and polarisation of profibrotic macrophages, fibroblast activation and collagen production. CC-90001, an orally administered (PO), one time per day, JNK inhibitor, is being evaluated in IPF and PF-ILD. This is a phase 2, randomised, double-blind, placebo-controlled study evaluating efficacy and safety of CC-90001 in patients with IPF (main study) and patients with PF-ILD (substudy). Both include an 8-week screening period, a 24-week treatment period, up to an 80-week active-treatment extension and a 4-week post-treatment follow-up. Patients with IPF (n=165) will be randomised 1:1:1 to receive 200 mg or 400 mg CC-90001 or placebo administered PO one time per day; up to 25 patients/arm will be permitted concomitant pirfenidone use. Forty-five patients in the PF-ILD substudy will be randomised 2:1 to receive 400 mg CC-90001 or placebo. The primary endpoint is change in per cent predicted forced vital capacity from baseline to Week 24 in patients with IPF. This study will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles and local ethical and legal requirements. Results will be reported in a peer-reviewed publication. NCT03142191.
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影响因子：
6.9
作者：
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通讯作者：
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影响因子：
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Molina-Molina M
DOI：
10.1165/rcmb.2008-0174oc
发表时间：
2009-04-01
影响因子：
6.4
作者：
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通讯作者：
Janssen-Heininger, Yvonne M. W.
影响因子：
168.9
作者：
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通讯作者：
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