Abstract：
Rationale: Idiopathic pulmonary fibrosis is a fatal and progressive disease with limited treatment options. Objectives: We sought to assess the efficacy and safety of CC-90001, an oral inhibitor of c-Jun N-terminal kinase 1, in patients with idiopathic pulmonary fibrosis. Methods: In a Phase 2, randomized (1:1:1), double-blind, placebo-controlled study (ClinicalTrials.gov ID: NCT03142191), patients received CC-90001 (200 or 400 mg) or placebo once daily for 24 weeks. Background antifibrotic treatment (pirfenidone) was allowed. The primary endpoint was change in the percentage of predicted FVC (ppFVC) from baseline to Week 24; secondary endpoints included safety. Measurements and Main Results: In total, 112 patients received at least one dose of study drug. The study was terminated early because of a strategic decision made by the sponsor. Ninety-one patients (81%) completed the study. The least-squares mean changes from baseline in ppFVC at Week 24 were -3.1% (placebo), -2.1% (200 mg), and -1.0% (400 mg); the differences compared with placebo were 1.1% (200 mg; 95% confidence interval: -2.1, 4.3; P = 0.50) and 2.2% (400 mg; 95% confidence interval: -1.1, 5.4; P = 0.19). Adverse event frequency was similar in patients in the combined CC-90001 arms versus placebo. The most common adverse events were nausea, diarrhea, and vomiting, which were more frequent in patients in CC-90001 arms versus placebo. Fewer patients in the CC-90001 arms than in the placebo arm experienced cough and dyspnea. Conclusions: Treatment with CC-90001 over 24 weeks led to numerical improvements in ppFVC in patients with idiopathic pulmonary fibrosis compared with placebo. CC-90001 was generally well tolerated, which was consistent with previous studies. Clinical trial registered with www.clinicaltrials.gov (NCT03142191).
摘要：
原理：特发性肺纤维化是一种致命的进行性疾病，治疗选择有限。目的：我们试图评估c-JunN末端激酶1口服抑制剂CC-90001在特发性肺纤维化患者中的疗效和安全性。方法：在第二阶段，随机(1：1：1)，双盲,安慰剂对照研究（ClinicalTrials.govID：NCT03142191），患者接受CC-90001(200或400mg)或安慰剂,每日1次,共24周.允许背景抗纤维化治疗(吡非尼酮)。主要终点是预测的FVC（ppFVC）从基线到第24周的百分比变化；次要终点包括安全性。测量和主要结果：总计，112名患者接受了至少一个剂量的研究药物。由于赞助商做出的战略决策，该研究提前终止。91名患者（81%）完成了研究。第24周时ppFVC相对于基线的最小二乘平均变化为-3.1％（安慰剂），-2.1%（200毫克），和-1.0％（400mg）；与安慰剂相比，差异分别为1.1％（200mg；95％置信区间：-2.1，4.3；P=0.50）和2.2％（400mg；95％置信区间：-1.1，5.4；P=0.19）。与安慰剂相比，CC-90001组合组患者的不良事件频率相似。最常见的不良事件是恶心，腹泻,呕吐,与安慰剂相比，CC-90001组患者的频率更高。与安慰剂组相比，CC-90001组中出现咳嗽和呼吸困难的患者更少。结论：与安慰剂相比，CC-90001治疗超过24周导致特发性肺纤维化患者ppFVC的数值改善。CC-90001总体耐受性良好，这与以前的研究一致。在www上注册的临床试验。临床试验。gov（NCT03142191）。
