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A Phase 2 Randomized Controlled Study of Tralokinumab in Subjects with Idiopathic Pulmonary Fibrosis
American Journal of Respiratory and Critical Care Medicine ( IF 24.7 ) Pub Date : 2017-08-08 , DOI: 10.1164/rccm.201704-0784oc
Joseph M. Parker 1 , Ian N. Glaspole 2, 3 , Lisa H. Lancaster 4 , Tarik J. Haddad 5 , Dewei She 6 , Stephanie L. Roseti 1 , Jon P. Fiening 7 , Ethan P. Grant 8 , Chris M. Kell 9 , Kevin R. Flaherty 10
Affiliation  

Rationale: Interleukin (IL)-13 is a potential therapeutic target for idiopathic pulmonary fibrosis (IPF); preclinical data suggest a role in tissue fibrosis, and expression is increased in subjects with rapidly progressing disease. Objectives: Investigate efficacy and safety of tralokinumab, a human anti–IL-13 monoclonal antibody, in subjects with mild to moderate IPF. Methods: Subjects received tralokinumab (400 or 800 mg), or placebo, intravenously every 4 weeks for 68 weeks. The primary endpoint was change from baseline to Week 52 in percent-predicted forced vital capacity (FVC) in the intention to-treat population. Exploratory analyses included assessment of clinical response in subgroups with baseline serum periostin concentration above/below median. Measurements and Main Results: The study was stopped due to lack of efficacy after interim analysis. Neither tralokinumab 400 mg nor 800 mg met the primary endpoint; least-squares mean difference [95% CI] percent-predicted FVC from baseline to Week 52: –1.77 [–4.13, 0.59] (P = 0.140) and –1.41 [–3.73, 0.91] (P = 0.234), respectively. The primary endpoint was also not met in either treatment group in subgroups defined by periostin baseline concentration. The percentage of subjects with decline in percent-predicted FVC ≥10% at Week 52 was numerically greater for tralokinumab-treated subjects, compared with placebo. The most common treatment-emergent adverse events for tralokinumab 400 mg, 800 mg, and placebo were cough (17.5%, 30.5%, 22.8%), IPF progression and exacerbation (21.1%, 16.9%, 22.8%), and upper respiratory tract infection (17.5%, 20.3%, 12.3%), respectively. Conclusions: Tralokinumab demonstrated an acceptable safety and tolerability profile but did not achieve key efficacy endpoints. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01629667.

中文翻译:

Tralokinumab在特发性肺纤维化患者中的2期随机对照研究

理由:白介素(IL)-13是特发性肺纤维化(IPF)的潜在治疗靶点;临床前数据表明在组织纤维化中起作用,并且在疾病快速发展的受试者中表达增加。目的:研究轻度至中度IPF患者抗人IL-13单克隆抗体tralokinumab的疗效和安全性。方法:受试者每4周静脉接受tralokinumab(400或800 mg)或安慰剂,共68周。主要终点是从基线到第52周的意图治疗人群中预测百分比的强制肺活量(FVC)的变化。探索性分析包括评估基线血清骨膜素浓度高于中位数/低于中位数的亚组的临床反应。测量和主要结果:中期分析后,由于缺乏疗效而终止了该研究。曲妥珠单抗400 mg和800 mg均未达到主要终点;从基线到第52周的最小平方均方差[95%CI]预测的FVC:分别为–1.77 [–4.13,0.59](P = 0.140)和–1.41 [–3.73,0.91](P = 0.234)。骨膜素基线浓度所定义的亚组中,任一治疗组的主要终点均未达到。与安慰剂相比,经曲妥珠单抗治疗的受试者在52周时FVC百分率预测≥10%下降的受试者百分比在数值上更大。曲妥珠单抗400 mg,800 mg和安慰剂最常见的治疗紧急事件是咳嗽(17.5%,30.5%,22.8%),IPF恶化和恶化(21.1%,16.9%,22.8%)和上呼吸道感染(分别为17.5%,20.3%,12.3%)。结论:曲洛单抗显示出可接受的安全性和耐受性,但未达到关键的疗效终点。可以在www.clinicaltrials.gov上获取临床试验注册信息,ID NCT01629667。
更新日期:2017-09-05
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