1 Clinical Development.
2 Department of General Respiratory Medicine and Lung Transplantation, The Alfred Hospital, Melbourne, Australia.
Am J Respir Crit Care Med. 2018 Jan 1;197(1):94-103. doi: 10.1164/rccm.201704-0784OC.
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.
Investigate efficacy and safety of tralokinumab, a human anti-IL-13 monoclonal antibody, in subjects with mild to moderate IPF.
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 FVC in the intention-to-treat population. Exploratory analyses included assessment of clinical response in subgroups with baseline serum periostin concentration above/below median.
The study was stopped due to lack of efficacy after interim analysis. Neither tralokinumab 400 mg nor tralokinumab 800 mg met the primary endpoint; least-squares mean difference (95% confidence interval) percent predicted FVC from baseline to Week 52: -1.77 (-4.13 to 0.59) (P = 0.140) and -1.41 (-3.73 to 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 greater than or equal to 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, tralokinumab 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.
Tralokinumab demonstrated an acceptable safety and tolerability profile but did not achieve key efficacy endpoints. Clinical trial registered with www.clinicaltrials.gov (NCT01629667).
白细胞介素 13（IL-13）是特发性肺纤维化（IPF）的潜在治疗靶点；临床前数据表明其在组织纤维化中发挥作用，在疾病进展迅速的患者中表达增加。
研究抗白细胞介素 13 单克隆抗体特拉洛单抗（tralokinumab）治疗轻中度 IPF 患者的疗效和安全性。
将受试者按 1:1:1 的比例随机分配，分别接受特拉洛单抗（400 或 800 mg）、安慰剂静脉输注，每 4 周 1 次，共 68 周。主要终点为意向治疗人群从基线到第 52 周时用力肺活量预计值的百分比变化。探索性分析包括评估基线时血清骨膜蛋白浓度高于/低于中位数的亚组的临床反应。
中期分析后因缺乏疗效而停止研究。特拉洛单抗 400 mg 或 800 mg 均未达到主要终点；从基线到第 52 周的用力肺活量预计值的最小二乘均数差异（95%置信区间）：-1.77（-4.13 至 0.59）（P=0.140）和-1.41（-3.73 至 0.91）（P=0.234）。按基线骨膜蛋白浓度定义的亚组中，两个治疗组的主要终点也未达到。特拉洛单抗治疗组在第 52 周时用力肺活量预计值下降大于或等于 10%的患者比例高于安慰剂组。特拉洛单抗 400 mg、800 mg 和安慰剂的最常见治疗相关不良事件分别为咳嗽（17.5%、30.5%、22.8%）、IPF 进展和加重（21.1%、16.9%、22.8%）和上呼吸道感染（17.5%、20.3%、12.3%）。
特拉洛单抗具有可接受的安全性和耐受性，但未达到主要疗效终点。临床试验已在 www.clinicaltrials.gov 注册（NCT01629667）。
