Spagnolo Paolo, Maher Toby M
Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
Department of Pulmonary, Critical Care and Sleep Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
Curr Opin Pulm Med. 2024 Sep 1;30(5):494-499. doi: 10.1097/MCP.0000000000001099. Epub 2024 Jul 4.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis and limited therapeutic options. A multitude of promising compounds are currently being investigated; however, the design and conductance of late-phase clinical trials in IPF has proven particularly challenging.
Despite promising phase 2 data, ziritaxestat, an autotaxin inhibitor, pentraxin-2, an endogenous protein that regulates wound healing and fibrosis, and pamrevlumab, a human monoclonal antibody against connective tissue growth factor, failed to show efficacy in phase 3 trials. Endpoint selection is critical for the design, execution, and success of clinical trials; recently, attention has been paid to the assessment of how patients feel, function, and survive with the aim of aligning scientific objectives and patient needs in IPF. External control arms are control patients that derive from historical randomized controlled trials, registries, or electronic health records. They are increasingly used to assess treatment efficacy in clinical trials owing to their potential to reduce study duration and cost and increase generalizability of findings.
Advances in study design, end point selection and statistical analysis, and innovative strategies for more efficient enrolment of study participants have the potential to increase the likelihood of success of late-phase clinical trials in IPF.
特发性肺纤维化（IPF）是一种预后不良且治疗选择有限的进行性肺部疾病。目前正在研究多种有前景的化合物；然而，IPF晚期临床试验的设计和实施已证明极具挑战性。
尽管2期数据很有前景，但自分泌运动因子抑制剂齐瑞他司他、调节伤口愈合和纤维化的内源性蛋白质五聚素-2以及抗结缔组织生长因子人单克隆抗体帕姆瑞单抗在3期试验中均未显示出疗效。终点选择对于临床试验的设计、实施和成功至关重要；最近，人们关注评估患者的感受、功能和生存情况，旨在使IPF的科学目标与患者需求保持一致。外部对照臂是来自历史随机对照试验、登记处或电子健康记录的对照患者。由于它们有可能缩短研究持续时间和成本并提高研究结果的普遍性，因此越来越多地用于评估临床试验中的治疗效果。
研究设计、终点选择和统计分析方面的进展，以及更有效地招募研究参与者的创新策略，有可能增加IPF晚期临床试验成功的可能性。
