Clinical Trial Readiness - Primary Ciliary Dyskinesia (CTR-PCD)

项目摘要 在本建议书中，我们将确定可行性、可靠性、分析影响和优化 移动的健康呼吸终点测量的质量，用于计划的III期临床试验， 原发性纤毛运动障碍（PCD）患者。这些结果将适用于越来越多的临床 计划在PCD中进行的试验以及在其他慢性肺部疾病中进行的试验和临床护理环境。PCD是一种罕见的 粘膜纤毛清除障碍导致呼吸道慢性细菌感染的遗传病 导致进行性气道损伤和反复呼吸道恶化（RTEs）。 COVID大流行加速了临床试验设计的范式转变， 患者通过远程端点确认。作为罕见疾病人群的成员，PCD患者通常 远离研究中心，增加了参与临床试验的障碍。远程端点监控 可以改善罕见疾病人群的临床试验。此外， 可以远程测量的终点有可能减少样本量要求， 用于测量特发性肺纤维化患者的肺功能。 Parion Sciences最近发现了他们的新型吸入性上皮钠的1期试验的有希望的结果 在PCD患者中使用ENaC通道抑制剂，目前正在计划一项3期随机对照试验。的 拟定的主要和次要终点是一秒用力呼气量（FEV 1）和 RTE。Parion有兴趣将这些终点的家庭测量纳入试验。然而，首先， 关于家庭终点测量的可行性和临床有效性的重要知识差距必须 被解决。 我们建议对现有的NIH罕见病临床研究网络纵向进行辅助研究， 在PCD儿童和成人队列中进行的RTE观察性研究。40名参与者将参加6 个月他们将进行家庭肺功能测定，并完成一个简单的6项电子患者报告结果 周刊本研究的目的是评估每周家庭肺功能测定和RTE的可行性和有效性 检测，以告知将这些终点纳入Parion Sciences计划的3期临床试验。的 目的是：1）评估每周进行家庭肺功能测定的可行性，可靠性和分析影响， 6个月; 2）比较两种不同的已发表的RTE定义的分析影响， ePRO每周给药一次，持续6个月，3）描述肺功能和RTE之间的相关性 远程确认。

Project Summary In this proposal, we will establish the feasibility, reliability, analytic impact and conditions that optimize the quality of mobile health respiratory endpoint measurements for use in a planned Phase 3 clinical trial in patients with primary ciliary dyskinesia (PCD). The results will be applicable to the growing number of clinical trials planned in PCD as well as trials in other chronic lung diseases and to clinical care settings. PCD is a rare genetic disease in which impaired mucociliary clearance leads to chronic bacterial infections of the respiratory tract resulting in progressive airway damage and recurrent respiratory tract exacerbations (RTEs). The COVID pandemic has accelerated a paradigm shift in clinical trial design that “brings the trial to the patient” through remote endpoint ascertainment. As members of a rare disease population, PCD patients often live far from research centers, increasing barriers to clinical trial participation. Remote endpoint monitoring could improve access to clinical trials for rare disease populations. Furthermore, the greater frequency with which endpoints can be measured remotely has the potential to decrease sample size requirements, as has been shown for measurement of lung function in idiopathic pulmonary fibrosis. Parion Sciences recently found promising results of a Phase 1 trial of their novel inhaled epithelial sodium channel (ENaC) inhibitor in PCD patients and is now planning a Phase 3 randomized controlled trial. The proposed primary and secondary endpoints are the forced expiratory volume in one second (FEV1) and rate of RTEs. Parion is interested in incorporating home measurement of these endpoints into the trial. First, however, important knowledge gaps regarding the feasibility and clinical validity of home endpoint measurements must be addressed. We propose an ancillary study to an existing NIH Rare Disease Clinical Research Network longitudinal, observational study of RTEs in a cohort of children and adults with PCD. Forty participants will be enrolled for 6 months. They will perform home spirometry and complete a simple 6-item electronic patient reported outcome weekly. The objective of the study is to evaluate the feasibility and validity of weekly home spirometry and RTE detection to inform incorporation of these endpoints into Parion Sciences’ planned Phase 3 clinical trial. The aims are: 1) To evaluate the feasibility, reliability and analytic impact of home spirometry performed weekly for 6 months; 2) To compare the analytic impact of two different published definitions of an RTE as detected using an ePRO administered weekly for 6 months, 3) To describe the associations between lung function and RTEs ascertained remotely.