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

临床试验准备 - 原发性纤毛运动障碍 (CTR-PCD)

• 批准号: 10656216
• 负责人: Margaret Rosenfeld
• 金额: $ 16.94万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656216
• 关键词: Acceleration; Acute; Address; Adherence; Adult; Age; Agreement; American; Ancillary Study; Bacterial Infections; COVID-19 pandemic; Characteristics; Chest; Child; Chronic; Chronic lung disease; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Conduct Clinical Trials; Detection; Diagnosis; Disease; Duchenne muscular dystrophy; Enrollment; Feasibility Studies; Forced expiratory volume function; Frequencies; Future; Genetic; Genetic Diseases; Home; Impairment; Improve Access; Inhalation; Knowledge; Linear Regressions; Longitudinal Studies; Longitudinal, observational study; Lower respiratory tract structure; Measurement; Measures; Methods; Modeling; Monitor; Mucociliary Clearance; Natural History; Obstructive Lung Diseases; Otitis Media; Participant; Patients; Pharmacologic Substance; Phase; Phase III Clinical Trials; Population; Primary Ciliary Dyskinesias; Protocols documentation; Publishing; Randomized, Controlled Trials; Rare Diseases; Recurrence; Research; Research Personnel; Respiratory System; Respiratory Tract Infections; Risk Factors; Sample Size; Science; Sinusitis; Societies; Spirometry; Supervision; Symptoms; System; Testing; Therapeutic; United States National Institutes of Health; Upper Respiratory Infections; Validity and Reliability; clinical care; clinical trial readiness; cohort; electronic patient reported outcomes; epithelial Na+ channel; idiopathic pulmonary fibrosis; inhibitor; instrument; interest; life history; mHealth; member; novel; patient variability; phase I trial; phase III trial; primary endpoint; pulmonary function; rare genetic disorder; respiratory health; secondary endpoint; treatment response; trial planning

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.

项目摘要 在此提案中，我们将建立优化的可行性，可靠性，分析影响和条件 在计划中的3阶段临床试验中使用的移动健康呼吸端点测量质量 原发性睫状运动障碍（PCD）的患者。结果将适用于日益增长的临床 计划在PCD和其他慢性肺部疾病和临床护理环境中进行的试验。 PCD是罕见的 遗传疾病受损伤的粘膜贡清除导致呼吸道慢性细菌感染 区域导致渐进式气道损害和复发性呼吸道加重（RTES）。 联盟大流行已经加速了临床试验设计的范式转变，该试验将试验带到了 患者”通过远程端点确定。作为罕见疾病人群的成员，PCD患者经常 远离研究中心的生活，增加了临床试验参与的障碍。远程端点监视 可以改善获得罕见病群的临床试验的机会。此外，与 可以远程测量哪些端点有可能减少样本量需求的潜力 显示用于测量特发性肺纤维化中的肺功能。 Parion Sciences最近发现了其新型遗传上皮钠的1期试验的希望结果 PCD患者中的通道（ENAC）抑制剂，目前正在计划进行3期随机对照试验。这 拟议的主要和次要终点是一秒钟（FEV1）的强制性到期量 RTES。 Parion有兴趣将这些端点的家庭测量纳入试验。但是，首先， 关于房屋端点测量值的可行性和临床有效性的重要知识差距必须 被解决。 我们向现有的NIH罕见疾病临床研究网络纵向提出了一项辅助研究， 对PCD的儿童和成人队列中RTE的观察性研究。四十名参与者将入学6个 月份。他们将执行家庭肺活量法，并完成一个简单的6项电子患者报告的结果 每周。该研究的目的是评估每周肺活量测定法和RTE的可行性和有效性 检测将这些终点调查到Parion Sciences计划的3阶段临床试验中。这 目的是：1）评估每周进行的家庭肺活量测定法的可行性，可靠性和分析影响 6个月; 2）比较使用使用的两个不同发表的RTE定义的分析影响 每周管理的EPRO 6个月，3）描述肺功能与RTE之间的关联 远程确定。