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.

项目概要 在本提案中，我们将建立可行性、可靠性、分析影响和优化的条件 移动健康呼吸终点测量的质量，用于计划中的 3 期临床试验 原发性纤毛运动障碍（PCD）患者的研究结果将适用于越来越多的临床。 计划进行的 PCD 试验以及其他慢性肺部疾病和临床护理机构的试验是罕见的。 粘液纤毛清除功能受损导致呼吸道慢性细菌感染的遗传性疾病 导致进行性气道损伤和反复呼吸道恶化（RTE）。 新冠疫情大流行加速了临床试验设计的范式转变，“将试验带到了 PCD 患者通常属于罕见病人群。 居住地远离研究中心，增加了参与临床试验的障碍。 可以改善罕见疾病人群进行临床试验的机会。 哪些端点可以远程测量有可能降低样本量要求，就像 已被证明可用于测量特发性肺纤维化的肺功能。 Parion Sciences 最近发现其新型吸入上皮钠的一期试验有希望的结果 通道（ENaC）抑制剂用于 PCD 患者，目前正在计划进行 3 期随机对照试验。 建议的主要和次要终点是一秒用力呼气量 (FEV1) 和呼气速率 然而，RTE 有兴趣将这些终点的家庭测量纳入试验中。 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 得到解决。 我们提议对现有的 NIH 罕见病临床研究网络纵向进行一项辅助研究， 将招募 40 名患有 PCD 的儿童和成人进行 RTE 观察研究。 他们将进行家庭肺活量测定并完成简单的 6 项电子患者报告结果。 该研究的目的是评估每周家庭肺活量测定和 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。 目标是： 1) 评估每周进行的家庭肺活量测定的可行性、可靠性和分析影响 6 个月；2) 比较使用 RTE 检测到的两种不同已发布定义的分析影响 每周一次 ePRO，持续 6 个月，3) 描述肺功能和 RTE 之间的关联 远程确定。