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

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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.