The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Abstract

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients.

Priorities and barriers for research related to primary ciliary dyskinesia

“…Top-ranked priorities were related to further improving diagnosis; treating PCD and managing upper and lower airway problems; and studying clinical variability and disease prognosis—all questions considered unlinked to specific disciplines. Our findings become more meaningful in the light of ongoing efforts to develop joint updated diagnostic guidelines for PCD; new potential molecular treatments in the pipeline; and the development of the PCD-specific clinical trials network [41, 42]. Notably, other topics strongly impacting the lives of people with PCD and their families, such as fertility or mental health, ranked lower by experts, although they appeared in the priority list.…”

High diagnostic rate of whole genome sequencing in primary ciliary dyskinesia

“…PCD needs to enter the precision medicine era. A genetic diagnosis is key to improved patient prognosis as we better understand genotype-phenotype relations (69) and critically to being trial-ready as much-needed genetic therapies come online (70,71). Increased genetic testing is also being combined with a curated worldwide database, similar to that of CFTR2 for Cystic Fibrosis (72), to enable a better understanding of these genotype-phenotype relations in PCD called CiliaVar (73).…”

A BEAT-PCD consensus statement: a core outcome set for pulmonary disease interventions in primary ciliary dyskinesia

“…In this study, a large group of stakeholders from different continents has been involved, including Europe, North America, South America and Australia. In addition, some of the co-authors are part of PCD clinical trials network, linking these results to companies and organisations involved in PCD trials [ 12 ].…”

“…Additional clinical trials are needed to assess efficacy of current treatments and explore future treatment opportunities [ 9 ]. Therefore, a disease-specific Clinical Trial Network for Primary Ciliary Dyskinesia has been established [ 12 ].…”

“…[9] Therefore, a disease-specific Clinical Trial Network for Primary Ciliary Dyskinesia (PCD-CTN) has been established. [12] Selection of clinically appropriate and responsive endpoints is of great importance for any clinical trial, but especially in rare diseases, where comparison and meta-analysis of trials are needed. [13,14] Outcomes should be clearly defined as clear definitions are needed to replicate and compare trials.…”