Novel outcome measures for clinical trials in cystic fibrosis

Harm A.W.M Tiddens,Scott H Donaldson,David A Waltz,Stephanie D Davis,Steven M Rowe,Mark Higgins,Jose G Venegas,Felix Ratjen,Michael Puderbach,Scott D Sagel

doi:10.1002/ppul.23146

Abstract

Cystic fibrosis (CF) is a common inherited condition caused by mutations in the gene encoding the CF transmembrane regulator protein. With increased understanding of the molecular mechanisms underlying CF and the development of new therapies there comes the need to develop new outcome measures to assess the disease, its progression and response to treatment. As there are limitations to the current endpoints accepted for regulatory purposes, a workshop to discuss novel endpoints for clinical trials in CF was held in Anaheim, California in November 2011. The pros and cons of novel outcome measures with potential utility for evaluation of novel treatments in CF were critically evaluated. The highlights of the 2011 workshop and subsequent advances in technologies and techniques that could be used to inform the development of clinical trial endpoints are summarized in this review. Pediatr Pulmonol. © 2014 The Authors. Pediatric Pulmonology published by Wiley Periodicals, Inc.

Highlights

Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein, an ion channel that transports chloride ions across epithelial cell membranes
The aim of this review is to summarize the highlights of this workshop, together with more recent developments of clinical trial endpoints for CF, in order to identify potential alternatives that may be useful in future studies
Evaluation of the ability of chest computed tomography (CT) to identify lung abnormalities not detected by spirometry is an important step in validating its use in the diagnosis and monitoring of CF lung disease.[51,52]

Summary

Introduction

Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein, an ion channel that transports chloride ions across epithelial cell membranes. As life expectancy improves and decline in lung function is reduced, the traditional endpoints for studies in patients with CF, such as spirometry parameters, are becoming less appropriate for assessing drug effects.[4] In addition, newborn screening has been widely adopted and the introduction of disease-modifying therapies aimed at correcting the function of the defective CFTR protein[5] that could be started early in life seems imminent, following the recent approval of the first CFTR potentiator.[6] there is a need for novel endpoints that allow detection of clinical benefits starting in young children and continuing into adulthood, which are acceptable to regulatory authorities. More sensitive outcome measures may assist identification of individuals who could benefit from a novel therapy, reduce the sample size and shorten the duration of intervention studies.[4]

Objectives

Results

Conclusion