A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In people with CF, this manifests as dysfunction in multiple organ systems including the lungs, pancreas, liver, intestines, skin and others. While nearly 2000 mutations have been described, the most common disease-causing CFTR mutation is F508del, which is found in \>85% of patients followed in the US CF Patient Registry. Two CFTR corrector drugs plus the potentiator ivacaftor have been developed as a triple combination therapy for CF patients with one or two copies of the F508del mutation. We predict that over 90% of CF patients (initially age 12 y/o and above) will be eligible for highly effective CFTR modulator therapy in the U.S. The PROMISE study is designed to measure the direct and indirect CFTR-dependent anion secretion by collecting and analyzing clinical research outcomes and biomarkers on a large number of patients both before and after they begin treatment with elexacaftor, tezacaftor and ivacaftor triple combination therapy (TCT). This study will investigate the impact of TCT across a wide range of CF disease manifestations and organ systems. While specific biomarkers of special interest have been selected for detailed analysis in this study, an additional important goal is to collect blood, urine, stool, and airway epithelial cell specimens for long-term storage in a biorepository to enable future research. These samples can be made available for research beyond the current scope of work. The PROMISE study will provide a coordinated collection of clinical research outcomes data that can be linked with these specimens.