A new clinical trial evaluating the long-term safety, tolerability, and efficacy of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) triple combination therapy in patients with cystic fibrosis (CF) has just been launched. 

The open-label, phase 3 study aims to recruit 850 patients, aged 12 years and above with the disease who have been treated with the triple combination therapy in one of 2 parent clinical trials.

During this study, participants will receive the combination therapy as oral tablets once a day in the morning for up to 100 weeks. The primary outcome measure will be the safety and tolerability of the treatment as assessed by the number of participants experiencing adverse events and serious adverse events.

Secondary outcome measures will be the absolute change from baseline in percent predicted forced expiratory volume in 1 second and sweat chloride from baseline up to week 96, and the number of pulmonary exacerbations in the same time frame.

The trial has not yet started recruiting participants and the estimated study start date is November 2022. The estimated completion date is October 2025.

Read more about disease-modifying therapies for CF

CF is caused by a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is a channel protein that is normally located on the apical side of epithelial tissue. Its role is to transport chloride and bicarbonate across secretory epithelia.

More than 2000 mutations have been identified in the CFTR gene causing CF. Some of these cause no CFTR protein to be made at all, while others prevent the protein from being transported to the cell membrane, and others yet prevent the protein to open properly and fulfilling its channel function.

VX-121 and tezacaftor are designed to increase the amount of CFTR protein being transported to the cellular membrane. Deutivacaftor is a so-called potentiator that is designed to keep the CFTR protein open for longer to improve the flow of salt and water across the cell membrane.

Reference

A study evaluating the long-term safety and efficacy of VX-121 combination therapy. US National Library of Medicine. Updated July 5, 2022. Accessed July 14, 2022.