Vertex Pharmaceuticals is set to initiate a Phase III trial of VX-659, tezacaftor, and ivacaftor as a triple combination regimen to treat people with cystic fibrosis (CF) who have one F508del mutation and one minimal function mutation.
The randomised, double-blind, placebo-controlled trial will enrol around 360 patients.
It will examine VX-659 in combination with tezacaftor and ivacaftor, or triple placebo in the enrolled patients who will be aged 12 years and older.
Vertex Pharmaceuticals triple combination steering committee co-chair Steven Rowe said: “There is a significant unmet medical need to treat the underlying cause of CF for those with one F508del mutation and a minimal function mutation, and these patients are eagerly awaiting new treatment options.
“The Phase II data for the triple combination of VX-659, tezacaftor, and ivacaftor showed impressive improvements in multiple measures of CF for patients with minimal function mutations, and I am pleased that this Phase III study is designed to enable rapid advancement of the VX-659 regimen toward patients.”
Primary objective of the new trial is the mean absolute change in lung function (ppFEV1) from baseline at week four of triple combination treatment compared to placebo.
The trial expects to support the submission of a new drug application (NDA) to the US Food and Drug Administration (FDA) based on data received from the four-week primary efficacy analysis and on safety data through 12 weeks of treatment.
During the trial, VX-659 will be studied in combination with tezacaftor and ivacaftor for a total of 24 weeks to generate additional safety data and data for key secondary endpoints such as the number of pulmonary exacerbations, change in body mass index, and change in sweat chloride.
Findings from the trial will also be used to support Vertex’s planned regulatory submissions in Europe and other regions.
In addition, the company is planning to carry out an open-label extension study where all eligible patients, including those who received placebo, will receive the triple combination regimen for up to an additional 96 weeks.