Vertex Pharmaceuticals is set to commence two Phase lll trials of VX-445, tezacaftor and ivacaftor as an investigational triple combination regimen to treat cystic fibrosis (CF) patients.
One of the trials will analyse VX-445 in combination with tezacaftor and ivacaftor, or triple placebo in CF patients aged 12 and older who have one F508del mutation and one minimal function mutation.
The randomised double-blind, placebo-controlled trial seeks to enrol approximately 360 patients.
Its primary endpoint is the mean absolute change in lung function (ppFEV1) from baseline at week four of triple combination treatment compared to triple placebo.
The trial’s key secondary endpoints comprise the number of pulmonary exacerbations, change in body mass index, change in sweat chloride, and change in patient-reported outcomes. These will be measured by the respiratory domain score of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and others.
Furthermore, the trial will investigate VX-445 in combination with tezacaftor and ivacaftor for a total of 24 weeks of treatment to generate additional safety data and data.
During the trial, a fixed-dose combination of 200mg of VX-445, 100mg of tezacaftor and 150mg of ivacaftor in the morning will be given to the patients, followed by 150mg ivacaftor in the evening.
The trial also includes an open-label extension study where all eligible patients, including those who received triple placebo, will be provided with VX-445 triple combination regimen for up to an additional 96 weeks.
The other Phase lll trial is designed to evaluate four weeks of treatment with VX-445 or placebo in combination with tezacaftor and ivacaftor in around 100 patients aged 12 years or older who have two F508del mutations.
As part of the randomised, double-blind, controlled trial, all patients will receive tezacaftor in combination with ivacaftor during a four-week run-in before the starting of the triple combination treatment period.
The trial’s primary endpoint includes the mean absolute change in lung function (ppFEV1) from baseline at week four of treatment with VX-445 in combination with tezacaftor and ivacaftor compared to those who received placebo, tezacaftor and ivacaftor.
Its major secondary endpoints will be measured at week four and feature change in sweat chloride and change in patient-reported outcomes as measured by the CFQ-R respiratory domain score.
The trial will evaluate the same dosing regimen being evaluated in the other Phase lll study of patients with one F508del mutation and one minimal function mutation.