UK Trial to Investigate Safety of Lowering CF Treatment Burden via Kaftrio

The National Institute for Health Research (NIHR) awarded a grant worth more than £1.5 million (about $2.1 million) to support a U.K. clinical trial investigating ways of safely lowering the treatment burden of cystic fibrosis (CF), a top priority for patients and their healthcare teams.

The randomized and open-label trial, called CF STORM, will enroll 764 CF patients across the U.K. on a stable treatment regimen with Kaftrio (by Vertex; sold as Trikafta in the U.S.), a next-generation triple combination therapy, plus a daily nebulized muco-active medication (therapies that help to break down and expel airway mucus).

Enrolled patients will be randomly assigned to either continue their routine care with these two medications, or reduce the burden by stopping treatment with their nebulized muco-active agent (e.g., dornase alfa or hypertonic saline, or both).

Its main goal will be to determine the effects of this change on lung health over the course of one year. Additional goals will look at differences in the frequency of lung infections, patients’ quality of life, and the need for additional treatments, like antibiotics.

According to trial investigators, CF STORM will be pivotal in determining “whether stopping nebulised muco-active treatments for [CF patients] on triple therapy can be confidently recommended with the knowledge that it will not result in a significant reduction in respiratory function.”

Information on study outcomes will be collected during routine medical appointments, and additional hospital visits are not required. If face-to-face appointments are not possible due to the COVID-19 pandemic, remote and home-based consultations will be used.

“People with CF spend many hours every day on multiple treatments, including aerosolised therapies delivered by nebulisers to keep their lungs stable and prevent chest infections,” the NIHR states on its webpage notice. “The recent UK introduction of the highly effective triple therapy drug Kaftrio, which is suitable for many people with CF, provides an ideal opportunity to robustly explore reduction in treatment burden in a clinical trial.”

CF STORM will be carried out at the Liverpool Clinical Trials Centre under the supervision of Kevin Southern, PhD, a professor at the department of Women’s and Children’s Health at the University of Liverpool, and Gwyneth Davies, PhD, NIHR clinical trials fellow at University College London.

“As transformative therapies emerge for CF and other conditions it is important that we evaluate rigorously the impact on the patient journey,” Southern said.

Trial investigators have been working closely with U.K. patient organizations, including the Cystic Fibrosis Trust, to engage patients and their family members with this study’s design and protocol.

A shorter but similar open-label trial, called SIMPLIFY (NCT04378153), is underway in the U.S. SIMPLIFY is evaluating the health of CF patients, ages 12 and older, on a stable Trikafta regimen who stop a nebulized treatment (inhaled hypertonic saline or dornase alfa) compared with those who continue both CF treatments. This trial, in up to 800 patients, runs for six weeks.

SIMPLIFY may still be enrolling patients at sites across the U.S.; information is available here.