2-part trial testing therapy as add-on to Trikafta now fully underway
Enrollment completed for small proof-of-concept study of SION-719
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A small clinical trial testing Sionna Therapeutics‘ SION-719 as an add-on treatment for cystic fibrosis (CF) — to be used alongside the approved CF therapy Trikafta (elexacaftor/tezacaftor/ivacaftor) — has finished enrollment.
The developer announced the milestone in a company press release, noting that top-line data from the proof-of-concept trial are expected this summer.
The Phase 2a PreciSION CF trial (NCT07108153) enrolled an estimated 16 adults with CF in the U.S. and Australia. All were already taking Trikafta.
The study consists of two treatment periods: In the first, some patients will receive add-on treatment with SION-719, while others will be given a placebo. Then, in the trial’s next part, those originally given the placebo will instead get SION-719, and vice versa.
The main goal of this early clinical trial is to evaluate the safety profile of SION-719 when given in combination with Trikafta, which, according to Sionna, is currently the standard-of-care treatment for most people with CF. In a previous trial involving healthy people, SION-719 was overall tolerated well when given on its own.
“Completion of enrollment in our PreciSION CF proof-of-concept trial represents a significant milestone for both Sionna and the cystic fibrosis community,” said Charlotte McKee, MD, Sionna’s chief medical officer.
CF is caused by mutations in the gene that encodes CFTR, a protein that’s vital for regulating mucus production. Lack of functional CFTR leads the body to make unusually thick and sticky mucus, which builds up in the lungs and other organs.
First data on safety of add-on therapy expected this summer
CFTR modulators are a novel class of CF treatments that can boost the activity of the defective protein in people carrying certain mutations. Trikafta, which contains a combination of three such modulators, is widely approved to treat people with CF who have eligible mutations, including the most common CF-causing mutation called F508del.
The researchers noted that all participants in the PreciSION trial are homozygous for F508del, meaning they carry two copies of this specific mutation.
The F508del mutation causes a specific region of the CFTR protein, known as the nucleotide-binding domain 1 or NBD1, to become unstable. As a consequence, the mutated protein is unstable and unable to perform its functions.
Although Trikafta and other currently available modulators can help stabilize the mutated protein, no available therapy specifically targets the NBD1 region. SION-719 is designed to do just that, with the aim of increasing protein activity beyond what’s possible with current therapies.
“This is the first clinical trial evaluating an NBD1 stabilizer in people with CF, marking an important step toward directly addressing the underlying defect of the most common CF-causing mutation,” McKee said.
In addition to evaluating SION-719’s safety, the PreciSION CF study is evaluating how the therapy affects levels of chloride, a type of salt molecule, in sweat. The CFTR protein normally helps control how much chloride is in sweat, and when the protein isn’t working correctly, sweat chloride levels become abnormally high. As such, looking at levels of sweat chloride is a useful proxy for evaluating the effect of treatment on CFTR protein activity.
“We are thankful to the patients, investigators, and the broader CF community for their strong engagement as we advance this trial. We remain focused on executing and look forward to our first data readout in CF patients this summer,” McKee said.
