Phase 1 trial testing CFTR modulator add-on therapy KIT2014
In preclinical studies, treated increased modulator effects by up to 80%
A Phase 1 trial that’s evaluating the safety and tolerability of an inhaled treatment called KIT2014 in healthy volunteers has started in Australia.
KIT2014 is being developed by Kither Biotech as an add-on to existing CTFR modulators, to improve lung function and reduce inflammation in cystic fibrosis (CF) patients.
“The initiation of this Phase 1 study marks a significant step forward for Kither Biotech and the CF community,” Dimitrios Goundis, PhD, the company’s CEO, said in a company press release.
CF is caused by mutations in the gene CTFR that provides instructions for making a protein of the same name. The CTFR protein acts as a gate, controlling the movement of chloride into and out of the cell, which is critical for mucus production.
CTFR mutations lead to abnormally thick and sticky mucus being produced, particularly in the lungs, pancreas, digestive tract, and reproductive system. CF symptoms include shortness of breath, frequent lung infections, and digestive issues.
What is KIT2014?
KIT2014 is a peptide-based therapy that’s inhaled directly into the lungs. According to Kither, it works in several ways. First, the therapy increases levels of cyclic adenosine monophosphate (cAMP), a signaling molecule associated with less inflammation. Increasing cAMP improves both CFTR function as a gate and chloride transport in cells that line the airways. In airway smooth muscle cells, increasing cAMP causes the airways to relax. The therapy also is believed to reduce inflammation driven by neutrophils, a type of immune cell.
CFTR modulators are a class of medications designed to boost the functionality of the CFTR protein. Although these treatments are effective at easing CF symptoms and slowing disease progression, some patients may continue having inflammation and infections, which negatively impacts lung function and overall health.
“KIT2014 addresses mucus obstruction, chronic inflammation, and bronchoconstriction-three critical challenges that affect CF patients even with current CFTR modulators,” Goundis said.
The Phase 1 clinical trial (NCT06659757) plans to enroll 72 healthy adults and will be conducted in two parts. In the first part, it will assess the safety and tolerability of a single ascending dose of the therapy compared with a placebo. Up to six different doses will be tested. In the second part, multiple ascending doses, up to three of them, will be evaluated, also relative to the placebo.
Besides tracking adverse events, the scientists plan to study pharmacokinetics, which is the movement of a therapy into, through, and out of the body.
In preclinical studies using airway cells from CF patients, researchers found that adding KIT2014 increased the effects of CTFR modulators by up to 80%. The therapy also relaxed airways and reduced inflammation in a mouse model of asthma.
“We are excited to begin assessing the potential of KIT2014 to improve treatment outcomes,” Goundis said.
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