1st patients dosed in study of inhaled CF treatment ARCT-032
LunairCF trial recruiting patients who don’t use CFTR modulators
Dosing has begun in a Phase 2 clinical study testing ARCT-032, an experimental inhaled treatment Arcturus Therapeutics is developing for cystic fibrosis (CF) patients, including those who don’t benefit from CFTR modulators.
The LunairCF study (NCT06747858) is recruiting adults with a diagnosis of CF who are not eligible for treatment with CFTR modulators or who are not being treated with CFTR modulators because they don’t have access, tolerate, or respond well to them.
The trial, cleared to launch in the U.S. last year, is running at the Cystic Fibrosis Institute of Chicago. Patients who enter LunairCF are assigned to receive either of three dose levels of ARCT-032 every day for four weeks, or about a month. The study has an open-label design, meaning that patients are aware of the treatment they’re receiving.
CF is caused by mutations in the CFTR gene, which has the instructions for producing a protein essential for mucus to be watery in the airways and other organs. If this protein doesn’t work or isn’t produced, thick mucus builds up in the lungs, causing respiratory symptoms.
Cells in the body don’t use a gene’s instructions directly to produce proteins. Instead, they copy the instructions from DNA into a molecule called messenger RNA (mRNA), which carries the instructions to where proteins are produced within cells. ARCT-032 uses fat-coated particles to deliver healthy copies of CFTR mRNA to cells in the lungs, allowing them to produce the protein on their own. Unlike CFTR modulators, this treatment could work for all patients, no matter which mutations they carry.
Addressing ‘significant unmet need’
“ARCT-032 has the potential to address the significant unmet medical need in the CF community for those who do not qualify for or benefit from available treatment options,” Pad Chivukula, PhD, chief scientific officer of Arcturus, said in a company press release.Â
In a Phase 1/1b clinical study (NCT05712538), ARCT-032 was generally safe and well tolerated by healthy adults and patients when inhaled into the lungs via a nebulizer at doses ranging from 3 to 27 mg. Side effects were generally mild, and included elevated temperature with headache, back and muscle pain, and nausea.
Data from four patients who received two doses of ARCT-032 revealed an early trend toward better lung function, with their forced expiratory volume in one second — a measure of how much air can be exhaled in one second — increasing on average by 5.8% after eight days, or five days after the second dose.
The main goal of the LunairCF study is to check how safe ARCT-032 is over 16 weeks (about four months). Other goals include looking at how ARCT-032 moves into, through, and out of the body — its pharmacokinetics — and its effects in respiratory symptoms.
ARCT-032 has been granted rare pediatric disease designation by the U.S. Food and Drug Administration, and orphan drug designation in both the U.S. and the European Union. These designations encourage the development of treatments for rare diseases like CF.
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