The study (NCT04279769), currently enrolling eligible adults at its two U.S. sites, will test four escalating doses of CB-280 — 50 mg, 100 mg, 200 mg, and 400 mg — against a matching placebo in up to 32 adults with CF and chronic lung infections caused by Pseudomonas aeruginosa. CB-280 and placebo capsules will be taken twice daily for 14 days.
The trial’s primary goal is to determine a safe dose range for CB-280. Additional, or secondary, goals include an assessment of the therapy’s movement into, through, and out of the body. This is known as a treatment’s pharmacokinetic profile.
A previous Phase 1 study in healthy volunteers evaluated the safety, tolerability, and pharmacological profile of this potential small molecule treatment for airway disease in CF.
CB-280 works by inhibiting the enzyme arginase, which is responsible for converting the amino acid arginine into urea and ornithine. Previous research showed that arginase is abnormally active in CF, leading to a shortage of arginine in the lungs. In turn, this shortage reduces anti-microbial airway resistance and lung function.
Higher levels of arginase activity are linked with poorer lung function.
By blocking arginase and raising levels of arginine in the lungs, CB-280 may improve the lungs’ ability to work and to resist to infections, including those due to the bacteria P. aeruginosa.
In CF mouse models of infection, inhibiting arginase and increasing arginine levels bodywide lowered the bacterial burden in mice airways and improved lung health, Calithera reported in a press release.
“Based on preclinical data and the unique pathology of this disease, we believe that CB-280’s mechanism of action represents an opportunity to further improve upon the current standard-of-care for CF patients, for whom there remains great unmet need despite recent therapeutic advancements,” said Susan Molineaux, PhD, president and CEO of Calithera.
“We remain committed to advancing our arginase inhibitor clinical development program to fully explore the potential of this new class of therapeutics in a variety of conditions,” Molineaux added.
The two U.S. sites enrolling patients for Phase 1b trial are the Cystic Fibrosis Institute in Glenview, Illinois, and at the University of Kansas Medical Center in Kansas City. For more information, visit this link.
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