Randomized phase 1 study of the phosphatidylinositol 3-kinase δ inhibitor idelalisib in patients with allergic rhinitis

Background Phosphatidylinositol 3-kinase p110δ isoform (PI3K p110δ) activity is essential for mast cell activation, suggesting that inhibition of PI3K p110δ might be useful in treating allergic diseases. Objective We sought to determine the effect of the PI3K p110δ–selective inhibitor idelalisib on allergic responses. Methods This phase 1 randomized, double-blind, placebo-controlled, 2-period crossover study was conducted with the Vienna Challenge Chamber. Grass pollen–induced allergic symptoms were documented during screening. Eligible subjects received idelalisib (100 mg twice daily) or placebo for 7 days, with allergen challenge on day 7. After a 2-week washout period, subjects received the alternate treatment and repeated allergen challenge. Study measures included safety, nasal and nonnasal symptoms, nasal airflow, nasal secretions, basophil activation, and plasma cytokine levels. Results Forty-one patients with allergic rhinitis received idelalisib/placebo (n = 21) or placebo/idelalisib (n = 20). Idelalisib treatment was well tolerated. Mean total nasal symptom scores were lower during the combined idelalisib treatment periods compared with placebo (treatment difference [idelalisib − placebo], −1.78; 95% CI, −2.53 to −1.03; P ex vivo –activated basophils (CD63 + /CCR3 + cells; after stimulation with grass pollen) was substantially lower for idelalisib-treated compared with placebo-treated subjects. Plasma CCL17 and CCL22 levels were reduced after idelalisib treatment. Conclusion Idelalisib treatment was well tolerated in patients with allergic rhinitis and appears to reduce allergic responses clinically and immunologically after an environmental allergen challenge.