title: Randomized phase 1 study of the phosphatidylinositol 3-kinase δ inhibitor idelalisib in patients with allergic rhinitis.
abstract: 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.
  
  
  
  We sought to determine the effect of the PI3K p110δ-selective inhibitor idelalisib on allergic responses.
  
  
  
  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.
  
  
  
  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 < .001). Statistically significant differences were also observed for the combined treatment periods for total symptom scores, nasal airflow, nasal secretion weight, and nasal congestion scores. The percentage of 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.
  
  
  
  Idelalisib treatment was well tolerated in patients with allergic rhinitis and appears to reduce allergic responses clinically and immunologically after an environmental allergen challenge.
authors.affiliation: Vienna Challenge Chamber, Vienna, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Horak
authors.affiliation: Gilead Sciences, Seattle, Wash. Electronic address: kpuri@Celgene.com.
authors.forename: Kamal D
authors.initials: KD
authors.lastname: Puri
authors.affiliation: Gilead Sciences, Seattle, Wash.
authors.forename: Bart H
authors.initials: BH
authors.lastname: Steiner
authors.affiliation: Gilead Sciences, Seattle, Wash.
authors.forename: Leanne
authors.initials: L
authors.lastname: Holes
authors.affiliation: Gilead Sciences, Seattle, Wash.
authors.forename: Guan
authors.initials: G
authors.lastname: Xing
authors.affiliation: Vienna Challenge Chamber, Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Zieglmayer
authors.affiliation: Vienna Challenge Chamber, Vienna, Austria.
authors.forename: René
authors.initials: R
authors.lastname: Zieglmayer
authors.affiliation: Vienna Challenge Chamber, Vienna, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lemell
authors.affiliation: Gilead Sciences, Seattle, Wash.
authors.forename: Albert
authors.initials: A
authors.lastname: Yu
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011058:Pollen / Q000276:immunology; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use*; D052999:Quinazolinones / Q000494:pharmacology / Q000627:therapeutic use*; D065631:Rhinitis, Allergic / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000485:Allergens; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines; D052999:Quinazolinones; C552946:idelalisib
keywords: CCL17; CCL22; GS-1101; Phosphatidylinositol 3-kinase; Vienna Challenge Chamber; allergen challenge chamber; allergic rhinitis; grass pollen; idelalisib; p110δ