An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment

J Allergy Clin Immunol. 2005 Apr;115(4):791-6. doi: 10.1016/j.jaci.2005.01.040.


Background: R112 inhibits Syk kinase, a transducer of signaling through the Fcepsilon receptor of mast cells, blocking mast cell responses to allergic stimuli.

Objective: Examine the efficacy and safety of intranasal R112 in volunteers with symptomatic seasonal allergic rhinitis compared with a placebo in a park setting.

Methods: In this double-blind, placebo-controlled study of 319 volunteers with seasonal allergic rhinitis, 160 were randomized to intranasal R112 and 159 to a vehicle control during 2 days at 2 separate locations in spring 2004. Subjects were evaluated for symptoms of allergic rhinitis (i.e., sneezes, runny nose/sniffles, itchy nose, stuffy nose) on the basis of a possible maximum score of 32 for the Global Symptom Complex (GSC) scale. The primary outcome evaluated was the difference in the reduction in GSC (area under the curve over a period of 8 hours) from baseline between R112 and vehicle placebo.

Results: At baseline, the combined GSC was approximately 18/32 and equal between treatment groups. After 8 hours (dosing 3 mg/nostril every 4 hours x 2), R112 significantly reduced the GSC compared with placebo (7 vs 5.4 units, respectively; P = .0005). Each individual symptom combined to form the GSC was also significantly improved in the R112 group compared with control ( P < .05). As early as 45 minutes after dosing, R112 showed a significant improvement in symptoms over placebo, and the duration of action exceeded 4 hours. Adverse effects were indistinguishable between the groups and clinically insignificant.

Conclusion: Intranasal R112 was effective in this park study and is a promising new treatment for seasonal allergic rhinitis.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Adolescent
  • Adult
  • Aged
  • Anti-Allergic Agents / administration & dosage*
  • Anti-Allergic Agents / adverse effects*
  • Child
  • Environmental Exposure*
  • Enzyme Inhibitors / administration & dosage
  • Female
  • Humans
  • Male
  • Middle Aged
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Rhinitis, Allergic, Seasonal / drug therapy*
  • ZAP-70 Protein-Tyrosine Kinase


  • Anti-Allergic Agents
  • Enzyme Inhibitors
  • Protein-Tyrosine Kinases
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human