A phase 2 study to evaluate the safety, efficacy and pharmacokinetics of DP2 antagonist GB001 and to explore biomarkers of airway inflammation in mild-to-moderate asthma

Clin Exp Allergy. 2020 Feb;50(2):189-197. doi: 10.1111/cea.13524. Epub 2019 Nov 26.


Background: GB001 is an oral antagonist of the prostaglandin D2 receptor that may inhibit recruitment and activation of airway eosinophils, reducing airway inflammation.

Objective: To assess GB001 safety, efficacy and pharmacokinetics from a Phase 2 study and explore the association between type 2 biomarkers (fractional exhaled nitric oxide and blood eosinophils) and asthma control markers following GB001 administration.

Methods: A randomized, placebo-controlled, double-blind study evaluating 36 patients with mild-to-moderate atopic asthma. Patients receiving fluticasone propionate ≤500 mcg/day or equivalent were randomized (2:1) to GB001 (30 mg) or placebo once daily for 28 days. Safety, pharmacokinetics, forced expiratory volume in 1 second, asthma control questionnaire and rescue medication use were assessed. Clinical outcomes were analysed post hoc by baseline fractional exhaled nitric oxide (<35 and ≥35 ppb) and blood eosinophil (<250 and ≥250 cells/µL) subgroups.

Results: GB001 was well tolerated and rapidly absorbed with a 14.5-hour terminal half-life. Overall, GB001 demonstrated greater improvement relative to placebo in forced expiratory volume in 1 second at Day 28 (102 mL [95% CI: -110, 314]). Greater effects on forced expiratory volume in 1 second were observed in the high baseline fractional exhaled nitric oxide and blood eosinophil subgroups (207 mL [95% CI: -283, 698];133 mL [95% CI: -422, 687], respectively). These effects were observed as early as Day 2 (229 mL [95% CI: -170, 628]; 163 mL [95% CI: -223, 550] for the high baseline fractional exhaled nitric oxide and blood eosinophil subgroups, respectively) and were sustained through treatment completion.

Conclusion and clinical relevance: GB001 was well tolerated, with the estimated half-life supporting once-daily (QD) dosing. GB001 may have a rapid and sustained effect on lung function, particularly in patients with type 2 phenotype. Further studies are needed to confirm these findings.

Trial registration: ClinicalTrials.gov NCT03683576.

Keywords: CRTH2; DP2 antagonist; atopic asthma; eosinophilic asthma; prostaglandin D2.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Anti-Asthmatic Agents* / administration & dosage
  • Anti-Asthmatic Agents* / adverse effects
  • Anti-Asthmatic Agents* / pharmacokinetics
  • Asthma* / drug therapy
  • Asthma* / immunology
  • Asthma* / pathology
  • Biomarkers
  • Breath Tests
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / immunology
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Receptors, Prostaglandin / immunology


  • Anti-Asthmatic Agents
  • Biomarkers
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostaglandin D2 receptor

Associated data

  • ClinicalTrials.gov/NCT03683576