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.

Abstract

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.

• Authors: Hector Ortega, Mary Fitzgerald, Kartik Raghupathi, Cindy-Ann Tompkins, Jinshan Shen, Karen Dittrich, Caroline Pattwell, Dave Singh
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 50 Issue 2 Pg. 189-197 (02 2020) ISSN: 1365-2222 [Electronic] England
• PMID: 31659803 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Chemical References

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

Topics

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