A randomized controlled phase II clinical trial comparing ONO‐4053, a novel DP1 antagonist, with a leukotriene receptor antagonist pranlukast in patients with seasonal allergic rhinitis

Abstract

BackgroundProstaglandin D2 (PGD 2) is primarily produced by mast cells and is contributing to the nasal symptoms including nasal obstruction and rhinorrhea.ObjectiveThis study aimed to evaluate the efficacy and safety of a novel PGD 2 receptor 1 (DP1) antagonist, ONO‐4053, in patients with seasonal allergic rhinitis (SAR).MethodsThis study was a multicenter, randomized, double‐blind, parallel‐group study of patients with SAR. Following a one‐week period of placebo run‐in, patients who met the study criteria were randomized to either the ONO‐4053, leukotriene receptor antagonist pranlukast, or placebo group for a two‐week treatment period. A total of 200 patients were planned to be randomly assigned to receive ONO‐4053, pranlukast, or placebo in a 2:2:1 ratio. Nasal and eye symptoms were evaluated.ResultsBoth ONO‐4053 and pranlukast had higher efficacy than placebo on all nasal and eye symptoms. ONO‐4053 outperformed pranlukast in a total of three nasal symptom scores (T3NSS) as well as in individual scores for sneezing, rhinorrhea, and nasal itching. For T3NSS, the Bayesian posterior probabilities that pranlukast was better than placebo and ONO‐4053 was better than pranlukast were 70.0% and 81.6%, respectively, suggesting that ONO‐4053 has a higher efficacy compared with pranlukast. There was no safety‐related issue in this study.ConclusionsWe demonstrated that the efficacy of ONO‐4053 was greater than that of pranlukast with a similar safety profile. This study indicates the potential of ONO‐4053 for use as a treatment for SAR (JapicCTI‐142706).

Prostaglandin D2 receptors in human mast cells

“…As shown in Figure 2D, the majority of basophils (mean ± SD-80.93% ±16. 7) expressed DP2 while only a minor population of mast cells from polyps (mean ± SD-8.83% ±7.3) or from nasal turbinates (mean ± SD-6.81% ±8.1) showed weak positive staining for this receptor. Thus, our data would support the hypothesis that the majority of primary human mast cells do not express PGD 2 receptors, cannot be activated by PGD 2 and as a result would not be effectively targeted by selective PGD 2 receptor antagonists.…”

“…4,5 As a number of novel antagonists for PGD 2 receptors have entered clinical trials, information regarding whether human mast cells could be a target for this new class of drugs seems to be of particular interest. 6,7 In order to analyze whether human mast cells may be activated by PGD 2 , we first examined the expression of PGD 2 and cysLTs receptors at the mRNA level in two human mast cell lines, LAD2 and LUVA ( Figure 1A). Interestingly, LUVA cells expressed high levels of PTGDR2 (gene encoding PGD2 receptor type 2, DP2, also known as CRTH2 and CD294) in comparison with much lower levels detected in LAD2 cells.…”

Novel innate and adaptive lymphocytes: The new players in the pathogenesis of inflammatory upper airway diseases

“…The defect of NK cells in CRS was possibly induced by PGD2, which worked through the D prostanoid receptor 1 (DP1) rather than the DP2 (also termed CRTH2) . Therefore, blocking DP1 by ONO‐4053, a novel DP1 antagonist, may also have clinical implication to improve NK cell function and alleviate eosinophilic inflammation in CRS …”

“…19 Therefore, blocking DP1 by ONO-4053, a novel DP1 antagonist, may also have clinical implication to improve NK cell function and alleviate eosinophilic inflammation in CRS. 109…”

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

“…[3][4][5][6][7][8] In addition, a number of promising small molecule drugs and vaccines are in the development pipeline. [9][10][11] This new era is now calling for the development of biomarkers and phenoand endotyping of diseases for customized patient care, which is termed stratified medicine, precision medicine, or personalized medicine. 4 Distinguishing phenotypes of a complex disease covers the observable clinically relevant properties of the disease but does not show a direct relationship to disease etiology and pathophysiology.…”