Abstract
BackgroundThe Nasal Allergen Challenge (NAC) model allows the study of Allergic Rhinitis (AR) pathophysiology and the proof of concept of novel therapies. The Allergic Rhinitis – Clinical Investigator Collaborative (AR-CIC) aims to optimize the protocol, ensuring reliability and repeatability of symptoms to better evaluate the therapies under investigation.Methods20 AR participants were challenged, with 4-fold increments of their respective allergens every 15 minutes, to determine the qualifying allergen concentration (QAC) at which the Total Nasal Symptom Score (TNSS) of ≥10/12 OR a Peak Nasal Inspiratory Flow (PNIF) reduction of ≥50% from baseline was achieved. At the NAC visit, the QAC was used in a single challenge and TNSS and PNIF were recorded at baseline, 15 minutes, 30 minutes, 1 hour, and hourly up to 12 hours. 10 additional ragweed allergic participants were qualified at TNSS of ≥8/12 AND ≥50% PNIF reduction; the Cumulative Allergen Challenge (CAC) of all incremental doses was used during the NAC visit. 4 non-allergic participants were challenged with the highest allergen concentration.ResultsIn the QAC study, a group qualified by only meeting PNIF criteria achieved lower TNSS than those achieving either TNSS criteria or PNIIF+TNSS (p<0.01). During the NAC visit, participants in both studies reached their peak symptoms at 15minutes followed by a gradual decline, significantly different from non-allergic participants. The “PNIF only” group experienced significantly lower TNSS than the other groups during NAC visit. QAC and CAC participants did not reach the same peak TNSS during NAC that was achieved at screening. QAC participants qualifying based on TNSS or TNSS+PNIF managed to maintain PNIF scores.ConclusionsParticipants experienced reliable symptoms of AR in both studies, using both TNSS and PNIF reduction as part of the qualifying criteria proved better for qualifying participants at screening. Phenotyping based on pattern of symptoms experienced is possible and allows the study of AR pathophysiology and can be applied in evaluation of efficacy of a novel medication. The AR-CIC aims to continue to improve the model and employ it in phase 2 and 3 clinical trials.
Highlights
The Nasal Allergen Challenge (NAC) model allows the study of Allergic Rhinitis (AR) pathophysiology and the proof of concept of novel therapies
The “Total Nasal Symptom Score (TNSS) + Peak Nasal Inspiratory Flow (PNIF)” group achieved similar PNIF falls as the “PNIF only” group and similar TNSS scores to the “TNSS only” group, with no significant difference noted in these comparisons
Clinical responses at NAC during qualifying allergen concentration (QAC) study The mean TNSS and PNIF are plotted for each time point for all 3 groups of participants in the QAC study during the NAC visit (Figure 1A-B)
Summary
The Nasal Allergen Challenge (NAC) model allows the study of Allergic Rhinitis (AR) pathophysiology and the proof of concept of novel therapies. The Allergic Rhinitis – Clinical Investigator Collaborative (AR-CIC) aims to optimize the protocol, ensuring reliability and repeatability of symptoms to better evaluate the therapies under investigation. Allergic rhinitis (AR) is an upper airway inflammatory disease, characterized by symptoms of rhinorrhea, sneezing, and nasal congestion. AR is often considered a benign condition, it greatly impacts the quality of life of affected individuals, with economic costs estimated at $5.3 billion per year in the USA [1,2]. Day-to-day variability in outdoor allergen concentration, effects of weather including temperature and humidity, as well as participant’s lifestyle, can all potentially affect nasal and ocular symptom scores, common outcomes in these studies [5,6]
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