The Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC): verification of nasal allergen challenge procedures in a study utilizing an investigational immunotherapy for cat allergy

Abstract

Background: The Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC) is a network of experienced Allergic Rhinitis (AR) researchers developing better research tools based on the nasal allergen challenge (NAC). A key objective of such is the ability to detect efficacy in a small population. AR-CIC sought to test its NAC protocol as a secondary objective in two small mechanistic research trials of a novel form of immunotherapy [Cat Peptide Antigen Desensitisation (Cat-PAD)] for which efficacy had previously been demonstrated. The primary objective (not presented here) was to identify potential biomarkers of efficacy for peptide immunotherapy, and this provided an ideal opportunity to corroborate the NAC protocol. We aim to clinically validate the AR-CIC NAC methodology in a pooled analysis of secondary endpoints measured in two open label mechanistic studies of cat allergic participants treated with Cat-PAD.

Methods: Cat allergic AR sufferers with ongoing cat exposure were included. Participants had to demonstrate a total nasal symptom score (TNSS) of at least 8 (max 12) and/or achieve a reduction in peak nasal inspiratory flow (PNIF) of ≥ 50% during a screening titrated NAC. Eligible participants then underwent a baseline NAC visit with the allergen dose that produced a positive challenge at screening, followed by four monthly injections of 6 nmol Cat-PAD. A follow up NAC visit documented changes in nasal response 1 month following the completion of treatment.

Results: Nineteen subjects completed the study protocol in the two studies combined. Four injections of Cat-PAD resulted in a significant reduction in TNSS responses generated via NAC following allergen challenge (15 min p < 0.05, 30 min p < 0.05, 1 h p < 0.01, 2 h p < 0.05). There was modest correlation between symptom scores and PNIF measurements.

Conclusions: This study supports the validity of the AR-CIC's optimised NAC protocol for conducting research of the potential efficacy of novel therapeutics in multi-centre studies.Trial registration Both studies reported herein were registered clinicaltrials.gov (NCT01383590 and NCT01383603).

Keywords: Allergic Rhinitis; Cat allergy; Epitope; Immunotherapy; Nasal allergen challenge; Peptide.

Figures

Fig. 1

Study overview. A total of 19 participants completed the study

Fig. 2

TNSS and PNIF data were obtained at baseline, 15, 30 min, 1 h and then hourly for a minimum of 6 h during each NAC visit. Once baseline measurements were recorded, participants received a saline wash of the nasal cavity and were challenged with the qualifying dose of cat dander extract determined during the screening visit

Fig. 3

Effect of Cat-SPIRE on TNSS and PNIF. Participants (n = 19) experienced an initial peak in TNSS and a peak reduction in PNIF at 15 min following allergen challenge, followed by a gradual return to baseline values. Following treatment, participants experienced a significant reduction in TNSS at 15 min (p < 0.05), 30 min (p < 0.05), 1 h (p < 0.01), and 2 h (p < 0.05). Fall in PNIF in response to allergen challenge was also reduced after treatment though not evident in statistical analysis

Fig. 4

Modest correlation between TNSS and PNIF before and following treatment. Every TNSS/PNIF value recorded by each participant at each time point has been plotted separately. The variability in PNIF between participants has resulted in modest correlation (Pre-treatment: R2 = 0.257, p < 0.0001; post-treatment: R2 = 0.270, p < 0.0001). Significant correlation is observed between mean TNSS and mean PNIF across the time course of NAC for both pre-treatment (R2 = 0.941, p < 0.0001) and post-treatment (R2 = 0.95, p < 0.0001) NAC visits