Validation and Verification of the Allergen Biocube Model with an Intranasal Corticosteroid

Purpose

Controlled clinical models have become an important tool in development and regulatory approval of new therapeutics for allergic rhinitis. For example, Environmental Exposure Units (EEUs) have been used to study presentation of allergic rhinitis and to evaluate therapies in a controlled setting. The ability to elicit allergic rhinitis in a controlled setting provides an opportunity for observation of therapeutic effects in real time as well as a setting in which treatment effects can be precisely monitored. To date, EEUs have been used for Phase II and post-marketing drug development studies. Despite this, these current models do not fully capitalize on their potential to quantify the disease process or the degree to which test interventions modify that process.

Most EEUs suffer from a failure to mimic the normal environmental exposure of allergens that occurs in allergic rhinitis. Often, allergen levels are inconsistent or are delivered doses that may not be clinically relevant. This is likely a key factor in the inability of EEUs to generate reproducible results in clinical studies. This problem is so significant that often the same EEU is unable to duplicate results in similar or identical protocols. In addition, because of their large size (typically 50-150 patients/unit), most current EEUs are ill-suited for capturing objective endpoints with clinician involvement and direct patient observation.

In contrast to other EEUs, Ora has refined its controlled clinical model (Allergen BioCube, ABC) toward two specific goals: (1) to effectively, reproducibly elicit allergic rhinitis signs and symptoms in a well-defined patient population, and (2) to capture clinical effects of test therapies in a controlled manner using both objective and subjective measures in smaller patient populations.

Our goal is to achieve consistent and reproducible results through the use of precision control of our allergen concentration and flow through the ABC, make objective measurements with the use of a dedicated clinician, and quantify clinical changes in a consistent and straight forward manner. We believe that exercising greater control and using clinically significant exposure parameters allows us to more reliably and efficiently show therapeutic drug effects with low standard deviations in data and within a smaller patient population. As part of our second goal, we have developed a proprietary objective scale, the Nasal Inflammation Scale (NIS), to ensure accuracy and reproducibility of assessments.

In this study, we established that our strategy to use precision control and quality together with clinician-informed quantitative measurements produce excellent therapeutic intervention results. Using an intranasal corticosteroids with well-defined efficacy, Flonase®, and controlled priming and test exposures to ragweed within the Ora ABC, we were able to show a significant decrease in instantaneous TNSS scores between the treatment and placebo groups.

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