APPLICATION OF ORAL IMMUNOTHERAPY (OIT) CLINICAL TRIAL ENDPOINTS TO A REAL-WORLD SETTING

Abstract

Introduction Double-blind, placebo-controlled food challenges (DBPCFCs) are the gold standard for the diagnosis of food allergy and are being used as clinical trial endpoints for new food allergy therapies. We sought to determine how these endpoints translate into meaningful data that the practicing allergist can use. Methods In the phase 3 study of AR101 for treatment of peanut allergy, DBPCFCs (based on PRACTALL) of 3, 10, 30, 100, 300, 600, and 1000mg of peanut protein at 20-30 minute intervals were used to determine the single-highest dose that a patient could tolerate. Cumulative doses over the entire challenge period were also recorded. Exposure levels to peanut protein were compared to real-world accidental exposure levels and times. Results Of the AR101 patients who completed the study, 85.3% tolerated 600mg as the single-highest tolerated dose and 63% tolerated 1000mg. Using cumulative exposure levels, the mean (sd) time to reach this 1043mg-dose was 122.4 (25.3) mins vs 153.1 (35.1) for the 2043mg group. In comparison, the median dose of peanut consumed upon accidental exposure in a real-world setting was 125mg (IQR 34-177) with symptoms presenting 5-30 minutes post ingestion, suggesting that ability to tolerate at least 600mg of peanut protein in a single exposure is more clinically relevant than the ability to tolerate 1043mg cumulatively over 122.4 mins. Conclusions Symptomatic accidental exposures to peanut often occur at levels greater than 100mg suggesting that the ability to tolerate a single dose of at least 600mg (∼2 peanuts) in a clinical trial may offer clinically relevant protection.