Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy

Abstract

Abstract Background The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A ( POLLINEX ® Quattro Plus 1.0 ml Birch 100%) is an effective, well‐tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose. Methods The studies were conducted in Germany, Austria and Poland (Eudra CT numbers: 2012‐004336‐28 PQB irch203 and 2015‐000984‐15 PQB irch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3‐4 weeks after completing treatment, to quantify the reduction in Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modeling analysis was used to test for the dose response, shape of the curve and estimation of the median effective dose ( ED 50 ), a measure of potency. Results Statistically significant dose responses ( P < .01 & .001) were seen, respectively. The highest cumulative dose in PQB irch204 (27 300 standardized units [ SU ]) approached a plateau. Potency of the PQ Birch was demonstrated by an ED 50 2723 SU , just over half the current dose. Prevalence of treatment‐emergent adverse events was similar for active doses, most being short‐lived and mild. Compliance was over 85% in all groups. Conclusion Increasing the cumulative dose of PQ Birch 5.5‐fold from 5100 to 27 300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase in efficacy of 50%, without compromising safety. The cumulative dose response was confirmed to be curvilinear in shape.