SummaryBackgroundCat‐PAD, the first in a new class of synthetic peptide immuno‐regulatory epitopes (SPIREs), was shown to significantly improve rhinoconjunctivitis symptoms in subjects with cat allergy up to 1 year after the start of a short course of treatment.ObjectiveTo evaluate the long‐term effects of Cat‐PAD on rhinoconjunctivitis symptoms following standardized allergen challenge 2 years after treatment.MethodsIn a randomized, double‐blind, placebo‐controlled, parallel group study, subjects were exposed to cat allergen in an environmental exposure chamber (EEC) before and after treatment with two regimens of Cat‐PAD (either eight doses of 3 nmol or four doses of 6 nmol) given intradermally over a 3‐month period. In this follow‐up study, changes from baseline in rhinoconjunctivitis symptoms were reassessed 2 years after the start of treatment.ResultsThe primary endpoint showed a mean reduction in total rhinoconjunctivitis symptom scores of 3.85 units in the 4 × 6 nmol Cat‐PAD group compared to placebo 2 years after the start of treatment (P = 0.13), and this difference was statistically significant in the secondary endpoint at the end of day 4 when the cumulative allergen challenge was greatest (P = 0.02). Consistent reductions in nasal symptoms of between 2 and 3 units were observed for 4 × 6 nmol Cat‐PAD compared to placebo between the 2 and 3 h time points on days 1–4 of EEC challenge at 2 years (P < 0.05). The 8 × 3 nmol dose did not show a meaningful effect in this study.Conclusion and Clinical RelevanceA persistent, clinically meaningful reduction in rhinoconjunctivitis symptoms was observed on EEC challenge 2 years after the start of a short course of treatment with 4 × 6 nmol Cat‐PAD. This study is the first to provide evidence of a long‐term therapeutic effect with this new class of SPIREs.

RationalePreviously, we demonstrated a series of Synthetic Peptide Immuno-Regulatory Epitopes (SPIRE) derived from grass allergens resulted in a statistically significant reduction in rhinoconjunctivitis symptoms in an Environmental Exposure Unit (EEU), following a short course of treatment over 14 weeks and subsequent exposure to the natural grass pollen season. Here we evaluate whether the treatment effect persisted after a second grass pollen season without further dosing.MethodsThis was a double-blind, optional follow-up study to a multi-centre, randomised, double-blind, placebo-controlled, parallel group study. Subjects who had mean baseline TRSS of >8 completing the original study in 2012 were invited to participate. EEU visits were scheduled after a second grass pollen season, approximately 1 year after the original post-treatment EEU challenge. There were no further administrations of Grass-SPIRE.ResultsEight administrations of 6 nmol Grass-SPIRE over a 14 week period showed a mean change in TRSS scores at EEU challenge, after two intervening grass pollen seasons off treatment, of -6.0 versus -3.6 on placebo (p=0.0535). The reduction in mean TRSS for the 6 nmol dose out performed two higher 12 nmol doses.ConclusionsTreatment with Grass-SPIRE over 14 weeks showed a sustained treatment effect in grass allergy symptoms in an EEU model of grass allergy measured after two intervening grass pollen seasons following the cessation of dosing. These results for Grass-SPIRE showing a persistent treatment effect are similar to those obtained with other SPIREs, including cat and house dust mite. RationalePreviously, we demonstrated a series of Synthetic Peptide Immuno-Regulatory Epitopes (SPIRE) derived from grass allergens resulted in a statistically significant reduction in rhinoconjunctivitis symptoms in an Environmental Exposure Unit (EEU), following a short course of treatment over 14 weeks and subsequent exposure to the natural grass pollen season. Here we evaluate whether the treatment effect persisted after a second grass pollen season without further dosing. Previously, we demonstrated a series of Synthetic Peptide Immuno-Regulatory Epitopes (SPIRE) derived from grass allergens resulted in a statistically significant reduction in rhinoconjunctivitis symptoms in an Environmental Exposure Unit (EEU), following a short course of treatment over 14 weeks and subsequent exposure to the natural grass pollen season. Here we evaluate whether the treatment effect persisted after a second grass pollen season without further dosing. MethodsThis was a double-blind, optional follow-up study to a multi-centre, randomised, double-blind, placebo-controlled, parallel group study. Subjects who had mean baseline TRSS of >8 completing the original study in 2012 were invited to participate. EEU visits were scheduled after a second grass pollen season, approximately 1 year after the original post-treatment EEU challenge. There were no further administrations of Grass-SPIRE. This was a double-blind, optional follow-up study to a multi-centre, randomised, double-blind, placebo-controlled, parallel group study. Subjects who had mean baseline TRSS of >8 completing the original study in 2012 were invited to participate. EEU visits were scheduled after a second grass pollen season, approximately 1 year after the original post-treatment EEU challenge. There were no further administrations of Grass-SPIRE. ResultsEight administrations of 6 nmol Grass-SPIRE over a 14 week period showed a mean change in TRSS scores at EEU challenge, after two intervening grass pollen seasons off treatment, of -6.0 versus -3.6 on placebo (p=0.0535). The reduction in mean TRSS for the 6 nmol dose out performed two higher 12 nmol doses. Eight administrations of 6 nmol Grass-SPIRE over a 14 week period showed a mean change in TRSS scores at EEU challenge, after two intervening grass pollen seasons off treatment, of -6.0 versus -3.6 on placebo (p=0.0535). The reduction in mean TRSS for the 6 nmol dose out performed two higher 12 nmol doses. ConclusionsTreatment with Grass-SPIRE over 14 weeks showed a sustained treatment effect in grass allergy symptoms in an EEU model of grass allergy measured after two intervening grass pollen seasons following the cessation of dosing. These results for Grass-SPIRE showing a persistent treatment effect are similar to those obtained with other SPIREs, including cat and house dust mite. Treatment with Grass-SPIRE over 14 weeks showed a sustained treatment effect in grass allergy symptoms in an EEU model of grass allergy measured after two intervening grass pollen seasons following the cessation of dosing. These results for Grass-SPIRE showing a persistent treatment effect are similar to those obtained with other SPIREs, including cat and house dust mite.