Safety and Tolerability of Escalating Doses of House Dust Mite- Peptide Antigen Desensitization (HDM-PAD)

Abstract

S A T U R D A Y 135 Safety and Tolerability of Escalating Doses of House Dust MitePeptide Antigen Desensitization (HDM-PAD) Mark Larche, Pascal Hickey, Jacques Hebert, MD, Rod Hafner, PhD; Division of Clinical Immunology & Allergy, Department of Medicine, McMaster University, Hamilton, ON, Canada, Adiga Life Sciences, Hamilton, ON, Canada, Centre de Recherche Applique en Allergie de Quebec, Quebec City, QC, Canada, Circassia, Oxford, United Kingdom. RATIONALE: House Dust Mite (HDM) accounts for 20-25% of the allergic rhinoconjunctivitis disease burden worldwide. This study used peptide antigen desensitization (PAD) consisting of T-cell epitopes from major HDM-allergens and evaluated its safety and efficacy. METHODS: T-cell epitopes were identified by algorithm, manufactured, and screened in ex vivo blood samples from HDM-allergic subjects. A second group of HDM-allergic subjects attended Baseline Challenge where Early and Late Phase Skin Responses (EPSR) (LPSR), and Conjunctival Provocation Test (CPT) response were measured. Subjects were randomised to 5 cohorts comprising 8 subjects receiving HDM-PAD (also known as ToleroMune HDM) and 2 subjects receiving placebo. Successive cohorts received 4 administrations 4-weeks apart of 0.03, 0.3, 1.0, 3.0 and 12nmol, respectively. EPSR, LPSR and CPTwere re-measured 18-22 weeks after first administration. RESULTS: HDM-PADwas safe andwell tolerated. Therewere no Serious Adverse Events. The most commonly reported TEAEs were nasopharyngitis, influenza, gastroenteritis and nausea. HDM-PAD did not induce changes in mean FEV1 post-dose. Four HDM-PAD treatment arms resulted in CPT score changes between -16.7% to -41.4% (placebo no change). Median % change in CPT score of -36.7% (p50.0257 vs. placebo) and the largest change in EPSR (median % change -39.19%) and LPSR (median % change -51.19%) was observed after 3nmol HDM-PAD. CONCLUSIONS: HDM-PAD is safe and well tolerated when given as four intradermal injections 4-weeks apart. Reductions in the EPSR, LPSR and CPT indicate that the identified T-cell epitopes have biological activity and merit further evaluation for treatment of HDM allergy.