title: Safety of ragweed sublingual allergy immunotherapy tablets in adults with allergic rhinoconjunctivitis.
abstract: A sublingually administered allergy immunotherapy tablet (AIT) is under development to treat ragweed (Ambrosia artemisiifolia)-induced allergic rhinoconjunctivitis (ARC). This study investigates the optimal tolerable dose of once daily ragweed pollen AIT.Subjects 18-50 years old with ragweed-induced ARC were enrolled at two U.S. centers in a double-blind, placebo-controlled,dose-escalation study outside ragweed season. Groups (12 subjects each) were to be randomized 3:1 to 28 days of active treatment (groups assigned in sequence to 3, 6, 12, 24, 50, or 100 units of Ambrosia artemislifolia major allergen 1 [Amb a 1 U],without dose buildup at any level) or matching placebo. Recruitment to 50 Amb a 1-U was discontinued because of adverse events (AEs) after four AIT subjects were enrolled; 100 Amb a 1-U was not initiated. Fifty-three subjects were randomized (AIT,n = 40; placebo, n = 13); four discontinued, all because of AEs (AIT, n = 3; placebo, n = 1). Treatment-related AEs (TRAEs) were more frequent with AIT (73%) than placebo (31%), increasing with dose level. AIT TRAEs were mostly mild (94%) or moderate(5%). No serious TRAEs or anaphylactic shock occurred. The most common TRAEs with AIT were localized pruritus, nasal irritation, and throat irritation. Median onset for common AIT application site reactions was 24 ≤ hours after first treatment (median duration, 15-50 minutes). AIT increased immunoglobulin (Ig) significantly more than placebo (ragweed-specific IgE [6, 12, and 24 Amb a 1-U]; IgG4 [all doses]; p < 0.05). Three subjects in dose groups ≥ 24 Amb a 1-U experienced symptoms suggestive of systemic reaction. Of tested doses, ragweed AIT 24 <Amb a 1-U once-daily was well tolerated in subjects with ragweed-induced ARC. Clinical trial registration URL and registration number: www.clinicaltrials.gov/ct2/show/NCT01134705 [corrected].
authors.affiliation: Sneeze, Wheeze & Itch Associates, LLC, Normal, IL 61761, USA. drnayak@asthma2.com
authors.forename: Anjuli S
authors.initials: AS
authors.lastname: Nayak
authors.forename: George J
authors.initials: GJ
authors.lastname: Atiee
authors.forename: Ea
authors.initials: E
authors.lastname: Dige
authors.forename: Jennifer
authors.initials: J
authors.lastname: Maloney
authors.forename: Hendrik
authors.initials: H
authors.lastname: Nolte
mesh_terms: D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000009:adverse effects*; D031164:Ambrosia / Q000276:immunology*; D003233:Conjunctivitis, Allergic / Q000276:immunology / Q000628:therapy*; D003888:Desensitization, Immunologic / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000485:Allergens