A Phase 1 Study of Heat/Phenol Killed, E. coli-Encapsulated, Recombinant Modified Peanut Proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the Treatment of Peanut Allergy
Year of Publication
Wood, RA; Stablein, D; Henning, AK; Lindblad, R; Sicherer, SH
AAAAI - American Academy of Allergy, Asthma & Immunology
Journal of Allergy and Clinical Immunology Vol. 129, Issue 2, Supplement, Page AB27
RATIONALE: To investigate the safety and immunologic effects of a vaccine containing modified peanut proteins. METHODS: This was a Phase 1, two-center, non-randomized, open label trial of EMP-123, a rectally administered solution of recombinant Ara h 1, Ara h 2 and Ara h 3, modified by amino acid substitutions at major IgE binding epitopes, encapsulated in heat/phenol killed E. coli. EMP123 was administered to 5 healthy adults for 4 weekly escalating doses and then to 10 peanut allergic adults by weekly dose escalation over 10 weeks from 10mcg to 3063mcg, followed by 3 biweekly doses of 3063 mcg. RESULTS: There were no significant adverse effects in the healthy volunteers. Of the 10 peanut allergic subjects [4 with intermittent asthma, median age 24yrs (range, 19-35), peanut-IgE 33.3kUA/L (7.2-120.2), peanut prick skin test wheal 11.3mm (6.5-18)], 4 experienced no adverse reactions, one had mild rectal symptoms, 3 were discontinued per protocol with mild-moderate allergic reactions, and 2 were discontinued with severe allergic reactions at doses of 875mcg and 3063mcg. Median baseline peanut IgE was significantly higher in the 5 reactive subjects (82.4 versus 17.2kUA/L, p50.032), as was baseline anti-Ara h2 IgE (43.3 versus 8.3, p50.036). Peanut skin titration was significantly reduced from baseline (p50.02) but no significant changes were detected for total IgE, peanut IgE, peanut IgG4, or basophil activation (CD63+, CD203+). CONCLUSIONS: Rectal administration of EMP123 resulted in frequent adverse reactions, including severe allergic reactions in 20% with peanut allergy. Further modifications to the product and/or dosing scheme will be necessary to decrease adverse reactions.