Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy: Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial

Publication date: March–April 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice, Volume 6, Issue 2
Author(s): J. Andrew Bird, Jonathan M. Spergel, Stacie M. Jones, Rima Rachid, Amal H. Assa'ad, Julie Wang, Stephanie A. Leonard, Susan S. Laubach, Edwin H. Kim, Brian P. Vickery, Benjamin P. Davis, Jennifer Heimall, Antonella Cianferoni, Andrew J. MacGinnitie, Elena Crestani, A. Wesley Burks
BackgroundPeanut oral immunotherapy, using a variety of approaches, has been previously shown to induce desensitization in peanut-allergic subjects, but no products have been approved for clinical use by regulatory agencies.ObjectiveWe performed the first phase 2 multicentered study to assess the safety and efficacy of AR101, a novel oral biologic drug product.MethodsA randomized, double-blind, placebo-controlled trial was conducted at 8 US centers. Eligible subjects were 4 to 26 years old, sensitized to peanut, and had dose-limiting symptoms to ≤143 mg of peanut protein in a screening double-blind, placebo-controlled food challenge (DBPCFC). Subjects were randomized 1:1 to daily AR101 or placebo and gradually up-dosed from 0.5 to 300 mg/day. The primary endpoint was the proportion of subjects in each arm able to tolerate ≥443 mg (cumulative peanut protein) at exit DBPCFC with no or mild symptoms.ResultsFifty-five subjects (29 AR101, 26 placebo) were enrolled. In the intention-to-treat analysis, 23 of 29 (79%) and 18 of 29 (62%) AR101 subjects tolerated ≥443 mg and 1043 mg at exit DBPCFC, respectively, versus 5 of 26 (19%) and 0 of 26 (0%) placebo subjects (both P < .0001). Compared with placebo, AR101 significantly reduced symptom severity during exit DBPCFCs and modulated peanut-specific cellular and humoral immune responses. Gastrointestinal (GI) symptoms were the most common treatment-related adverse events (AEs) in both groups, with 6 AR101 subjects (21%) withdrawing, 4 of those due primarily to recurrent GI AEs.ConclusionsIn this study, AR101 demonstrated an acceptable safety profile and demonstrated clinical activity as a potential immunomodulatory treatment option in peanut-allergic children over the age of 4, adolescents, and young adults.