Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy: Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial
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, ARC001 Study Group, 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, ARC001 Study Group
Abstract
Background: Peanut 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.
Objective: We performed the first phase 2 multicentered study to assess the safety and efficacy of AR101, a novel oral biologic drug product.
Methods: A 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.
Results: Fifty-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.
Conclusions: In 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.
Keywords: AR101; ARC001; Desensitization; Double-blind placebo-controlled trial; Food allergy; OIT; Oral immunotherapy; Peanut allergy.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed