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

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.