Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy: Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial
Year: 2017
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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.
Institutions: The University of Texas Southwestern Medical Center, Children's Hospital of Philadelphia, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Boston Children's Hospital, Harvard University, Cincinnati Children's Hospital Medical Center, Icahn School of Medicine at Mount Sinai, University of California San Diego, Rady Children's Hospital-San Diego, Allergy and Asthma Medical Group and Research Center, University of North Carolina at Chapel Hill, University of Iowa Hospitals and Clinics
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
Funders: Food Allergy Research and Education, Children's Hospital of Philadelphia, Cincinnati Children's Hospital Medical Center, Harvard Catalyst, Regeneron Pharmaceuticals, Aimmune Therapeutics, Astellas Pharma, National Institutes of Health, Genentech, Astellas Pharma Global Development, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G2661966628, G3615943839, North Carolina Translational & Clinical Sciences Institute (NC TraCS), G626896301, G7060033699, Institutional Clinical and Translational Science Award, Harvard Clinical and Translational Science Center, Mount Sinai Institutes for Clinical and Translational Sciences, G9000307188
OpenAlex ID: W2766193871