• PALISADE Group of Clinical Investigators, Brian P Vickery, Andrea Vereda, Thomas B Casale, Kirsten Beyer, George du Toit, Jonathan O Hourihane, Stacie M Jones, Wayne G Shreffler, Annette Marcantonio, Rezi Zawadzki, Lawrence Sher, Warner W Carr, Stanley Fineman, Leon Greos, Rima Rachid, M Dolores Ibáñez, Stephen Tilles, Amal H Assa’ad, Caroline Nilsson, Ned Rupp, Michael J Welch, Gordon Sussman, Sharon Chinthrajah, Katharina Blumchen, Ellen Sher, Jonathan M Spergel, Frederick E Leickly, Stefan Zielen, Julie Wang, Georgiana M Sanders, Robert A Wood, Amarjit Cheema, Carsten Bindslev-Jensen, Stephanie Leonard, Rita Kachru, Douglas T Johnston, Frank C Hampel, Edwin H Kim, Aikaterini Anagnostou, Jacqueline A Pongracic, Moshe Ben-Shoshan, Hemant P Sharma, Allan Stillerman, Hugh H Windom, William H Yang, Antonella Muraro, José M Zubeldia, Vibha Sharma, Morna J Dorsey, Hey J Chong, Jason Ohayon, J Andrew Bird, Tara F Carr, Dareen Siri, Montserrat Fernández-Rivas, David K Jeong, David M Fleischer, Jay A Lieberman, Dubois Anthony E J AEJ, Marina Tsoumani, Christina E Ciaccio, Jay M Portnoy, Lyndon E Mansfield, Stephen B Fritz, Bruce J Lanser, Jonathan Matz, Hanneke N G Oude Elberink, Pooja Varshney, Stephen G Dilly, Daniel C Adelman, and A Wesley Burks.
• N. Engl. J. Med. 2018 Nov 22; 379 (21): 1991-2001.

BackgroundPeanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.MethodsIn a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.ResultsOf the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older.ConclusionsIn this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

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