Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity: A randomized clinical trial

Sampson, Hugh A.; Shreffler, Wayne G.; Yang, William H.; Sussman, Gordon L.; Brown-Whitehorn, Terri F.; Nadeau, Kari C.; Cheema, Amarjit S.; Leonard, Stephanie A.; Pongracic, Jacqueline A.; Sauvage-Delebarre, Christine; Assa’ad, Amal H.; De Blay, Frederic; Bird, J. Andrew; Tilles, Stephen A.; Boralevi, Franck; Bourrier, Thierry; Hébert, Jacques; Green, Todd D.; Gerth Van Wijk, Roy; Knulst, André C.; Kanny, Gisèle; Schneider, Lynda C.; Kowalski, Marek L.; Dupont, Christophe

doi:https://doi.org/10.1001/jama.2017.16591

Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity: A randomized clinical trial

DSpace/Manakin Repository

Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity: A randomized clinical trial

Sampson, Hugh A.; Shreffler, Wayne G.; Yang, William H.; Sussman, Gordon L.; Brown-Whitehorn, Terri F.; Nadeau, Kari C.; Cheema, Amarjit S.; Leonard, Stephanie A.; Pongracic, Jacqueline A.; Sauvage-Delebarre, Christine; Assa’ad, Amal H.; De Blay, Frederic; Bird, J. Andrew; Tilles, Stephen A.; Boralevi, Franck; Bourrier, Thierry; Hébert, Jacques; Green, Todd D.; Gerth Van Wijk, Roy; Knulst, André C.; Kanny, Gisèle; Schneider, Lynda C.; Kowalski, Marek L.; Dupont, Christophe

(2017) JAMA - Journal of the American Medical Association, volume 318, issue 18, pp. 1798 - 1809

(Article)

Abstract

IMPORTANCE: Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. OBJECTIVE: To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. DESIGN, SETTING, AND PARTICIPANTS: Phase 2b double-blind, placebo-controlled, dose-ranging trial ... read more of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016). Patients (n = 221) had peanut sensitivity and positive double-blind, placebo-controlled food challenges to an eliciting dose of 300 mg or less of peanut protein. INTERVENTIONS: Randomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 μg (n = 53), 100 μg (n = 56), or 250 μg (n = 56) of peanut protein or a placebo patch (n = 56). Following daily patch application for 12 months, patients underwent a double-blind, placebo-controlled food challenge to establish changes in eliciting dose. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was percentage of treatment responders (eliciting dose: 10-times increase and/or reaching 1000 mg of peanut protein) in each group vs placebo patch after 12 months. Secondary end points included percentage of responders by age strata and treatment-emergent adverse events (TEAEs). RESULTS: Of 221 patients randomized (median age, 11 years [quartile 1, quartile 3: 8, 16]; 37.6% female), 93.7% completed the trial. A significant absolute difference in response rates was observed at month 12 between the 250-μg (n = 28; 50.0%) and placebo (n = 14; 25.0%) patches (difference, 25.0%; 95% CI, 7.7%-42.3%; P = .01). No significant difference was seen between the placebo patch vs the 100-μg patch. Because of statistical testing hierarchical rules, the 50-μg patch was not compared with placebo. Interaction by age group was only significant for the 250-μg patch (P = .04). In the 6- to 11-year stratum, the response rate difference between the 250-μg (n = 15; 53.6%) and placebo (n = 6; 19.4%) patches was 34.2% (95% CI, 11.1%-57.3%; P = .008); adolescents/adults showed no difference between the 250-μg (n = 13; 46.4%) and placebo (n = 8; 32.0%) patches: 14.4% (95% CI, −11.6% to 40.4%; P = .40). No dose-related serious AEs were observed. The percentage of patients with 1 or more TEAEs (largely local skin reactions) was similar across all groups in year 1: 50-μg patch = 100%, 100-μg patch = 98.2%, 250-μg patch = 100%, and placebo patch = 92.9%. The overall median adherence was 97.6% after 1 year; the dropout rate for treatment-related AEs was 0.9%. CONCLUSIONS AND RELEVANCE: In this dose-ranging trial of peanut-allergic patients, the 250-μg peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01675882.

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Keywords: General Medicine

DOI: https://doi.org/10.1001/jama.2017.16591

ISSN: 0098-7484

Publisher: American Medical Association

Note: Funding Information: contributions were made by Wenceslas Agbotounou, PhD, MBA, Pierre-Henri Benhamou, MD, and Laurent Martin, PharmD, MBA, who are compensated employees of DBV Technologies and were involved in the concept and design of the study. Aurėlie Peillon, MSc, and Robin Mukherjee, PhD, are compensated employees of DBV Technologies who were responsible for acquisition, statistical analyses, and interpretation of data; further statistical support was provided by Soutrik Banerjee, MD, PhD, from Altizem, Boulogne, France, a paid vendor. Jean-Michel Germain, PhD, and Serena Germano, PhD, are compensated employees of DBV Technologies and provided administrative, technical, or material support. Editorial support was provided by Imprint Science, New York, New York, and was funded by DBV Technologies. PRA Health Sciences was the contract research organization for the trial and was also responsible for monitoring all investigational sites, which included ensuring completeness and accuracy of data entries in the case report forms compared with patients’ source documents and adherence to good clinical practices and applicable regulatory requirements. PRA International was responsible for data management and statistical analyses, which included standard edit checks for data accuracy and consistency, as well as production of statistical outputs. In addition, checks of data integrity were performed by DBV Technologies, which included site visits and site audits, as well as contract research organization oversight. Funding Information: Funding/Support: The study was sponsored by DBV Technologies and conducted under an Investigational New Drug application to the US Food and Drug Administration and Clinical Trial Approvals in Canada and European countries. Publisher Copyright: © 2017 American Medical Association. All rights reserved.

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