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Clinical Trial
. 2025 Mar;80(3):827-842.
doi: 10.1111/all.16420. Epub 2024 Dec 14.

Dupilumab as an Adjunct to Oral Immunotherapy in Pediatric Patients With Peanut Allergy

R Sharon Chinthrajah  1 , Sayantani B Sindher  1 , Kari C Nadeau  2 , Jeffrey G Leflein  3 , Jonathan M Spergel  4 , Daniel H Petroni  5 , Stacie M Jones  6 , Thomas B Casale  7 , Julie Wang  8 , Warner W Carr  9 , Wayne G Shreffler  10 , Robert A Wood  11 , Erik Wambre  12 , Jinzhong Liu  13 , Bolanle Akinlade  13 , Amanda Atanasio  13 , Jamie M Orengo  13 , Jennifer D Hamilton  13 , Mohamed A Kamal  13 , Andrea T Hooper  13 , Kiran Patel  14 , Elizabeth Laws  15 , Leda P Mannent  16 , Daniel C Adelman  17   18 , Anoshie Ratnayake  18 , Allen R Radin  13
Affiliations
Clinical Trial

Dupilumab as an Adjunct to Oral Immunotherapy in Pediatric Patients With Peanut Allergy

R Sharon Chinthrajah et al. Allergy. 2025 Mar.

Abstract

Background: Peanut allergy is a common, life-threatening food allergy in children. We evaluated whether dupilumab, which blocks the activity of interleukin (IL)-4/IL-13, enhances the efficacy of oral immunotherapy (OIT) AR101 in pediatric patients with peanut allergy.

Methods: A Phase II, multicenter, randomized, double-blind study was conducted in the USA (NCT03682770) in pediatric patients (6-≤ 17 years old) with confirmed peanut allergy. Patients were randomized 2:1 to receive dupilumab + OIT or placebo + OIT during a 28-40-week up-dosing period. Patients in the dupilumab + OIT group were re-randomized 1:1 and received dupilumab + OIT or placebo + OIT during 24-week OIT maintenance, undergoing a 2044 mg (cumulative) of peanut protein double-blind, placebo-controlled food challenge (DBPCFC) following up-dosing, maintenance, and at 12-week post-treatment follow-up.

Results: The study enrolled 148 patients, 123 of whom were included in the modified full analysis set, with a mean age of 11.1 years. Dupilumab + OIT treatment (n = 84) led to a 20.2% increase (p < 0.05) in the number of patients who passed a DBPCFC to 2044 mg (cumulative) of peanut protein following the up-dosing period versus placebo (OIT alone, n = 39). Following the OIT maintenance period, continuous dupilumab treatment improved the number of patients who passed a DBPCFC to 2044 mg (cumulative) of peanut protein versus patients continuously on OIT alone (16.6% difference [95% CI -9.7, 42.8], p = 0.2123). Safety was consistent with known dupilumab safety profile.

Conclusions: Dupilumab provided a modest increase efficacy of OIT in children and adolescents with peanut allergy, though it did not provide protection against OIT-related anaphylaxis.

Trial registration: ClinicalTrials.gov identifier: NCT03793608.

Keywords: OIT; children; dupilumab; peanut allergy.

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Conflict of interest statement

R.S.C. has received research grants from Aimmune, Astellas, AstraZeneca, Consortium for Food Allergy Research, DBV Technologies, Food Allergy Research & Education, National Institute of Allergy and Infectious Disease, Novartis, Regeneron, and has been an advisory board member for Alladapt, Allergenis, Intrommune Therapeutics, Genentech, Novartis, Sanofi. S.B.S. reports research grants from Aimmune, the Consortium for Food Allergy Research (CoFAR), FARE, DBV Technologies, the National Institute of Allergy and Infectious Diseases (NIAID), Novartis, Regeneron Pharmaceuticals Inc., and Sanofi, and is an advisory board member for DBV Technologies and a consultant for Genentech. K.C.N. has received research grants from Food Allergy Research & Education, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, holds stock options in ClostraBio, IgGenix, ImmuneID, Seed Health, is involved in directorship for World Allergy Organization Center of Excellence for Stanford, is an advisor for Cour Pharma, receives consultancy fees from Eli Lilly, Excellergy, Phylaxis, Red Tree Ventures, is a co‐founder of Alladapt, Before Brands, ClostraBio, IgGenix, ImmuneID, Latitude, Seed Health, is a National Scientific Committee member for Immune Tolerance Network, National Institutes of Health clinical research centers, has issued patents (US12/686,121 and US12/610,94), and is a licensee (US15/048,609). J.G.L. has no conflicts to disclose. J.M.S. has received research grants from National Institutes of Health, Regeneron/Sanofi, has received consultancy fees from Allakos, Celgene, Regeneron/Sanofi, and has received royalties from UpToDate. D.H.P. has received speakers' bureau fees from AstraZeneca and is a consultant for HollisterStier. S.M.J. has received grants and/or contracts for the conduct of research and clinical trials from Aimmune Therapeutics, ALK‐Abello Inc., Aravax, PTY, Astellas Pharma Inc., DBV Technologies, Genentech, Novartis, Regeneron, and Food Allergy Research and Education (FARE), NIH‐NIAID, Immune Tolerance Network, and she serves on the board of directors for LAmAb Bio Inc. T.B.C. has received research grants from American Lung Association, Genentech, National Institutes of Health, Novartis, Patient‐Centered Outcomes Research Institute, Sanofi; consultancy fees from AstraZeneca, Boehringer Ingelheim, Genentech, Novartis, Regeneron; and speakers' bureau fees from Genentech, Sanofi. J.W. has received research grants from Aimmune, DBV Technologies, National Institute of Allergy and Infectious Diseases, Regeneron and is a consultant for ALK Abello, Jubilant HollisterStier. WWC has received speaker's fees from AstraZeneca, Boehringer Ingelheim, Regeneron, Sanofi, Teva, and consultancy fees from Aerocrine, Alcon Laboratories, AstraZeneca, Baxalta, Boehringer Ingelheim, Circassia, CSL Behring, Genentech, GlaxoSmithKline, Greer Laboratories, Grifols, Horizon Pharma, Kaleo, Meda, Mylan, Novartis, Pfizer, Regeneron, Sanofi, Shire, Teva, Valeant Pharmaceuticals. WGS has received research grants from National Institutes of Health, Aimmune/NestleAngany, Allergy Therapeutics, Celgene, Food Allergy Science Initiative, Genentech, Novartis, Regeneron; consultancy fees from Aimmune, Food Allergy Research & Education, Novartis; and royalties from UpToDate. R.A.W. has received research grants from Aimmune, DBV Technologies, Food Allergy Research & Education, Genentech, National Institutes of Health, Novartis, Regeneron, Siolta, and royalties from UpToDate. E.W. has received grant support from Aimmune, AnaptysBio, Astellas, Cour Pharma, Food Allergy Research & Education, Immune Tolerance Network, National Institute of Allergy and Infectious Disease, and research sponsorship from Regeneron. J.L., B.A., M.A.K., A.A., and A.R.R. are employees of, and may hold stock and/or stock options in, Regeneron Pharmaceuticals Inc. J.D.H. is an employee of, and may hold stock and/or stock options in, Regeneron Pharmaceuticals Inc. and has a patent pending (PCT/US2020/044958) with Regeneron Pharmaceuticals Inc. J.M.O. is an officer and employee at Regeneron Pharmaceuticals Inc., may hold stock and/or stock options, has a patent pending (PCT/US2020/0345843, PCT/US2022/0220211), and has issued patents (US patent numbers 10,392,439, 10,676,530, and 11,485,788). K.P., E.L., and L.P.M. are employees of, and may hold stock and/or stock options in, Sanofi. A.T.H. is an employee of, and may hold stock and/or stock options in, Regeneron Pharmaceuticals Inc. D.C.A. has received consultancy fees from Aimmune and has a patent pending (US 16/542,198; PCT/US2019/046706; US 16/721,805; PCT/US2019/067634). A.R. is an employee of, and may hold stock and/or stock options in, Aimmune.

Figures

FIGURE 1
FIGURE 1
Study design. DBPCFC, double‐blind, placebo‐controlled food challenge; exc, excluding; FAS, full analysis set; IDED, initial dose‐escalation day; inc, including; mFAS, modified full analysis set; OIT, oral immunotherapy; R, randomization. aPatients who switched from receiving dupilumab + OIT in the OIT up‐dosing period to receiving placebo + OIT in the OIT maintenance period are referred to as having “previous” treatment in the study objectives and endpoints. bPatients receiving the same study treatment in the OIT up‐dosing and OIT maintenance periods are referred to as having “continuous” treatment in the study objectives and endpoints.
FIGURE 2
FIGURE 2
Proportion of patients who passed a DBPCFC with 2044 mg (cumulative) of peanut protein after OIT up‐dosing, OIT maintenance, and post‐treatment safety follow‐up period in (A) the mFAS and (B) the FAS. DBPCFC, double‐blind, placebo‐controlled food challenge; FAS, full analysis set; mFAS, modified full analysis set; OIT, oral immunotherapy.
FIGURE 3
FIGURE 3
Change in cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC from baseline after (A) the OIT up‐dosing and OIT maintenance treatment periods in the mFAS and (B) the OIT up‐dosing and OIT maintenance treatment periods in the FAS. DBPCFC, double‐blind, placebo‐controlled food challenge; FAS, full analysis set; mFAS, modified full analysis set; OIT, oral immunotherapy.
FIGURE 4
FIGURE 4
Percentage change from baseline to end of study (weeks 64–76) in biomarkers (A) IgE, (B) ps‐IgE, (C) ps‐total IgG, (D) ps‐IgG4, (E) ps‐IgG4/ps‐IgE ratio, and (F) ps‐total IgG/ps‐IgE ratio (mFAS)a. Ig, immunoglobulin; mFAS, modified full analysis set; OIT, oral immunotherapy; ps, peanut‐specific. aDifference in week ranges for study visits is due to pooled mFAS and FAS data, where a 12‐week extension was granted due to COVID‐19 in the modified procedure.
FIGURE 5
FIGURE 5
Mean (±SD) concentrations of functional dupilumab serum by nominal time and treatment tier during (A) the pre‐OIT and OIT up‐dosing period, and (B) the OIT maintenance and post‐treatment follow‐up period (PAS). OIT, oral immunotherapy; PAS, pharmacokinetic analysis set; q2w, every 2 weeks.
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