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

https://doi.org/10.1016/j.jaip.2017.09.016Get rights and content
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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.

Key words

AR101
ARC001
Desensitization
Double-blind placebo-controlled trial
Food allergy
Oral immunotherapy
OIT
Peanut allergy

Abbreviations used

AE
Adverse event
CI
Confidence interval
DBPCFC
Double-blind, placebo-controlled food challenge
EoE
Eosinophilic esophagitis
FDA
United States Food and Drug Administration
GI
Gastrointestinal
IQR
Interquartile range
ITT
Intent-to-treat
MTD
Maximum tolerated dose
OIT
Oral immunotherapy
ps-IgE
Peanut-specific IgE
SAE
Serious adverse event
SD
Standard deviation
SPT
Skin prick test
TEAE
Treatment-emergent AE

Cited by (0)

Aimmune Therapeutics, Inc. provided funding for this study. This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102), University of North Carolina Clinical and Translational Science Center, National Institutes of Health Award UL1TR001111, Icahn School of Medicine Clinical and Translational Science Center, National Institutes of Health Award UL1TR000067, The Children's Hospital of Philadelphia Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL1TR000003).

Conflicts of interest: J. A. Bird has received research and travel support from Aimmune Therapeutics; is on the Food Allergy Research and Education Clinical Advisory Board Executive Committee; has received consultancy fees from Aimmune Therapeutics (Global Advisory Board) and Wedbush Consulting; has received research support from DBV Technologies; has received lecture fees from DBV Technologies and Aimmune Therapeutics. J. M. Spergel has received research support from Aimmune, Food Allergy Research and Education (FARE), End Allergy Together, and National Institutes of Health (NIH); has received consultancy fees from DBV Technologies and Regeneron; has received lecture fees from Abbott and Medscape; receives royalties from UpToDate; and has stock/stock options in DBV Technologies. S. M. Jones has received research support from Aimmune, Food Allergy Research and Education, and DBV Technologies; is on the Aimmune Scientific Advisory Board; is on the Food Allergy Research and Education Research Advisory Board. R. Rachid has received research and travel support and consultancy fees from Aimmune Therapeutics. A. H. Assa'ad has received research and travel support, and consultancy fees from Aimmune; is a member of the American Academy of Allergy, Asthma & Immunology (AAAAI) Board of Directors (unpaid, but did receive travel support); is employed by Cincinnati Children's Hospital Medical Center; has received research support from DBV Technologies and Astellas; has received lecture fees and travel support from AAOA, Pittsburgh Allergy Society, Toledo Allergy Society, Intermountain Allergy Society, Southeastern Allergy Society, Michigan Allergy Society, Winthrop University, Akron University, Egyptian Allergy Society, AAAAI, American College of Allergy, Asthma & Immunology (ACAAI), and World Allergy Organization (WAO). J. Wang has received research and travel support as well as consultancy and lecture fees from Aimmune; and receives royalties from UpToDate. S. A. Leonard has received research support from Aimmune Therapeutics, FARE, and DBV Technologies; is on the FARE Medical Advisory Board; has received lecture fees from University of California, San Diego. S. S. Laubach has received research support from Aimmune; and has received travel support from Food Allergy Research and Education. E. H. Kim has received consultancy fees from Aimmune Therapeutics and DBV Technologies; has received travel support from Aimmune Therapeutics; has received consultancy fees from HC Wainwright; has received research support from NIH and FARE; and has received lecture fees from the Eastern Allergy Conference. B. P. Vickery has received research support from, is employed by, and has stock/stock options in Aimmune Therapeutics. A. Cianferoni has received research support from Aimmune and DBV; has received lecture fees from DBV. A. J. MacGinnitie has received research support from Aimmune and DBV Technologies. A. W. Burks is an NIH Hypersensitivity, Autoimmune, and Immune-mediated Diseases study section member; is a member of the NIH Allergy, Immunology, and Transplantation Research Committee review panel; is a limited minority shareholder in Allertein; receives royalties from the American Society for Microbiology and Elsevier; was on the FARE advisory board; is a member of the World Allergy Organization board; has received research support from FARE, NIH, and Wallace Research Foundation; has received consultancy fees from Adept Field Solutions, Aimmune Therapeutics, Astellas Pharma Global Development, Biomerica, Evelo Biosciences/Epiva Biosciences, First Manhattan Co, Genentech, GLG Research, Insys Therapeutics, Intrommune Therapeutics, PPD Development, Regeneron, Sanofi US Services, SRA International, Stallergenes, UKKO, Inc., and Valeant Pharmaceuticals North America; and is on the Aimmune Therapeutics advisory board. The rest of the authors declare that they have no relevant conflicts of interest.