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

J. Andrew Bird, Jonathan M. Spergel, Stacie M. Jones, Rima Rachid, Amal H. Assa'ad, Julie Wang, Stephanie A. Leonard, Susan S. Laubach, Edwin H. Kim, Brian P. Vickery, Benjamin P. Davis, Jennifer Heimall, Antonella Cianferoni, Andrew J. MacGinnitie, Elena Crestani, A. Wesley Burks

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology: In Practice
DOIs
StateAccepted/In press - Jan 1 2017

Fingerprint

Peanut Hypersensitivity
Immunotherapy
Placebos
Clinical Trials
Safety
Food
Intention to Treat Analysis
Humoral Immunity
Arachis
Biological Products
Cellular Immunity
Young Adult
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy : Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial. / Bird, J. Andrew; Spergel, Jonathan M.; Jones, Stacie M.; Rachid, Rima; Assa'ad, Amal H.; Wang, Julie; Leonard, Stephanie A.; Laubach, Susan S.; Kim, Edwin H.; Vickery, Brian P.; Davis, Benjamin P.; Heimall, Jennifer; Cianferoni, Antonella; MacGinnitie, Andrew J.; Crestani, Elena; Burks, A. Wesley.

In: Journal of Allergy and Clinical Immunology: In Practice, 01.01.2017.

Research output: Contribution to journalArticle

Bird, JA, Spergel, JM, Jones, SM, Rachid, R, Assa'ad, AH, Wang, J, Leonard, SA, Laubach, SS, Kim, EH, Vickery, BP, Davis, BP, Heimall, J, Cianferoni, A, MacGinnitie, AJ, Crestani, E & Burks, AW 2017, 'Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy: Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial', Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2017.09.016
Bird, J. Andrew ; Spergel, Jonathan M. ; Jones, Stacie M. ; Rachid, Rima ; Assa'ad, Amal H. ; Wang, Julie ; Leonard, Stephanie A. ; Laubach, Susan S. ; Kim, Edwin H. ; Vickery, Brian P. ; Davis, Benjamin P. ; Heimall, Jennifer ; Cianferoni, Antonella ; MacGinnitie, Andrew J. ; Crestani, Elena ; Burks, A. Wesley. / Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy : Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial. In: Journal of Allergy and Clinical Immunology: In Practice. 2017.
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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.",
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T1 - Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy

T2 - Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial

AU - Bird, J. Andrew

AU - Spergel, Jonathan M.

AU - Jones, Stacie M.

AU - Rachid, Rima

AU - Assa'ad, Amal H.

AU - Wang, Julie

AU - Leonard, Stephanie A.

AU - Laubach, Susan S.

AU - Kim, Edwin H.

AU - Vickery, Brian P.

AU - Davis, Benjamin P.

AU - Heimall, Jennifer

AU - Cianferoni, Antonella

AU - MacGinnitie, Andrew J.

AU - Crestani, Elena

AU - Burks, A. Wesley

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Desensitization

KW - Double-blind placebo-controlled trial

KW - Food allergy

KW - OIT

KW - Oral immunotherapy

KW - Peanut allergy

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