J Andrew Bird1, Jonathan M Spergel2, Stacie M Jones3, Rima Rachid4, Amal H Assa'ad5, Julie Wang6, Stephanie A Leonard7, Susan S Laubach8, Edwin H Kim9, Brian P Vickery10, Benjamin P Davis11, Jennifer Heimall2, Antonella Cianferoni2, Andrew J MacGinnitie4, Elena Crestani4, A Wesley Burks9. 1. Division of Allergy & Immunology, University of Texas Southwestern Medical Center, Dallas, Tex. Electronic address: drew.bird@utsouthwestern.edu. 2. Division of Allergy & Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa. 3. Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Ark. 4. Division of Allergy & Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass. 5. Division of Allergy & Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 6. Division of Allergy & Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY. 7. Department of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, Calif. 8. Department of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, Calif; Allergy and Asthma Medical Group and Research Center, San Diego, Calif. 9. Department of Pediatrics, University of North Carolina, Chapel Hill, NC. 10. Department of Pediatrics, University of North Carolina, Chapel Hill, NC; Department of Clinical Development, Aimmune Therapeutics, Brisbane, Calif. 11. Division of Immunology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
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, 26placebo) 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.
RCT Entities:
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.
Authors: Elissa M Abrams; Stephanie C Erdle; Scott B Cameron; Lianne Soller; Edmond S Chan Journal: Curr Allergy Asthma Rep Date: 2021-04-30 Impact factor: 4.806
Authors: R Sharon Chinthrajah; Natasha Purington; Sandra Andorf; Andrew Long; Katherine L O'Laughlin; Shu Chen Lyu; Monali Manohar; Scott D Boyd; Robert Tibshirani; Holden Maecker; Marshall Plaut; Kaori Mukai; Mindy Tsai; Manisha Desai; Stephen J Galli; Kari C Nadeau Journal: Lancet Date: 2019-09-12 Impact factor: 79.321