Induction of Sustained Unresponsiveness to Peanuts Using High- and Low-dose Peanut Oral Immunotherapy

Induction of Sustained Unresponsiveness to Peanuts Using High- and Low-dose Peanut Oral Immunotherapy - Evaluation of Efficacy and Safety

This study is a continuation of a clinical trial NCT044155930 comparing the efficacy and safety of oral immunotherapy (OIT) with low or high doses of peanut protein (150 or 300 mg, respectively) and will involve patients who have accomplished their per-protocol participation in that trial.

The aim of current study is to assess a sustained unresponsiveness (SU) to allergen protein after at least 8 months of previously assigned high- or low-dose peanut OIT, followed by 4-week-allergen avoidance, and verified by an open oral food challenge (OOFC).

Study Overview

• Status: Recruiting
• Conditions: Peanut Allergy
• Intervention / Treatment: Dietary supplement: High dose OIT; Dietary supplement: Low dose OIT

Detailed Description

Oral immunotherapy is considered the most effective food allergy treatment. There are two main goals of food immunotherapy: achievement of desensitisation and sustained unresponsiveness. Desensitization is a temporary state of clinical non-reactivity which requires regular intake of allergen, whereas sustained unresponsiveness is defined as lack of clinical reaction to a food allergen after discontinuing OIT for a specific period of time.

The study is a continuation of a clinical trial NCT044155930, which was designed to compare the efficacy and safety of oral immunotherapy (OIT) with low or high doses of peanut protein (150 or 300 mg, respectively) in children with a confirmed diagnosis of peanut allergy. The participants of current study will be recruited from patients who have accomplished their per-protocol participation in previous trial.

Patients will receive the same maintenance dose of peanut allergen, which was used in previous trial (150 or 300 mg, respectively), for at least 8 months (32 weeks +/-2 weeks). Then, OIT will be discontinued for 4 weeks with strict peanut avoidance. After this period, an open oral food challenge (OOFC) will be performed to assess the achievement of sustained unresponsiveness.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Magdalena Chojnowska-Wójtowicz, MD; Phone Number: 22-317-9431; Email: magdalena.chojnowska@uckwum.pl
• Study Contact Backup: Name: Katarzyna Grzela, MD, PhD; Phone Number: 22-317-9431; Email: katarzyna.grzela@wum.edu.pl

Study Locations

• Poland
  • Warsaw, Poland
    • Recruiting
    • Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw
    • Contact: Wioletta Zagórska, PhD, MD; Email: wiola.zagorska@gmail.com
    • Principal Investigator: Magdalena Chojnowska-Wójtowicz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 13 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients who have accomplished their per-protocol participation in trial NCT044155930.
• signed Informed Consent by parent/legal guardian and patient aged>16 years old
• patient's/caregiver's cooperation with researcher

Exclusion Criteria:

• severe asthma
• uncontrolled mild/moderate asthma: forced expiratory volume at one second (FEV1)<80% (under 5 percentile), FEV1/forced vital capacity (FEV)<75% (under 5 percentile), hospitalization due to asthma exacerbation within last 12 months
• current oral/sublingual/subcutaneous immunotherapy with another allergen
• eosinophilic esophagitis
• allergic reaction of 4th or higher grade according to the World Allergy Organisation Systemic Allergic Reaction Grading System during immunotherapy
• a history of severe recurrent anaphylaxis episodes
• chronic diseases requiring continous treatment, including heart disease, epilepsy, metabolic disease, diabetes

• medication:

  • oral, daily steroid therapy exceeding 1 month within the last 12 months
  • at least two courses of oral steroid therapy (at least 7 days) within the last 12 months
  • oral steroid therapy longer than 7 days within the last 3 months
  • biological treatment
  • the need to constantly take antihistamines
  • therapy with b-blockers, angiotensin converting enzyme (ACE) inhibitors, calcium channel inhibitors
• pregnancy
• no consent to participate in the study
• lack of patient cooperation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High dose; 20 patients	Dietary supplement: High dose OIT; Patients will receive daily a high dose of peanut flour (300 mg peanut protein) mixed with well-tolerated fruit mousse.
Active Comparator: Low dose; 20 patients	Dietary supplement: Low dose OIT; Patients will receive daily a low dose of peanut flour (150 mg peanut protein) mixed with well-tolerated fruit mousse.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained unresponsiveness to a peanut protein after discontinuing oral immunotherapy for 4 weeks.	The share of participants who tolerate a single dose of 150 mg or 300 mg of peanut protein (depending on the maintenance dose) at oral food challenge.	Up to 9 months after starting maintenance phase
The highest tolerated dose of peanut protein after discontinuing oral immunotherapy for 4 weeks.	Sustained unresponsiveness assessed as the highest tolerated dose of peanut protein at oral food challenge.	Up to 9 months after starting maintenance phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number and severity of adverse events during OIT treatment and at OOFC will be assessed and compared between both groups.	Up to 9 months after starting maintenance phase
Occurence of eosinophilic esophagitis.	Number and severity of eosinophilic esophagitis symptoms following OIT treatment assessed and compared between both groups.	Up to 9 months after starting maintenance phase
Laboratory data	Change in serum levels of specific immunoglobulin E (sIgE) to peanut components and peanut-specific immunoglobulin G4 (sIgE4) levels at different time points: at the start and at the end of oral immunotherapy, and after 4 weeks of allergen avoidance, assessed for each individual and compared between groups.	Up to 9 months after starting maintenance phase
Skin prick test (SPT)	Change in peanut skin prick test wheal in different time points: at the start, and at the end of oral immunotherapy, and after 4 weeks of allergen avoidance, assessed for each individual and compared between groups.	Up to 9 months after starting maintenance phase

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Investigators: Study Chair: Katarzyna Grzela, MD, PhD, Medical University of Warsaw

Publications and helpful links

General Publications

• Burks AW, Sampson HA, Plaut M, Lack G, Akdis CA. Treatment for food allergy. J Allergy Clin Immunol. 2018 Jan;141(1):1-9. doi: 10.1016/j.jaci.2017.11.004.
• Nagakura KI, Yanagida N, Sato S, Nishino M, Asaumi T, Ogura K, Ebisawa M. Low-dose oral immunotherapy for children with anaphylactic peanut allergy in Japan. Pediatr Allergy Immunol. 2018 Aug;29(5):512-518. doi: 10.1111/pai.12898. Epub 2018 May 10.
• Patrawala M, Shih J, Lee G, Vickery B. Peanut Oral Immunotherapy: a Current Perspective. Curr Allergy Asthma Rep. 2020 Apr 20;20(5):14. doi: 10.1007/s11882-020-00908-6.
• Rodriguez Del Rio P, Escudero C, Sanchez-Garcia S, Ibanez MD, Vickery BP. Evaluating primary end points in peanut immunotherapy clinical trials. J Allergy Clin Immunol. 2019 Feb;143(2):494-506. doi: 10.1016/j.jaci.2018.09.035. Epub 2018 Oct 24.
• PALISADE Group of Clinical Investigators; Vickery BP, Vereda A, Casale TB, Beyer K, du Toit G, Hourihane JO, Jones SM, Shreffler WG, Marcantonio A, Zawadzki R, Sher L, Carr WW, Fineman S, Greos L, Rachid R, Ibanez MD, Tilles S, Assa'ad AH, Nilsson C, Rupp N, Welch MJ, Sussman G, Chinthrajah S, Blumchen K, Sher E, Spergel JM, Leickly FE, Zielen S, Wang J, Sanders GM, Wood RA, Cheema A, Bindslev-Jensen C, Leonard S, Kachru R, Johnston DT, Hampel FC Jr, Kim EH, Anagnostou A, Pongracic JA, Ben-Shoshan M, Sharma HP, Stillerman A, Windom HH, Yang WH, Muraro A, Zubeldia JM, Sharma V, Dorsey MJ, Chong HJ, Ohayon J, Bird JA, Carr TF, Siri D, Fernandez-Rivas M, Jeong DK, Fleischer DM, Lieberman JA, Dubois AEJ, Tsoumani M, Ciaccio CE, Portnoy JM, Mansfield LE, Fritz SB, Lanser BJ, Matz J, Oude Elberink HNG, Varshney P, Dilly SG, Adelman DC, Burks AW. AR101 Oral Immunotherapy for Peanut Allergy. N Engl J Med. 2018 Nov 22;379(21):1991-2001. doi: 10.1056/NEJMoa1812856. Epub 2018 Nov 18.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2022
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 20, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 29, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: children; food allergy; peanut; sustained unresponsiveness
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Nut and Peanut Hypersensitivity; Peanut Hypersensitivity
• Other Study ID Numbers: Sustained unresponsiveness

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No