Sustained Unresponsiveness (SU) to Sesame Protein Following Low-dose Oral Allergen-specific Immunotherapy

Official title

Evaluation of the Acquisition of Sustained Unresponsiveness (SU) to Sesame Protein Following Low-dose Oral Immunotherapy - Long-term Follow-up of Patients From the RCT Efficacy and Safety of Low-dose Sesame Oral Immunotherapy in Pediatric Patients, NCT06261554.

Overview

This study is a long-term follow-up of participants from the randomized controlled trial (RCT) "Efficacy and Safety of Low-Dose Sesame Oral Immunotherapy in Pediatric Patients", NCT06261554. At the end of the original RCT all participants will undergo an open Oral Food Challenge (OFC) to assess desensitization after 3 months on the maintenance dose of OIT. Patients who have completed the first part of the study will be invited to the current part of the project: * First arm (initial experimental group) - patients will continue oral immunotherapy (OIT) with low dose of sesame protein (300mg) for the next 8 months (+/- 3 weeks). * Second arm (initial control group - one year on a sesame elimination diet) - patients will begin OIT following the protocol used in the first part of the study (RCT). Upon completion of this initial phase, they will continue immunotherapy for an additional 8 months (+/- 3 weeks). After an additional 8 months (+/- 3 weeks) of OIT, all study participants will undergo a 4-week cessation of treatment, followed by an open Oral Food Challenge (OFC) to assess the development of sustained unresponsiveness (SU).

Detailed description

Oral immunotherapy (OIT) is currently considered the most effective treatment for food allergies. The two primary goals of food immunotherapy are desensitization and sustained unresponsiveness.

Desensitization refers to the induction of temporary tolerance to the allergen, which is maintained only through regular, ongoing exposure. In contrast, the most desirable outcome-sustained unresponsiveness-is defined as the continued absence of allergic reactions to the allergen after discontinuation of immunotherapy for a specified period.

This study is a long-term follow-up of participants from the randomized controlled trial (RCT) "Efficacy and Safety of Low-Dose Sesame Oral Immunotherapy in Pediatric Patients", NCT06261554.

Patients who completed the initial phase will be invited to participate in the current phase of the project.

After 8 months (+/- 3 weeks) of continued OIT with a low dose of sesame protein, patients will be admitted for hospital-based assessments including skin prick testing, laboratory evaluations, and an open oral food challenge (OFC) to assess the acquisition of desensitization to sesame protein.

Patients who had a negative OFC (indicating confirmed desensitization) after 3 months of OIT during the initial phase of the study will proceed to the next part without undergoing another OFC prior to the treatment break. Only patients with confirmed desensitization, as evidenced by a negative OFC, will be eligible for the next phase.

Following a 4-week interruption in OIT, these patients will be invited for another Oral Food Challenge (OFC) to assess the acquisition of sustained unresponsiveness to sesame protein.

Patients with a positive OFC prior to the treatment break (i.e., those who did not achieve desensitization)-regardless of their original study group-will continue sesame OIT in accordance with the standard desensitization protocol used at the Clinic.

An interim analysis is planned after 50% of participants have completed the primary outcome assessment. The analysis will be conducted by an independent Data Monitoring Committee to evaluate safety and efficacy. Appropriate alpha-spending adjustments will be applied to control for Type I error.

Interventions

• Dietary supplement OIT with low dose sesame protein
  After 8 months of continued low-dose sesame OIT, patients will undergo hospital-based assessments, including skin prick testing, laboratory evaluations, and an open Oral Food Challenge (OFC) to evaluate desensitization. Patients who had a negative OFC after 3 months in the initial phase of the study-and thus confirmed desensitization-will skip the pre-break OFC and proceed directly to the next stage. Following a 4-week interruption in OIT, patients will return for a final hospital visit, durin

Primary outcome measures

• Sustained unresponsiveness determined by the outcome of the OFC [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]

Secondary outcome measures (12)

• Changes in sesame protein tolerance during OFC [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]
• Adverse event [Time frame: 11 months on the maintenance dose of OIT (±3 weeks) and a 4 week break (+/- 7 days).]
• Quality of life - FAQLQ (Food Allergy Quality of Life Questionnaire) [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]
• Basophil activation test (BAT) [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]
• Evaluation of Predictive Factors for the Acquisition of Sustained Unresponsiveness - wheal diameter in PTS [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]
• Evaluation of Predictive Factors for the Acquisition of Sustained Unresponsiveness - sIgE [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]
• Evaluation of Predictive Factors for the Acquisition of Sustained Unresponsiveness - IgG4 [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]
• Evaluation of Predictive Factors for the Acquisition of Sustained Unresponsiveness - the sIgE/tIgE ratio [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]
• Cut-off Values for Sustained Unresponsiveness Prediction - PTS wheal diameter [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]
• Cut-off Values for Sustained Unresponsiveness Prediction - sIgE [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]
• Determination of Threshold Differences Predictive of Sustained Unresponsiveness - PTS wheal diameter [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]
• Determination of Threshold Differences Predictive of Sustained Unresponsiveness - sIgE [Time frame: After 11 months on the maintenance dose of OIT (±3 weeks) and/or a 4-week break (±7 days).]

Eligibility criteria

Inclusion criteria

• Sesame allergy confirmed before starting immunotherapy
• Completion of the first part of the study - achieving the maintenance dose (300mg sesame protein) during immunotherapy
• Obtaining informed consent to participate in the study,
• Patient/carer cooperation.

Exclusion criteria

• Severe asthma,
• Mild/moderate poorly controlled asthma: FEV1<80% (under 5. percentile), FEV1/FVC<75% (under 5. percentile), hospitalisation for asthma exacerbation in the last 12 months,
• Oral/sublingual/subcutaneous immunotherapy against other allergens in the first year/season of immunotherapy
• Eosinophilic gastroenteritis,
• Severe, recurrent episodes of anaphylaxis within the last 6 months,
• Chronic diseases requiring ongoing treatment, including heart disease, epilepsy, metabolic diseases, diabetes,
• Taking medication:

• oral, daily steroid therapy >1 month in the past 12 months,
• At least two courses of oral steroid therapy (at least 7 days) within the last 12 months,
• One oral steroid therapy (min. 7 days) in the last 3 months,
• biological treatment,
• therapy with β-blockers, ACE-inhibitors, calcium channel inhibitors,
• Pregnancy,
• No consent to participate in the study,
• Lack of cooperation from the patient.

Well-controlled asthma, allergic rhinitis, atopic dermatitis are not considered exclusion criteria.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Poland · 1 center

• Medical University of Warsaw — Warsaw

Publications

• Cox LS, Sanchez-Borges M, Lockey RF. World Allergy Organization Systemic Allergic Reaction Grading System: Is a Modification Needed? J Allergy Clin Immunol Pract. 2017 Jan-Feb;5(1):58-62.e5. doi: 10.1016/j.jaip.2016.11.009. PMID 28065342
• Sampson HA, Gerth van Wijk R, Bindslev-Jensen C, Sicherer S, Teuber SS, Burks AW, Dubois AE, Beyer K, Eigenmann PA, Spergel JM, Werfel T, Chinchilli VM. Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol. 2012 Dec;130(6):1260-74. d PMID 23195525
• 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. PMID 30367908
• Shah A, Cox AL, Groetch M, Kattan JD, Schaible A, Sicherer SH, Tsuang A, Wang J, Oriel RC. Sesame oral immunotherapy outcomes in a pediatric cohort. J Allergy Clin Immunol Pract. 2025 Apr;13(4):938-940.e1. doi: 10.1016/j.jaip.2025.01.036. Epub 2025 Feb 8. No abstract available. PMID 39929303
• 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. PMID 29307409
• Pajno GB, Fernandez-Rivas M, Arasi S, Roberts G, Akdis CA, Alvaro-Lozano M, Beyer K, Bindslev-Jensen C, Burks W, Ebisawa M, Eigenmann P, Knol E, Nadeau KC, Poulsen LK, van Ree R, Santos AF, du Toit G, Dhami S, Nurmatov U, Boloh Y, Makela M, O'Mahony L, Papadopoulos N, Sackesen C, Agache I, Angier E, Halken S, Jutel M, Lau S, Pfaar O, Ryan D, Sturm G, Varga EM, van Wijk RG, Sheikh A, Muraro A; EAAC PMID 29205393
• Adatia A, Clarke AE, Yanishevsky Y, Ben-Shoshan M. Sesame allergy: current perspectives. J Asthma Allergy. 2017 Apr 27;10:141-151. doi: 10.2147/JAA.S113612. eCollection 2017. PMID 28490893
• Dalal I, Goldberg M, Katz Y. Sesame seed food allergy. Curr Allergy Asthma Rep. 2012 Aug;12(4):339-45. doi: 10.1007/s11882-012-0267-2. PMID 22610362

Identifiers

NCT: NCT07107451 · KB/60/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗