Multi-Food Oral Immunotherapy for Peanut and Tree Nuts

NCT07764159 | Not Yet Recruiting DMC

• 1 other identifier: Multifood
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 4

Brief Summary

This study aims to evaluate the efficacy and safety of multi-food oral immunotherapy (multi-OIT) using peanut and tree nuts proteins in children with confirmed food allergy to at least two allergens. Participants will be randomized in a 2:1 ratio to receive either multi-OIT or standard management consisting of an elimination diet. The primary objective is to evaluate immunotherapy efficacy defined as achieving tolerance to a cumulative dose of 4444 mg of protein during an oral food challenge (OFC-2) for at least one allergen that elicited a reaction during baseline challenge (OFC-1), compared with the control group. Secondary outcomes include the proportion of participants tolerating multiple allergens at the target cumulative dose; the incidence, type, and severity of adverse events classified according to the World Allergy Organization (WAO) grading system; changes in immunological parameters, including allergen-specific IgE and IgG4 levels; changes in skin prick test responses; changes in the quality of life of patients and their families.

Conditions

Food Allergies; Food Allergy in Children; Peanut Allergies; Tree Nut Allergies; Oral Immunotherapy for Food Allergy

Outcome Measures

Primary Outcomes (1)

• Immunotherapy Efficacy

  Evaluation of immunotherapy efficacy defined as achieving tolerance to a cumulative dose of 4444 mg of protein during OFC-2 for at least one allergen that elicited a reaction during OFC-1, compared with the control group.

  Up to 21 months after starting oral immunotherapy

Secondary Outcomes (6)

• Proportion of Participants Tolerating at least 2, 3, 4 or 5 Allergens at a Cumulative Dose of 4444 mg During OFC-2

  Up to 21 months after starting oral immunotherapy

• Change in Maximum Tolerated Allergen Dose from OFC-1 to OFC-2

  Up to 21 months after starting oral immunotherapy

• Incidence, Type and Severity of Adverse Events During Immunotherapy Compared with Control (WAO Grading)

  Up to 21 months after starting oral immunotherapy

• Change in Skin Prick Test (SPT) Wheal Diameter for Peanut and Tree Nut Allergens from Baseline to Final Assessment

  Up to 21 months after starting oral immunotherapy

• Change from Baseline in Allergen-Specific IgE (sIgE) and IgG4 Levels

  Up to 21 months after starting oral immunotherapy

Study Arms (2)

Multi-Food Oral Immunotherapy (Multi-OIT)

EXPERIMENTAL

Participants will receive multi-food oral immunotherapy (multi-OIT) using a standardized mixture of peanut and tree nuts proteins (cashew, walnut, hazelnut, and almond). Treatment includes a dose-escalation phase (1-300 mg protein per allergen) followed by a maintenance phase for 12 months (+/- 3 months) with a target daily dose of 300 mg of protein per allergen. Dose increases will be performed under medical supervision, and daily dosing will be continued at home. The total treatment duration is approximately 18 months.

Other: Multi-Food Oral Immunotherapy (Multi-OIT) with Peanut and Tree Nuts Proteins

Standard of Care (Elimination Diet)

ACTIVE COMPARATOR

Participants will continue standard management consisting of strict elimination of peanut and tree nuts from the diet and use of rescue medications, including epinephrine, in case of accidental exposure. Participants will be monitored according to the study schedule and will undergo follow-up assessments comparable to the experimental group.

Other: Standard of Care (Elimination Diet)

Interventions

Multi-Food Oral Immunotherapy (Multi-OIT) with Peanut and Tree Nuts Proteins OTHER

Multi-food oral immunotherapy using a standardized mixture of peanut and tree nuts proteins (cashew, walnut, hazelnut, and almond), administered in a dose-escalation phase followed by a maintenance phase with a target daily dose of 300 mg of protein per allergen.

Multi-Food Oral Immunotherapy (Multi-OIT)

Standard of Care (Elimination Diet) OTHER

Standard management consisting of strict dietary avoidance of peanut and tree nuts, along with the use of rescue medications, including epinephrine, in the event of accidental allergen exposure.

Standard of Care (Elimination Diet)

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 1-12 years;
• Confirmed allergy to at least two allergens included in the protocol, i.e., peanut and/or tree nuts: cashew, walnut, hazelnut, and almond;
• Positive skin prick test (SPT) (wheal diameter ≥ 3 mm) and/or specific IgE (sIgE) level \> 0.35 kUA/L for at least two of the analyzed allergens;
• Positive OFC-1 (oral food challenge) of grade I-IV according to the WAO classification for at least two allergens, with a positive reaction occurring after administration of a dose ≥ 3 mg and ≤ 3000 mg of allergen protein;
• Participants may be enrolled based on the abbreviated procedure as outlined in the study description;
• Written informed consent obtained from a legal guardian, and, where applicable, assent from the child in accordance with their age and level of maturity;
• Good prognosis for compliance and cooperation of the patient and their caregivers.

You may not qualify if:

• Allergic reaction at the lowest challenge dose of 1 mg of allergen protein for any allergen, or no allergic reaction after administration of the maximum dose of 3000 mg of allergen protein for at least four of the analyzed allergens;
• History of anaphylaxis with a grade V reaction according to the WAO classification, either during an oral food challenge or in the patient's medical history;
• Severe asthma;
• Poorly controlled asthma according to GINA 2025 (lack of symptom control and/or ≥2 exacerbations requiring systemic glucocorticoids or ≥1 exacerbation requiring hospitalization within the last 12 months), or in children able to perform spirometry: FEV1 \< -1.64 Z-score and/or FEV1/FVC \< -1.64 Z-score;
• Eosinophilic gastrointestinal disease;
• Other chronic diseases requiring ongoing treatment which, in the investigator's opinion, may increase the risk associated with study participation or interfere with the interpretation of results, including severe cardiac disease, epilepsy, metabolic disorders, or diabetes;
• Previous immunotherapy with food allergens;
• Concurrent immunotherapy with aeroallergens;
• Treatment with biologic agents, beta-blockers, ACE inhibitors, or calcium channel blockers;
• Oral corticosteroid therapy meeting any of the following criteria: daily treatment for \>1 month within the last 12 months; at least two courses lasting ≥7 days within the last 12 months; one course lasting ≥7 days within the last 3 months;
• Lack of consent to participate in the study or insufficient cooperation of the patient and/or caregivers. In such cases, patients will receive standard medical care, including allergen avoidance and provision of emergency medication.

Sponsors & Collaborators

• Medical University of Warsaw: lead

Study Sites (4)

Department of Pediatric Pulmonology, Allergology and Clinical Immunology, Institute of Pediatrics, Karol Jonscher Clinical Hospital, Poznań University of Medical Sciences

Poznan, Greater Poland Voivodeship, 60-572, Poland

Location

Department of Pediatrics, Children's Diseases Clinic, Jagiellonian University Medical Colleg, Division of Pulmonology, Allergology and Dermatology, University Children's Hospital in Kraków

Krakow, Lesser Poland Voivodeship, 30-663, Poland

Location

Allergy Unit, Department of Pulmonary Diseases, Children's Hospital in Dziekanów Leśny

Dziekanów Leśny, Masovian Voivodeship, 05-092, Poland

Location

Department of Paediatric Pulmonology and Allergology, Medical University of Warsaw

Warsaw, Masovian Voivodeship, 02-091, Poland

Location

Related Publications (16)

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• Upton JEM, Toscano-Rivero D, Ke D, Berenjy A, Lejtenyi D, Beaudette L, Yin X, Li CH, Duan LY, Cohen CG, Kim V, Marzouk S, Grunebaum E, McCusker CT, Mazer B, Eiwegger T, Ben-Shoshan M. Peanut Oral Immunotherapy Using 30 and 300 mg Maintenance Doses. J Allergy Clin Immunol Pract. 2026 Jan;14(1):223-232.e7. doi: 10.1016/j.jaip.2025.10.007. Epub 2025 Oct 16.

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• Upton JEM, Li CH, Berenjy A, Galper A, Yin X, Celik A, Duan L, Wong S, Ditlof CM, San Diego KE, Hoang JA, Ben-Shoshan M, Kothari A, Hung L, Monteiro M, Phue WH, Moraes TJ, Eiwegger T. Safety and Efficacy of Very Low-Dose Multi-Nut Oral Immunotherapy in Children. Clin Transl Allergy. 2025 Dec;15(12):e70125. doi: 10.1002/clt2.70125.

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• Jones SM, Kim EH, Nadeau KC, Nowak-Wegrzyn A, Wood RA, Sampson HA, Scurlock AM, Chinthrajah S, Wang J, Pesek RD, Sindher SB, Kulis M, Johnson J, Spain K, Babineau DC, Chin H, Laurienzo-Panza J, Yan R, Larson D, Qin T, Whitehouse D, Sever ML, Sanda S, Plaut M, Wheatley LM, Burks AW; Immune Tolerance Network. Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study. Lancet. 2022 Jan 22;399(10322):359-371. doi: 10.1016/S0140-6736(21)02390-4.

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• Erdle SC, Cook VE, Cameron SB, Yeung J, Kapur S, McHenry M, Chan ES, Mak R, Rex GA, Wong T, Soller L. Real-World Safety Analysis of Preschool Tree Nut Oral Immunotherapy. J Allergy Clin Immunol Pract. 2023 Apr;11(4):1177-1183. doi: 10.1016/j.jaip.2023.01.031. Epub 2023 Feb 1.

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• Huang J, Puglisi LH, Cook KA, Kelso JM, Wangberg H. Safety and Feasibility of Peanut, Tree Nut, and Sesame Oral Immunotherapy in Infants and Toddlers in a Real-World Setting. J Allergy Clin Immunol Pract. 2025 Jan;13(1):185-191.e3. doi: 10.1016/j.jaip.2024.09.025. Epub 2024 Sep 30.

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MeSH Terms

Conditions

Food Hypersensitivity; Peanut Hypersensitivity; Nut Hypersensitivity

Interventions

Standard of Care; Elimination Diets

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Nut and Peanut Hypersensitivity

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Central Study Contacts

Katarzyna Grzela, PhD, MD

CONTACT

+48 22 3179417; katarzyna.grzela@wum.edu.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: August 13, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: August 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data requests may be submitted beginning 9 months after publication of the primary study results. Approved data will be made available for a period of up to 24 months. Requests for extension beyond this period will be considered on a case-by-case basis.
• Access Criteria: Access to de-identified individual participant data (IPD) may be requested by qualified researchers conducting independent scientific research. Access will be granted following review and approval of a research proposal and a corresponding Statistical Analysis Plan (SAP), and upon execution of a Data Sharing Agreement (DSA). For additional information or to submit a request, please contact katarzyna.grzela@wum.edu.pl

Locations

PL (4)