An Open-Label, Multicenter, Randomized Clinical Trial Evaluating the Efficacy and Safety of Oral Multi-Food Immunotherapy With Peanut and Tree Nuts Protein Mixtures
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 39
- Locations
- 4
- Primary Endpoint
- Immunotherapy Efficacy
Study Overview
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.
Detailed Description
This is an interventional, open-label, multicenter, randomized clinical trial enrolling 39 children aged 1-12 years with confirmed allergy to at least two of the following allergens: peanut, cashew, walnut, hazelnut and almond.
Participants will be randomized in a 2:1 ratio to either the experimental group receiving multi-food oral immunotherapy (multi-OIT) or the control group receiving standard of care consisting of an elimination diet and rescue medications. Multi-OIT will be administered using a standardized mixture of peanut and tree nuts proteins, with a dose-escalation phase followed by a maintenance phase targeting 300 mg of protein per allergen per day. Treatment duration will be approximately 18 months.
All participants will undergo oral food challenges at baseline (OFC-1) and at the end of the study (OFC-2). The primary efficacy endpoint is defined as the proportion of participants 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. Safety will be monitored throughout the study based on adverse events recorded in symptom diaries and classified according to established grading systems.
Secondary outcomes include the proportion of participants tolerating multiple allergens at the target cumulative dose, the frequency 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), skin prick test responses and quality of life of patients and their families.
Participants in the control group will be offered the option to receive immunotherapy after completion of the study.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to 12 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
- •Well-controlled asthma, allergic rhinitis, and atopic dermatitis are not exclusion criteria.
Arms & Interventions
Multi-Food Oral Immunotherapy (Multi-OIT)
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.
Intervention: Multi-Food Oral Immunotherapy (Multi-OIT) with Peanut and Tree Nuts Proteins (Other)
Standard of Care (Elimination Diet)
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.
Intervention: Standard of Care (Elimination Diet) (Other)
Outcomes
Primary Outcomes
Immunotherapy Efficacy
Time Frame: Up to 21 months after starting oral immunotherapy
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.
Secondary Outcomes
- 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)
- Change in Food Allergy-Related Quality of Life (FAQLQ)(Up to 21 months after starting oral immunotherapy)