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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Peanut Allergy

Intervention / Treatment
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* Dietary Supplement: High dose OIT
* Dietary Supplement: Low dose OIT


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peanut, food allergy, sustained unresponsiveness, children