Tolerance Results and Immune Mechanisms in Cow´s Milk and/or Hen´s Egg Allergic Children Following Natural Evolution or Oral Immunotherapy (alerITO)

Identification of Mechanisms and Biomarkers Predictive of Tolerance in Children With Food Allergies: Comparison Between Treatment With Oral Immunotherapy and Natural Evolution. alerITO Study

Allergy to Cow's milk and hen´s egg proteins are the most common causes of food allergies in early childhood and are associated with the occurrence of adverse events that may be life-threatening, quality of life impairment and negative nutritional and health economic impact.

However, contrarily to other food allergy models such as nuts/peanut allergy, milk and egg allergy have greater chances of natural resolution. While around 50% of children may outgrow milk or egg allergy by the age of 5 years old, only 22% of peanut allergic children at the age of 4 years can tolerate this food. However, it is also documented that, at 14 years of age, the persistence of milk and egg allergy still affects around 30% of these children.

Standard of care relies on food avoidance and treatment of accidental reactions, but this approach is unsatisfactory because adverse events and quality of life limitations still remain. Milk and egg Oral Immunotherapy (OIT) is the most promising therapeutic alternative and showed good results to induce Desensitization (ability to tolerate the food while it is regularly taken) but insufficient efficacy to achieve Sustained Unresponsiveness (SU) (ability to tolerate the food after a period of avoidance).

In the day-to-day practice, families and allergists of milk and egg allergic children frequently face the following dilemma: what is the best approach? Keep waiting for natural resolution or embarking in OIT? At the moment, there are only very limited data to guide this decision, specially in children with mild to moderate allergy, that still after 6 years of age withhold relevant chances of naturally outgrowing their allergy.

Our objective is conducting a longitudinal cohort-study of children undergoing food avoidance and children undergoing OIT to assess biomarkers of natural allergy resolution/persistence and OIT Desensitization/Sustained Unresponsiveness trajectories.

Study Overview

• Status: Recruiting
• Conditions: Food Allergy in Children
• Intervention / Treatment: Other: Allergenic food avoidance; Biological: Oral Immunotherapy

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pablo Rodríguez del Río, MD PhD; Phone Number: +34915035900; Email: prrio@yahoo.es

Study Locations

• Spain
  • Madrid
    • Madrid, Madrid, Spain, 28009
      • Recruiting
      • Hospital Infantil Universitario Niño Jesús. Avenida de Menéndez Pelayo, número 65
      • Contact: Pablo Rodríguez del Río, MD PhD; Phone Number: +34915035900; Email: prodriguezd@salud.madrid.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

NAT-cohort:

• Cow´s Milk and/or Hen´s Egg allergic patients 4 to 10 years old
• sIgE levels to milk OR egg extracts between 0.35 to 35kUA/L
• Positive entry Open food challenge with milk/egg with oFASS5 classification ≥2 with a maximum cumulative dose of up to 4193.7 mg of milk protein or 3110.8 mg of egg white protein
• Having a mild to moderate food allergy severity per the Definition of Food Allergy Severity (DEFASE) score (<13 points)
• Having signed the informed consent

OIT-cohort:

• Patients in the compITO study (NCT06976775) who are undergoing OIT and have achieved full desensitization to the food by month 7 of the study (end of study)
• Patients in the compITO study who are undergoing OIT and have achieved partial desensitization (tolerating a dose lower than the total dose, and a minimum of 3 doses above the entry challenge threshold) to the food by month 7 of the study (end of study)
• Having signed the informed consent

Exclusion Criteria:

NAT-cohort:

• Positive reaction in the entry open oral food challenge with a baseline Eliciting Dose (ED) 20 below the target ED20 for food. For milk, 23.1 mg (35.7 mg cumulative) of protein, or for egg, 19.5 mg (29.4 mg cumulative) of protein.
• Patient desire or medical indication to initiate OIT at any time within 29 months of study entry.
• No allergic reaction greater than oFASS5 grade 1 in the baseline challenge for the maximum cumulative programmed doses of 4193.7 mg of milk protein, or 3110.8 mg of egg white protein.
• Immunological diseases, immunomodulatory/blocking therapies.
• Severe atopic dermatitis according to the SCORing Atopic Dermatitis (SCORAD) classification
• Severe allergy, according to a DEFASE score ≥13
• Spirometry values with moderate-to-severe airflow obstruction (FEV1 <70%)
• Poorly controlled asthma according to clinical criteria
• Previous OIT for another food
• Within the first 3 months of treatment with Subcutaneous Aeroallergen Immunotherapy
• Within the first week of treatment with Sublingual Aeroallergen Immunotherapy
• Presence or suspicion of Eosinophilic Esophagitis
• Non-IgE-mediated allergy to milk or egg
• Pregnancy
• Significant medical comorbidities (renal, hepatic, or cardiac insufficiency, active infectious diseases, previous or concurrent cancers)
• Inability to provide informed consent
• Communication or cognitive barriers that prevent adherence to the protocol

OIT-cohort:

• Patients enrolled in the compITO study who have failed or withdrawn from the study for any reason.
• Patients with uncontrolled Atopic Dermatitis or Asthma at the time of enrolment, or who have developed Eosinophilic Esophagitis.
• Patients with confirmed pregnancy at the time of enrolment.
• Patients who have developed significant medical comorbidities (renal, hepatic, or cardiac insufficiency, active infectious diseases, previous or concurrent cancers) at the time of enrolment.
• Inability to provide informed consent.
• Communication or cognitive barriers that prevent adherence to the protocol.

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
Other: NAT-cohort; Cow´s milk or Hen´s egg allergic children following standard of care: allergenic food avoidance	Other: Allergenic food avoidance; Allergenic food avoidance is the standard of care for patients allergic to food
Active Comparator: OIT-cohort; Cow´s milk or Hen´s egg allergic children undergoing OIT to cow´s milk or Hen´s egg respectively	Biological: Oral Immunotherapy; OIT is a treatment where incremental doses of a food causing allergy to a patient are given until a target maintenance dose is reached, to increase his/her reactivity threshold

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of the proportion of patients achieving SU in the OIT-cohort after 2 years of OIT treatment vs the proportion of patients achieving natural resolution after 2 years of follow up	Month 19 of the study in the OIT-cohort and Month 24 in the NAT-cohort

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of the median Food Allergy Quality of Life Questionnaire, Parental Form (FAQLQ-PF) score change in patients in the OIT-cohort vs NAT-cohort between baseline and end of study (month 24 for OIT cohort, month 29 for the NAT cohort)	End of study in OIT-cohort: Month 24; End of study in NAT-cohort: Month 29
Number of adverse events with an ordinal Food Allergy Severity Score 5 (oFASS5) ≥2 reported until the end of study in both cohorts, NAT vs ITO	End of study in OIT-cohort: Month 24; End of study in NAT-cohort: Month 29
Comparison of the median burden of treatment score in the OIT-cohort at the end of study (24 months)	End of study in OIT-cohort: Month 24

Collaborators and Investigators

• Sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Collaborators: Fundación para la investigación biomética Hospital Infantil Universitario Niño Jesús

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2026
• Primary Completion (Estimated): December 30, 2029
• Study Completion (Estimated): July 30, 2030

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 16, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Quality of Life; Children; Microbiota; Biomarkers; Desensitization; Food allergy; OIT; Oral immunotherapy; Burden of treatment; Hen´s egg allergy; Cow´s milk allergy; Sustained Unresponsiveness; Natural evolution; FAQLQ
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity; Therapeutics; Biological Therapy; Immunomodulation; Immunotherapy
• Other Study ID Numbers: R-0011/26

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