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

Official title

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

Overview

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.

Interventions

• 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
• Other Allergenic food avoidance
  Allergenic food avoidance is the standard of care for patients allergic to food

Primary outcome measures

• 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 [Time frame: Month 19 of the study in the OIT-cohort and Month 24 in the NAT-cohort]

Secondary outcome measures (3)

• 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) [Time frame: 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 [Time frame: 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) [Time frame: End of study in OIT-cohort: Month 24]

Eligibility criteria

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.

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

Spain · 1 center

• Hospital Infantil Universitario Niño Jesús. Avenida de Menéndez Pelayo, número 65 — Madrid

Identifiers

NCT: NCT07419243 · R-0011/26

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗