Oral Immunotherapy in Young Children With Food Allergy (ORKA-NL)

A Randomized Controlled Trial to Investigate the (Cost)Effectiveness of Oral Immunotherapy With Different Allergens in Young Children With an Established Food Allergy

The goal of this clinical trial is to learn about oral immunotherapy in food allergic children < 30 months of age. The main question it aims to answer is: What is the clinical- and cost-effectiveness of early low-dose oral immunotherapy aimed at long-term tolerance induction. Participants will receive oral immunotherapy for 1 year with a maintenance dose of 300 mg allergenic protein and are compared with food allergic infants not receiving oral immunotherapy to compare with natural tolerance development.

Study Overview

• Status: Enrolling by invitation
• Conditions: Food Allergy
• Intervention / Treatment: Dietary supplement: oral immunotherapy

Detailed Description

Primary objective: What is the clinical- and cost-effectiveness of early low-dose oral immunotherapy aimed at long-term tolerance induction in children under the age of 30 months with an established food allergy compared to routine care? Secondary objective: What is the effect of early low-dose oral immunotherapy in children under the age of 30 months with an established food allergy on (allergy specific) quality of life of parents and children compared to routine care? Study design: randomized controlled superiority trial Study population: Children between 9 and 30 months old with an IgE-mediated food allergy to peanut, tree nuts, cow's milk and/or hen's egg as proven by an oral food challenge. Intervention: 1-year low-dose oral immunotherapy (daily 300 mg allergenic protein) compared to strict avoidance in the control group.

Main study parameters/endpoints: Long-term tolerance as assessed by an exit oral food challenge at 4 weeks after discontinuation of the oral immunotherapy, combined with uncomplicated consumption of a full dose of the specific food at 6 months after discontinuation of the therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC, location AMC
  • Delft, Netherlands
    • Reinier de Graaf Gasthuis
  • Groningen, Netherlands
    • Martini Hospital
  • Overijssel
    • Deventer, Overijssel, Netherlands, 7416SE
      • Deventer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• An IgE-mediated food allergy to peanut, cashew, hazelnut, walnut, cow's milk and/or hen's egg as proven by sensitization to the specific allergen (sIgE > 0.35kU/l) and a positive oral food challenge.
• The fore-mentioned allergens are introduced into the diet of the child (the child is tolerant for the specific allergen(s)), or the child is diagnosed with a food allergy for the specific allergen(s).

Exclusion Criteria:

• (Suspected) eosinophilic oesophagitis
• Uncontrolled asthma/ viral wheeze.
• The inability of parents to follow instructions, recognize allergic reactions or administer emergency medication.
• Participation in any other intervention study at the time of the OIT study, with the exception of studies on guided early introduction of highly allergenic foods.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral immunotherapy; oral immunotherapy, maintenance phase with daily 300 mg allergenic protein during 1 year	Dietary supplement: oral immunotherapy; oral immunotherapy is performed by freely available, widely used food products, regularly part of a normal infant's diet such as peanut butter or boiled egg.
No Intervention: routine care; strictly avoidance of the specific allergenic food

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with sustained unresponsiveness to consumption of a specific allergenic food 4 weeks after stopping the 1-year oral immunotherapy (OIT)	Definition of sustained unresponsiveness: a participant who passed an oral food challenge (OFC) to 4.2 gram of the allergenic protein. Definition of the allergenic protein: the allergenic protein which induced an allergic response at an OFC at the start of the study, and was administered to the patient during the OIT (i.e. milk, egg, peanut, hazelnut, cashew or walnut).	Timing of the OFC: week 57 (52 weeks of OIT, followed by a 4-week allergenic food-free interval)
Percentage of tolerant participants at week 78	In children achieving sustained unresponsiveness (outcome 1), the allergen is introduced into the diet by parents at a regular base. Six months after discontinuation of the OIT, tolerance to the specific allergenic protein is assessed. Definition of tolerant: Percentage of children with uncomplicated (i.e. without any allergic symptoms) consumption at home of a full dose of the specific allergenic protein (e.g. a glass of milk or a sandwich with peanut butter).	week 78 = 6 months after stop of the 1-year oral immunotherapy
Cost-effectiveness ratio at 18 months (week 78).	Incremental cost-effectiveness ratio (ICER) at 18 months (week 78). Costs associated with oral immunotherapy will be measured in Euros. Effectiveness will be considered as percentage of tolerant participants at week 78.	18 months (week 78).
Cost-utility ratio at 18 months (week 78).	Incremental cost-utility ratio (ICUR) will be calculated for both groups using health-related quality of life (HRQoL) scores from the AQoL-6D (assessment of quality of life - 6 dimensions) and converted to utility scores and will be expressed in euros per QALY.	18 months (week 78): at the end of the study period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health related quality of life of children, during the 1-year OIT and six months after the therapy (week 78)	Children's quality of life as measured by: - Food Allergy Quality of Life Questionnaire - parental form (FAQLQ-PF) This questionnaire consists of 14 questions to be answered on a 7-point Likert-scale. Minimum score is 0 points (no impact of food allergy on quality of life), maximum score is 84 (high impact of food allergy on quality of life)	during oral immunotherapy (T=0, 26 weeks and 52 weeks), and 6 months after stopping the oral immunotherapy (78 weeks)
Occurrence of Adverse Event(s) Related to Oral Immunotherapy up to 65 weeks study participation	(Serious) adverse events related to oral immunotherapy	during build-up (up to 3 months) and 1-year oral immunotherapy, total 65 weeks
Levels of allergy-related immune parameters	Levels of allergen specific IgE and IgG4	at start of the therapy and after 6 and 12 months maintenance therapy
adherence	Rate of daily providing the oral immunotherapy	during 1 year oral immunotherapy
Health related quality of life of parents, during the 1-year OIT and six months after the therapy (week 78)	Parental quality of life as measured by: - Food Allergy Quality of Life- Parental Burden (FAQL-PB) This questionnaire consists of 17 questions to be answered on a 7-point Likert-scale. Minimum score is 0 points (no parental burden), maximum score is 102 (severe parental burden)	during oral immunotherapy (T=0, 26 weeks and 52 weeks), and 6 months after stopping the oral immunotherapy (78 weeks)

Collaborators and Investigators

• Sponsor: Deventer Ziekenhuis
• Collaborators: Utrecht University; University of Twente; Dutch National Health Care Institute
• Investigators: Principal Investigator: Ted Klok, MD PhD, Deventer Ziekenhuis

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Anticipated): December 30, 2024
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: December 20, 2022
• First Submitted That Met QC Criteria: February 11, 2023
• First Posted (Estimate): February 22, 2023

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: February 11, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: infants; food allergy; Oral immunotherapy
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity
• Other Study ID Numbers: NL81774.075.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data collected for this study will be stored in SPSS and Excel and analyzed in SPSS.

Access to trial IPD can be requested after the study is completed by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact wetenschapsbureau@dz.nl

• IPD Sharing Time Frame: 01-07-2025 - 01-07-2026
• IPD Sharing Access Criteria: Researchers wanting to use the data would have to contact the PIs with a research proposal and Statistical Analysis Plan (SAP).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No