Oral Immunotherapy for Young Children With Peanut Allergy - Small Children OIT (SmaChO)

Oral Immunotherapy for Young Children With Peanut Allergy - Small Children OIT (SmaChO)

Open label study with peanut oral immunotherapy (OIT). Peanut allergic children aged 1-3 years of age will be randomized 2:1 to:

1. Peanut OIT with slow up-dosing (40-60 weeks) up to a maintenance dose of 285 mg daily oral peanut protein or
2. Control group with peanut allergic children who do not undergo OIT.
3. In addition, a group of healthy children without allergic diseases will be included in the study.

The primary outcome is tolerance to at least 750 mg peanut protein at a challenge after 3 years and sustained unresponsiveness (i.e. tolerance) to 750 mg peanut protein after 3 years of OIT followed by 4 weeks of avoidance.

Efficacy and safety will be compared between group 1 and 2. Group 3 is a control group for analyses of immunological markers.

Study Overview

• Status: Active, not recruiting
• Conditions: Peanut Allergy
• Intervention / Treatment: Dietary supplement: Peanut (bamba)

Detailed Description

Problem: Today there is no clinically available treatment for peanut allergy. Oral Immunotherapy (OIT) studies have shown promising results, particularly in younger children (<4 years).

Intervention: Peanut OIT in children aged 1-3 years with peanut allergy (clinical symptoms at peanut challenge and IgE >0.1 kU /l to peanut and/or Ara h 2).

Comparison: Three groups are compared. Peanut allergic children are randomized 2:1 to group 1 (active OIT) or group 2 (control). Group 3 consists of age-matched healthy controls:

Group 1; Children with peanut allergy receiving peanut OIT, slow up-dosing, 40-60 weeks, until the maintenance dose 285 mg peanut protein. Three years' treatment. (n=50 patients)

Group 2; Age-matched children with peanut allergy who do not undergo OIT peanut. Peanut challenge one and three years after inclusion. (n=25 patients)

Group 3; Healthy, non-allergic, age-matched children. No challenges are performed in this group. (n=30 patients)

Group 4; Children not reacting at the baseline peanut challenge (n=X patients)

Inclusion of study subjects: A review of samples sent to the Karolinska University Laboratory for IgE-ab responses to peanut/Ara h 2 for children in the Stockholm area aged 1-3 years is used for identification of potential participants to whom a letter is sent with information about the study. The families are randomized 2:1 to OIT or control group, group 1 or group 2.

Children without allergies, healthy Controls (group 3), will be identified through the day surgery at Astrid Lindgren's Children's Hospital.

If children are included in the study but they do not not react at the baseline peanutchallenge, they will not have any intervention (are not eligible to randomisation) and will have a follow-up after 1+3 years (without peanut challenges), group 4.

Outcomes: The primary outcome is defined as sustained unresponsiveness to 750 mg peanut protein (cumulative dose) at an open oral peanut challenge after 3 years of OIT+4 weeks of avoidance (group 1 and 2).

Secondary outcomes are adverse events among peanut allergic children with/without OIT treatment (group 1 and 2), and changes in quality of life parameters and immunological markers (group, 1, 2, 3).

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carina Uhl; Phone Number: 0725-993782; Email: smacho.sodersjukhuset@regionstockholm.se

Study Locations

• Sweden
  • Stockholm, Sweden
    • Forskningsenheten Södersjukhuset AB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children 1 - 3 years old at inclusion
• Positive baseline challenge at a maximum of the 250 mg peanut protein-dose with at least one objective symptom, or positive peanut challenge performed in the clinic in a similar way within 1 year from study start.
• IgE-ab to peanut and/or Ara h 2 ≥0.1 kUA/l, analyzed within 12 months from start of study
• Written consent for participation in the study from both Guardians

Exclusion Criteria:

• Other serious illness
• Previously life-threatening anaphylaxis (intensive care), regardless of the triggering agent
• A history of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, severe chronic gastroesophageal reflux disease (GERD), symptoms of dysphagia, unclear recurrent GI disorders
• Participation in another intervention study, if included in intervention Group
• Severe uncontrolled asthma
• Ongoing medication with biological drugs or oral steroids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: OIT peanut; Children with peanut allergy receiving peanut OIT. Peanut challenge are done before randomization and one and three years after inclusion. n=50 patients	Dietary supplement: Peanut (bamba); OIT peanut with slow-updosing for 40-60 weeks followed by maintenance. 3 years treatment.
No Intervention: Peanut avoidance; Children with peanut allergy not undergoing OIT peanut. Peanut challenge are done Before randomization and one and three years after inclusion. n=25 patients
No Intervention: Healthy controls; Control Group with non-allergic, age-matched children. No challenges are performed in this group. n=30 patients
No Intervention: Children not reacting at the baseline peanut challenge; Peanut-allergic children not reacting at the baseline peanut challenge, will not be eligible for randomisation. They will have a clinical visit after 1+3 years. No more challenges in this group. n=X patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained unresponsiveness to 750 mg peanut protein	Sustained unresponsiveness to 750 mg peanut protein (cumulative dose) at a peanut challenge after 3 years of OIT and 4 weeks of peanut avoidance. Measured at a peanut challenge	3 years and 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events during OIT treatment	Adverse events among peanut allergic children with OIT treatment	3 years
Quality of Life Before, during and after OIT peanut	Examine how quality of life, measured with Food Allergy Quality of Life Questionnaire-parental Form (FAQLQ-PF), is affected in families with peanut allergic children undergoing peanut OIT compared to those without peanut OIT. FAQLQ-PF has questions for food-allergy specific QoL with general emotional impact; food anxiety; social and dietary limitations. The FAQLQ-PF has a seven-point scale ranging from 0 (no impact on HRQL) to 6 (extreme impact on HRQL).Overall and domain-specific HRQL scores will be calculated. Higher scores mean a worse outcome and a score of ≥ ±0.5 will be considered clinically relevant.	3 years
Intestinal microbiome	The gut microbiome will be investigated with sequencing-based methods to monitor possible changes in the gut microbiota composition and function related to OIT treatment. This will be compared to samples from the non-allergic individuals (reference).	3 years
Immunological biomarkers	To study differerent immunological biomarkers (e.g. T-helper cell-population and polarization and IgE levels) before, during and after OIT treatment and compare this to healthy controls. Immunological marker in mononuclear cells in peripheral blood will be analyzed ex vivo with flowcytometri and RNA-sequensingplatforms. Cirkulating immunological factors, e.g. cytokines and chemocines will be analyzed in plasma with ELISA-based methods.Mononuclear cellpopulations in periferal blood will be exposed to different stimuli (such as peanut, anti-C D3/C D28) in vitro, type anf level of reaction in the different cellpopulations will be monitored at mRNA- och protein-level.	3 years
Tolerance to peanut protein at a challenge after 3 years	Is OIT peanut with a low dose and slow up dosing strategy in young peanut allergic Children safe and effective? Measured at a peanut challenge	3 years
Tolerance to peanut protein at a challenge after 1 year	Is OIT peanut with a low dose and slow up dosing strategy in young peanut allergic children safe and effective? Measured at a peanut challenge	1 year

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Investigators: Principal Investigator: Anna Asarnoj, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (Actual): August 13, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; Arachis; Peanut Hypersensitivity; Child preschool
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Peanut Hypersensitivity
• Other Study ID Numbers: 2019-04645

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