Food Allergy in ChildrenSAFARINCT07825662
A Randomized Controlled Trial of Oral Immunotherapy Versus Allergen Avoidance in Children Under 2 Years With Food Allergy
A study testing Oral immunotheraphy (OIT) in people with Food Allergy in Children and Oral Immunotherapy for Food Allergy, run by Copenhagen Studies on Asthma in Childhood at 1 site in Denmark.
Trial summary
The goal of this clinical trial is to learn whether oral immunotherapy (OIT) is safe and effective for treating food allergy in children aged 0-2 years with peanut, tree nut, or sesame allergy. Read more about this study
- Who is it for?
- Ages Up to 24 months
- Conditions the study is for
- Food Allergy in Children, Oral Immunotherapy for Food Allergy
- What is being tested?
- Oral immunotheraphy (OIT)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteDenmark
- Study dates
- Sep 2026to Jun 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children age 0-2 years
- Diagnosed IgE-mediated food allergy to tree-nuts, sesame, and/or peanuts, defined as: Positive oral food challenge (OFC) at inclusion or within 6 months before AND positive SPT (≥ 3 mm) or specific IgE (≥ 0.35 kUA/L)
- Both parents provide informed consent
Who cannot join
- Already undergoing any form of immunotherapy
- Already undergoing any form of biological treatment
- Medical conditions precluding OITs: Uncontrolled asthma, atopic dermatitis requiring systemic therapy, eosinophilic esophagitis (EoE) and other GI-diseases, other severe immunological diseases (e.g. inborn errors of immunity )
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site
Department of Paediatrics, Herlev Hospital
Herlev, Capital Region, 2730
About this study
Official title: A Systems Biology Approach to Treatment of Food Allergy: A Randomized Controlled Trial of Oral Immunotherapy in Children Under 2 Years (SAFARI)
The goal of this clinical trial is to learn whether oral immunotherapy (OIT) is safe and effective for treating food allergy in children aged 0-2 years with peanut, tree nut, or sesame allergy. The study also aims to identify biological mechanisms and biomarkers associated with natural tolerance development and successful OIT using a systems biology approach.
The main questions it aims to answer are:
Read more
- Does oral immunotherapy increase the likelihood of successful desensitization and sustained unresponsiveness compared with allergen avoidance?
- Can immune, microbiome, metabolomic, genetic, and epigenetic profiles predict treatment response, natural tolerance development, and long-term outcomes?
Researchers will compare children receiving oral immunotherapy with children receiving standard care (allergen avoidance) to determine differences in treatment success, sustained unresponsiveness, safety, quality of life, and biological markers.
Participants will:
- Be randomized to either oral immunotherapy or allergen avoidance for 18-24 months.
- Undergo oral food challenges at study visits to assess allergic reactivity and treatment outcomes.
- Provide blood, urine, hair, skin swabs, skin tape strips, throat swabs, nasal lining fluid, and stool samples at baseline and at the end of the study for immune, microbiome, metabolomic, gene expression, and epigenetic analyses.
- Complete allergy assessments, including skin prick testing and clinical evaluations.
- Have allergic symptoms, adverse reactions, and development of other allergic diseases monitored throughout the study.
- Have parents complete questionnaires assessing food allergy-related quality of life, anxiety, and coping.
Read the detailed description
Food allergy affects approximately 4% of children worldwide and has increased over the past two decades, imposing substantial psychosocial and economic burden on affected families. For years, management relied on strict avoidance of the allergen and carrying an epinephrine autoinjector, which leads to tolerance development among 10-30% with peanut, tree-nut and sesame allergy. Treatments for food allergy such as biologics and oral immunotherapy (OIT) have shown a promising safety and efficacy profile in most studies, especially in younger children, but are not yet standard of care.
Biologics, including monoclonal antibodies targeting IgE (such as omalizumab) or key type 2 inflammatory pathways (e.g. dupilumab), offer an emerging strategy for managing food allergy. Used as stand-alone therapy, biologics can raise the threshold for allergic reactions and reduce symptom severity. Moreover, biologics have also been studied as adjuncts to OIT, where they may improve safety profiles, reduce dosing-related reactions, and facilitate more rapid desensitization. However, trials in young children assessing both safety, efficacy, mechanism and potential biomarkers are needed to inform personalized strategies, determining which children might benefit most from an avoidance strategy, OIT alone, biologics alone, or a combined approach. Currently, Palforzia is the only European Medicines Agency (EMA) approved OIT product available and approved for children from 4-17 years of age, whereas there are no OIT treatment options for the youngest children, where the prevalence of food allergy is highest.
Peanut OIT is gaining support based on real-world evidence, but OIT RCTs in young children under age 6 years are scarce and limited to studies of peanut and egg. The short term desensitization rates following peanut OIT range from 60% to 85%, and are higher when treatment begins in preschool age. Gastrointestinal and respiratory symptoms are common during peanut OIT, whereas rates of anaphylaxis requiring epinephrine are varying but relatively low, where up to 14% has been reported. Data for tree-nut OIT, e.g., hazelnut, cashew, pistachio, walnut and almond, is limited to a single-center retrospective study on hazelnut OIT in children < 18 years, and a single-center prospective cohort study on walnut OIT in children from 4-20 years. Further, data on tree-nut allergy has been extrapolated from an omalizumab-supported multifood OIT study in children from 4-15 years, which included cashew, walnut, hazelnut, and almond. Although outcomes and study design varied considerably, short term desensitization following tree-nut OIT ranged from 34% to 100%. Analysis of preliminary safety data is promising, with primarily mild reactions comparable with peanut OIT. Evidence for sesame OIT is very limited and solely based on small observational cohorts, case series, or extrapolated from multifood OIT protocols including sesame. Reported short term desensitization rates vary from 55% to 80%, and the majority of adverse reactions are mild.
Thus, while short term safety and efficacy of peanut, tree-nut, and sesame OIT seems promising, RCTs are needed in the youngest children, where food allergy is most prevalent. Moreover, although short term desensitization rates are encouraging, long term tolerance to the food - known as sustained unresponsiveness after discontinuing OIT - has proven more elusive. Follow-up studies show that many children relapse once therapy ends. Thus, there is a need for studies to identify underlying mechanisms and biomarkers predicting sustained unresponsiveness versus relapse, i.e. personalized treatment. In addition, some children will outgrow their food allergy during avoidance, i.e., natural tolerance development, but the mechanisms underlying natural tolerance are poorly understood, and no reliable predictors exist. Further, open-label quality-of-life (QoL) studies have consistently shown that OIT substantially reduces family anxiety concerning accidental exposures and improves daily functioning, but this still needs to be investigated in the youngest children in RCTs with a proper comparison of children undergoing avoidance vs. OIT. Finally, no previous study has investigated facilitators and barriers for implementing OIT in clinical practice, despite its higher resource demands and higher risk of adverse reactions compared to standard of care.
- Being tested
- Oral immunotheraphy (OIT)
- Keywords
- Food allergy, Oral immunotherapy, Children, Peanut Hypersensitivity, Sesame Hypersensitivity, Treenut Hypersensitivity, Immunotherapy, Peanut allergy, Sesame allergy, Tree nut allergy
- Medical subject headings
- Food Hypersensitivity, Peanut Hypersensitivity, Nut Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral immunotheraphy (OIT)Dietary supplement
Daily OIT will be administered with the relevant food allergen. Treatment includes gradual dose escalation over approximately 6 months, followed by a 12-month maintenance phase with daily intake of 300 mg food protein.
Assessment of sustained unresponsiveness:
Following completion of OIT and a successful end-of-treatment oral food challenge, participants in the OIT arm will undergo a second 1:1 randomization to either continued regular allergen consumption or allergen avoidance. After an additional 6 months, participants will undergo another oral food challenge to assess sustained unresponsiveness.
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm | Experimental | Participants will receive oral immunotherapy (OIT) for their diagnosed food allergy to peanut, tree nuts, or sesame. Receives: Dietary Supplement: Oral immunotheraphy (OIT) |
| Control arm | No intervention | Participants randomized to the control arm will follow standard of care consisting of avoidance of the relevant food allergen. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oral Food Challenge Response at End of Treatment
Effect of oral immunotherapy will be assessed by oral food challenge (OFC) at the end of treatment and compared with the control arm. Participants will be classified into predefined response categories: successful responders, defined as participants tolerating a 4000 mg food protein OFC; partial responders, defined as participants with an increased reaction threshold to at least 1000 mg food protein but not tolerating the final 4000 mg OFC and/or experiencing difficulties during up-dosing; and non-responders, defined as participants discontinuing OIT due to allergic reactions or having a reaction threshold below 1000 mg food protein.
Measured: End of treatment, approximately 18-24 months after randomization
Difficulty With Up-dosing During Oral Immunotherapy
Difficulty with up-dosing will be assessed in participants randomized to the OIT group. Difficulty is defined as allergic reactions, dose reductions, delayed dose escalation, temporary treatment interruption, or inability to complete the planned up-dosing phase according to protocol.
Measured: During the up-dosing phase, approximately 0-6 months after treatment initiation.
Sustained Unresponsiveness
Sustained unresponsiveness will be assessed by oral food challenge (OFC) after 6 months of either avoidance or regular intake of the allergenic food, according to randomization after completion of OIT. Success of the OFC will indicate potential long-term tolerance rather than transient desensitization.
Measured: 24-30 months after initial randomization, corresponding to approximately 6 months after completion of OIT.
Secondary outcomes (12)
Change in Gut Microbiome Diversity Assessed by Shannon Index
Change from baseline to end of treatment in gut microbiome diversity, assessed using the Shannon Index based on shotgun metagenomic sequencing of stool samples. Changes over time will be assessed within treatment groups and compared between treatment groups.
Measured: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in Fecal Metabolite Levels
Changes from baseline to end of treatment in fecal metabolite levels will be assessed using untargeted metabolomic profiling of stool samples. Changes in metabolite levels over time will be assessed within treatment groups, and differences in these changes will be compared between treatment groups.
Measured: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in Blood Immunoglobulin Markers
Changes from baseline to end of treatment in blood immunoglobulin markers, including food-specific IgG1 and IgG4 and total IgE, will be assessed. Changes over time will be assessed within treatment groups and compared between treatment groups.
Measured: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in Mast Cell Activation
Change from baseline to end of treatment in mast cell activation in response to peanut, sesame, and tree nuts will be assessed using the Mast Cell Activation Test (MAT). Changes over time will be assessed within treatment groups and compared between treatment groups.
Measured: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in Plasma Metabolite Levels
Changes from baseline to end of treatment in plasma metabolite levels will be assessed by metabolomic profiling using Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography-Mass Spectrometry (GC-MS) using the Global HD4 platform at Metabolon Inc., US. Changes in metabolite levels over time will be assessed within treatment groups, and differences in these changes will be compared between treatment groups.
Measured: Baseline to end of treatment, approximately 18-24 months after randomization.
Rate and Severity of Allergic Reactions During Oral Immunotherapy
The number and severity of anaphylaxis and other allergic reactions during OIT will be recorded at build-up visits and maintenance follow-up visits, including symptoms since the last visit, missed doses, accidental exposures, relevant cofactors, and treatments required. Reactions will be graded according to a modified World Allergy Organization grading system, grades 1 to 5, with adaptations specific to allergic reactions in infants.
Measured: From initiation of OIT to end of treatment, approximately 18-24 months after randomization.
Change in Parental Food Allergy-associated Anxiety and Coping
Changes in parental food allergy-associated anxiety, coping, and impact on daily life will be assessed using the Impairment Measure for Parental Food Allergy-Associated Anxiety and Coping Tool (IMPAACT). The questionnaire will be completed by parents at baseline and at the end of the randomized controlled trial, and changes will be assessed within and between treatment groups.
Measured: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in Allergic Sensitization
Changes in allergic sensitization to the relevant food allergen will be assessed by specific IgE and skin prick testing.
Measured: Baseline to end of treatment, approximately 18-24 months after randomization.
Development of New Allergic Sensitizations and Atopic Manifestations
The development of new food or inhalant sensitizations and new atopic manifestations will be assessed and compared between treatment groups. Atopic manifestations may include wheeze, allergic rhinitis, and atopic dermatitis. Atopic dermatitis will be assessed using established diagnostic criteria and severity scoring.
Measured: Baseline to end of treatment, approximately 18-24 months after randomization.
Prediction of Sustained Unresponsiveness
Different omics layers will be used to explore whether sustained unresponsiveness can be predicted.
Measured: Baseline to assessment of sustained unresponsiveness, approximately 24-30 months after randomization.
Change in PBMC Gene Expression Profiles
Changes from baseline to end of treatment in gene expression profiles will be assessed in peripheral blood mononuclear cells (PBMCs). Changes in gene expression over time will be assessed within treatment groups and compared between treatment groups and may additionally be evaluated as part of exploratory multivariate and multi-omics analyses.
Measured: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in PBMC Epigenetic Profiles
Changes from baseline to end of treatment in epigenetic profiles will be assessed in peripheral blood mononuclear cells (PBMCs). Changes in epigenetic markers over time will be assessed within treatment groups and compared between treatment groups and may additionally be evaluated as part of exploratory multivariate and multi-omics analyses.
Measured: Baseline to end of treatment, approximately 18-24 months after randomization.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2026
- Study startSep 2026 (estimated)
- Primary completion1 Mar 2031 (estimated)
- Study completionJun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (35)Papers the sponsor has linked to this study.
- Other trials for Food Allergy in ChildrenStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomized 1:1 to oral immunotherapy (OIT) or allergen avoidance. Following completion of OIT and successful end-of-treatment oral food challenge, participants in the OIT arm undergo a second randomization to either continued regular allergen consumption or allergen avoidance for assessment of sustained unresponsiveness.
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen Studies on Asthma in Childhood
- Sponsor type
- University, hospital or other
- Collaborators
- Herlev and Gentofte Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07825662
- Sponsor's protocol ID
- H-25096489
- Acronym
- SAFARI
- Status last verified
- Sep 2026
- First submitted
- 3 Sep 2026
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in publications (after de-identification), together with the study protocol, statistical analysis plan, and data dictionary, will be made available upon reasonable request to the corresponding author, subject to approval of a data access agreement and applicable ethical and legal requirements.
Publications
Huang J, Puglisi LH, Cook KA, Kelso JM, Wangberg H. Safety and Feasibility of Peanut, Tree Nut, and Sesame Oral Immunotherapy in Infants and Toddlers in a Real-World Setting. J Allergy Clin Immunol Pract. 2025 Jan;13(1):185-191.e3. doi: 10.1016/j.jaip.2024.09.025. Epub 2024 Sep 30.
PubMed 39357559Tang MLK, Lozinsky AC, Loke P. Peanut Oral Immunotherapy: State of the Art. Immunol Allergy Clin North Am. 2020 Feb;40(1):97-110. doi: 10.1016/j.iac.2019.09.005. Epub 2019 Nov 6.
PubMed 31761124Blackman AC, Staggers KA, Kronisch L, Davis CM, Anagnostou A. Quality of life improves significantly after real-world oral immunotherapy for children with peanut allergy. Ann Allergy Asthma Immunol. 2020 Aug;125(2):196-201.e1. doi: 10.1016/j.anai.2020.03.028. Epub 2020 Apr 8.
PubMed 32278075Epstein-Rigbi N, Goldberg MR, Levy MB, Nachshon L, Elizur A. Quality of Life of Food-Allergic Patients Before, During, and After Oral Immunotherapy. J Allergy Clin Immunol Pract. 2019 Feb;7(2):429-436.e2. doi: 10.1016/j.jaip.2018.06.016. Epub 2018 Jul 7.
PubMed 30129441Chinthrajah RS, Purington N, Andorf S, Long A, O'Laughlin KL, Lyu SC, Manohar M, Boyd SD, Tibshirani R, Maecker H, Plaut M, Mukai K, Tsai M, Desai M, Galli SJ, Nadeau KC. Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2019 Oct 19;394(10207):1437-1449. doi: 10.1016/S0140-6736(19)31793-3. Epub 2019 Sep 12.
PubMed 31522849Keet CA, Seopaul S, Knorr S, Narisety S, Skripak J, Wood RA. Long-term follow-up of oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2013 Sep;132(3):737-739.e6. doi: 10.1016/j.jaci.2013.05.006. Epub 2013 Jun 25. No abstract available.
PubMed 23806635Chua GT, Soller L, Kapur S, McHenry M, Rex GA, Cook VE, Cameron SB, Chan ES, Yeung J, Erdle SC. Real-world safety and effectiveness analysis of low-dose preschool sesame oral immunotherapy. J Allergy Clin Immunol Glob. 2023 Sep 23;3(1):100171. doi: 10.1016/j.jacig.2023.100171. eCollection 2024 Feb.
PubMed 37915725Wood RA, Kim JS, Lindblad R, Nadeau K, Henning AK, Dawson P, Plaut M, Sampson HA. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy. J Allergy Clin Immunol. 2016 Apr;137(4):1103-1110.e11. doi: 10.1016/j.jaci.2015.10.005. Epub 2015 Nov 12.
PubMed 26581915Shah A, Cox AL, Groetch M, Kattan JD, Schaible A, Sicherer SH, Tsuang A, Wang J, Oriel RC. Sesame oral immunotherapy outcomes in a pediatric cohort. J Allergy Clin Immunol Pract. 2025 Apr;13(4):938-940.e1. doi: 10.1016/j.jaip.2025.01.036. Epub 2025 Feb 8. No abstract available.
PubMed 39929303Nachshon L, Goldberg MR, Levy MB, Appel MY, Epstein-Rigbi N, Lidholm J, Holmqvist M, Katz Y, Elizur A. Efficacy and Safety of Sesame Oral Immunotherapy-A Real-World, Single-Center Study. J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2775-2781.e2. doi: 10.1016/j.jaip.2019.05.031. Epub 2019 May 29.
PubMed 31150789Andorf S, Purington N, Block WM, Long AJ, Tupa D, Brittain E, Rudman Spergel A, Desai M, Galli SJ, Nadeau KC, Chinthrajah RS. Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial. Lancet Gastroenterol Hepatol. 2018 Feb;3(2):85-94. doi: 10.1016/S2468-1253(17)30392-8. Epub 2017 Dec 12.
PubMed 29242014Elizur A, Appel MY, Nachshon L, Levy MB, Epstein-Rigbi N, Pontoppidan B, Lidholm J, Goldberg MR. Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study. Lancet Child Adolesc Health. 2019 May;3(5):312-321. doi: 10.1016/S2352-4642(19)30029-X. Epub 2019 Mar 27.
PubMed 30926371Moraly T, Pelletier de Chambure D, Verdun S, Preda C, Seynave M, Vilain AC, Chenivesse C, Delebarre-Sauvage C. Oral Immunotherapy for Hazelnut Allergy: A Single-Center Retrospective Study on 100 Patients. J Allergy Clin Immunol Pract. 2020 Feb;8(2):704-709.e4. doi: 10.1016/j.jaip.2019.10.045. Epub 2019 Nov 18.
PubMed 31751759Soller L, Carr S, Kapur S, Rex GA, McHenry M, Cook VE, Leo S, Wong T, Vander Leek TK, Gerstner TV, Yeung J, Abrams EM, Mak R, Hildebrand KJ, Erdle SC, Cameron SB, Chan ES. Real-world peanut OIT in infants may be safer than non-infant preschool OIT and equally effective. J Allergy Clin Immunol Pract. 2022 Apr;10(4):1113-1116.e1. doi: 10.1016/j.jaip.2021.12.009. Epub 2021 Dec 23. No abstract available.
PubMed 34954121Burks AW, Jones SM, Wood RA, Fleischer DM, Sicherer SH, Lindblad RW, Stablein D, Henning AK, Vickery BP, Liu AH, Scurlock AM, Shreffler WG, Plaut M, Sampson HA; Consortium of Food Allergy Research (CoFAR). Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012 Jul 19;367(3):233-43. doi: 10.1056/NEJMoa1200435.
PubMed 22808958
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Systems Biology Approach to Treatment of Food Allergy: A Randomized Controlled Trial of Oral Immunotherapy in Children Under 2 Years (SAFARI)
- ClinicalTrials.gov ID
- NCT07825662
- Acronym / sponsor ID
- SAFARI / H-25096489
- Keywords
- Food allergy, Oral immunotherapy, Children, Peanut Hypersensitivity, Sesame Hypersensitivity, Treenut Hypersensitivity, Immunotherapy, Peanut allergy
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Copenhagen Studies on Asthma in ChildhoodUniversity, hospital or other
- Collaborators
- Herlev and Gentofte Hospital
- Study start
- Sep 2026 (estimated)
- Primary completion
- 1 Mar 2031 (estimated)
- Study completion
- Jun 2031 (estimated)
- First posted
- 17 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn whether oral immunotherapy (OIT) is safe and effective for treating food allergy in children aged 0-2 years with peanut, tree nut, or sesame allergy. The study also aims to identify biological mechanisms and biomarkers associated with natural tolerance development and successful OIT using a systems biology approach.
The main questions it aims to answer are:
- Does oral immunotherapy increase the likelihood of successful desensitization and sustained unresponsiveness compared with allergen avoidance?
- Can immune, microbiome, metabolomic, genetic, and epigenetic profiles predict treatment response, natural tolerance development, and long-term outcomes?
Researchers will compare children receiving oral immunotherapy with children receiving standard care (allergen avoidance) to determine differences in treatment success, sustained unresponsiveness, safety, quality of life, and biological markers.
Participants will:
- Be randomized to either oral immunotherapy or allergen avoidance for 18-24 months.
- Undergo oral food challenges at study visits to assess allergic reactivity and treatment outcomes.
- Provide blood, urine, hair, skin swabs, skin tape strips, throat swabs, nasal lining fluid, and stool samples at baseline and at the end of the study for immune, microbiome, metabolomic, gene expression, and epigenetic analyses.
- Complete allergy assessments, including skin prick testing and clinical evaluations.
- Have allergic symptoms, adverse reactions, and development of other allergic diseases monitored throughout the study.
- Have parents complete questionnaires assessing food allergy-related quality of life, anxiety, and coping.
Detailed description
Food allergy affects approximately 4% of children worldwide and has increased over the past two decades, imposing substantial psychosocial and economic burden on affected families. For years, management relied on strict avoidance of the allergen and carrying an epinephrine autoinjector, which leads to tolerance development among 10-30% with peanut, tree-nut and sesame allergy. Treatments for food allergy such as biologics and oral immunotherapy (OIT) have shown a promising safety and efficacy profile in most studies, especially in younger children, but are not yet standard of care.
Biologics, including monoclonal antibodies targeting IgE (such as omalizumab) or key type 2 inflammatory pathways (e.g. dupilumab), offer an emerging strategy for managing food allergy. Used as stand-alone therapy, biologics can raise the threshold for allergic reactions and reduce symptom severity. Moreover, biologics have also been studied as adjuncts to OIT, where they may improve safety profiles, reduce dosing-related reactions, and facilitate more rapid desensitization. However, trials in young children assessing both safety, efficacy, mechanism and potential biomarkers are needed to inform personalized strategies, determining which children might benefit most from an avoidance strategy, OIT alone, biologics alone, or a combined approach. Currently, Palforzia is the only European Medicines Agency (EMA) approved OIT product available and approved for children from 4-17 years of age, whereas there are no OIT treatment options for the youngest children, where the prevalence of food allergy is highest.
Peanut OIT is gaining support based on real-world evidence, but OIT RCTs in young children under age 6 years are scarce and limited to studies of peanut and egg. The short term desensitization rates following peanut OIT range from 60% to 85%, and are higher when treatment begins in preschool age. Gastrointestinal and respiratory symptoms are common during peanut OIT, whereas rates of anaphylaxis requiring epinephrine are varying but relatively low, where up to 14% has been reported. Data for tree-nut OIT, e.g., hazelnut, cashew, pistachio, walnut and almond, is limited to a single-center retrospective study on hazelnut OIT in children < 18 years, and a single-center prospective cohort study on walnut OIT in children from 4-20 years. Further, data on tree-nut allergy has been extrapolated from an omalizumab-supported multifood OIT study in children from 4-15 years, which included cashew, walnut, hazelnut, and almond. Although outcomes and study design varied considerably, short term desensitization following tree-nut OIT ranged from 34% to 100%. Analysis of preliminary safety data is promising, with primarily mild reactions comparable with peanut OIT. Evidence for sesame OIT is very limited and solely based on small observational cohorts, case series, or extrapolated from multifood OIT protocols including sesame. Reported short term desensitization rates vary from 55% to 80%, and the majority of adverse reactions are mild.
Thus, while short term safety and efficacy of peanut, tree-nut, and sesame OIT seems promising, RCTs are needed in the youngest children, where food allergy is most prevalent. Moreover, although short term desensitization rates are encouraging, long term tolerance to the food - known as sustained unresponsiveness after discontinuing OIT - has proven more elusive. Follow-up studies show that many children relapse once therapy ends. Thus, there is a need for studies to identify underlying mechanisms and biomarkers predicting sustained unresponsiveness versus relapse, i.e. personalized treatment. In addition, some children will outgrow their food allergy during avoidance, i.e., natural tolerance development, but the mechanisms underlying natural tolerance are poorly understood, and no reliable predictors exist. Further, open-label quality-of-life (QoL) studies have consistently shown that OIT substantially reduces family anxiety concerning accidental exposures and improves daily functioning, but this still needs to be investigated in the youngest children in RCTs with a proper comparison of children undergoing avoidance vs. OIT. Finally, no previous study has investigated facilitators and barriers for implementing OIT in clinical practice, despite its higher resource demands and higher risk of adverse reactions compared to standard of care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants are randomized 1:1 to oral immunotherapy (OIT) or allergen avoidance. Following completion of OIT and successful end-of-treatment oral food challenge, participants in the OIT arm undergo a second randomization to either continued regular allergen consumption or allergen avoidance for assessment of sustained unresponsiveness.
| Arm | Type | Receives |
|---|---|---|
| Intervention arm | Experimental | Dietary Supplement: Oral immunotheraphy (OIT)Participants will receive oral immunotherapy (OIT) for their diagnosed food allergy to peanut, tree nuts, or sesame. |
| Control arm | No intervention | –Participants randomized to the control arm will follow standard of care consisting of avoidance of the relevant food allergen. |
Who may qualify
- Ages
- Up to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Children age 0-2 years
- Diagnosed IgE-mediated food allergy to tree-nuts, sesame, and/or peanuts, defined as: Positive oral food challenge (OFC) at inclusion or within 6 months before AND positive SPT (≥ 3 mm) or specific IgE (≥ 0.35 kUA/L)
- Both parents provide informed consent
Key exclusion criteria (3 listed)
- Already undergoing any form of immunotherapy
- Already undergoing any form of biological treatment
- Medical conditions precluding OITs: Uncontrolled asthma, atopic dermatitis requiring systemic therapy, eosinophilic esophagitis (EoE) and other GI-diseases, other severe immunological diseases (e.g. inborn errors of immunity )
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral immunotheraphy (OIT)Daily OIT will be administered with the relevant food allergen. Treatment includes gradual dose escalation over approximately 6 months, followed by a 12-month maintenance phase with daily intake of 300 mg food protein. Assessment of sustained unresponsiveness: Following completion of OIT and a successful end-of-treatment oral food challenge, participants in the OIT arm will undergo a second 1:1 randomization to either continued regular allergen consumption or allergen avoidance. After an additional 6 months, participants will undergo another oral food challenge to assess sustained unresponsiveness. | Dietary supplement | Intervention arm |
Primary outcome
Oral Food Challenge Response at End of Treatment
Time frame: End of treatment, approximately 18-24 months after randomization
Effect of oral immunotherapy will be assessed by oral food challenge (OFC) at the end of treatment and compared with the control arm. Participants will be classified into predefined response categories: successful responders, defined as participants tolerating a 4000 mg food protein OFC; partial responders, defined as participants with an increased reaction threshold to at least 1000 mg food protein but not tolerating the final 4000 mg OFC and/or experiencing difficulties during up-dosing; and non-responders, defined as participants discontinuing OIT due to allergic reactions or having a reaction threshold below 1000 mg food protein.
Difficulty With Up-dosing During Oral Immunotherapy
Time frame: During the up-dosing phase, approximately 0-6 months after treatment initiation.
Difficulty with up-dosing will be assessed in participants randomized to the OIT group. Difficulty is defined as allergic reactions, dose reductions, delayed dose escalation, temporary treatment interruption, or inability to complete the planned up-dosing phase according to protocol.
Sustained Unresponsiveness
Time frame: 24-30 months after initial randomization, corresponding to approximately 6 months after completion of OIT.
Sustained unresponsiveness will be assessed by oral food challenge (OFC) after 6 months of either avoidance or regular intake of the allergenic food, according to randomization after completion of OIT. Success of the OFC will indicate potential long-term tolerance rather than transient desensitization.
12 secondary outcomes
Change in Gut Microbiome Diversity Assessed by Shannon Index
Time frame: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in Fecal Metabolite Levels
Time frame: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in Blood Immunoglobulin Markers
Time frame: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in Mast Cell Activation
Time frame: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in Plasma Metabolite Levels
Time frame: Baseline to end of treatment, approximately 18-24 months after randomization.
Rate and Severity of Allergic Reactions During Oral Immunotherapy
Time frame: From initiation of OIT to end of treatment, approximately 18-24 months after randomization.
Change in Parental Food Allergy-associated Anxiety and Coping
Time frame: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in Allergic Sensitization
Time frame: Baseline to end of treatment, approximately 18-24 months after randomization.
Development of New Allergic Sensitizations and Atopic Manifestations
Time frame: Baseline to end of treatment, approximately 18-24 months after randomization.
Prediction of Sustained Unresponsiveness
Time frame: Baseline to assessment of sustained unresponsiveness, approximately 24-30 months after randomization.
Change in PBMC Gene Expression Profiles
Time frame: Baseline to end of treatment, approximately 18-24 months after randomization.
Change in PBMC Epigenetic Profiles
Time frame: Baseline to end of treatment, approximately 18-24 months after randomization.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Background: PubMed 39357559Huang J, Puglisi LH, Cook KA, Kelso JM, Wangberg H. Safety and Feasibility of Peanut, Tree Nut, and Sesame Oral Immunotherapy in Infants and Toddlers in a Real-World Setting. J Allergy Clin Immunol Pract. 2025 Jan;13(1):185-191.e3. doi: 10.1016/j.jaip.2024.09.025. Epub 2024 Sep 30.
- Background: PubMed 31761124Tang MLK, Lozinsky AC, Loke P. Peanut Oral Immunotherapy: State of the Art. Immunol Allergy Clin North Am. 2020 Feb;40(1):97-110. doi: 10.1016/j.iac.2019.09.005. Epub 2019 Nov 6.
- Background: PubMed 32278075Blackman AC, Staggers KA, Kronisch L, Davis CM, Anagnostou A. Quality of life improves significantly after real-world oral immunotherapy for children with peanut allergy. Ann Allergy Asthma Immunol. 2020 Aug;125(2):196-201.e1. doi: 10.1016/j.anai.2020.03.028. Epub 2020 Apr 8.
- Background: PubMed 30129441Epstein-Rigbi N, Goldberg MR, Levy MB, Nachshon L, Elizur A. Quality of Life of Food-Allergic Patients Before, During, and After Oral Immunotherapy. J Allergy Clin Immunol Pract. 2019 Feb;7(2):429-436.e2. doi: 10.1016/j.jaip.2018.06.016. Epub 2018 Jul 7.
- Background: PubMed 31522849Chinthrajah RS, Purington N, Andorf S, Long A, O'Laughlin KL, Lyu SC, Manohar M, Boyd SD, Tibshirani R, Maecker H, Plaut M, Mukai K, Tsai M, Desai M, Galli SJ, Nadeau KC. Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2019 Oct 19;394(10207):1437-1449. doi: 10.1016/S0140-6736(19)31793-3. Epub 2019 Sep 12.
- Background: PubMed 23806635Keet CA, Seopaul S, Knorr S, Narisety S, Skripak J, Wood RA. Long-term follow-up of oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2013 Sep;132(3):737-739.e6. doi: 10.1016/j.jaci.2013.05.006. Epub 2013 Jun 25. No abstract available.
- Background: PubMed 37915725Chua GT, Soller L, Kapur S, McHenry M, Rex GA, Cook VE, Cameron SB, Chan ES, Yeung J, Erdle SC. Real-world safety and effectiveness analysis of low-dose preschool sesame oral immunotherapy. J Allergy Clin Immunol Glob. 2023 Sep 23;3(1):100171. doi: 10.1016/j.jacig.2023.100171. eCollection 2024 Feb.
- Background: PubMed 26581915Wood RA, Kim JS, Lindblad R, Nadeau K, Henning AK, Dawson P, Plaut M, Sampson HA. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy. J Allergy Clin Immunol. 2016 Apr;137(4):1103-1110.e11. doi: 10.1016/j.jaci.2015.10.005. Epub 2015 Nov 12.
- Background: PubMed 39929303Shah A, Cox AL, Groetch M, Kattan JD, Schaible A, Sicherer SH, Tsuang A, Wang J, Oriel RC. Sesame oral immunotherapy outcomes in a pediatric cohort. J Allergy Clin Immunol Pract. 2025 Apr;13(4):938-940.e1. doi: 10.1016/j.jaip.2025.01.036. Epub 2025 Feb 8. No abstract available.
- Background: PubMed 31150789Nachshon L, Goldberg MR, Levy MB, Appel MY, Epstein-Rigbi N, Lidholm J, Holmqvist M, Katz Y, Elizur A. Efficacy and Safety of Sesame Oral Immunotherapy-A Real-World, Single-Center Study. J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2775-2781.e2. doi: 10.1016/j.jaip.2019.05.031. Epub 2019 May 29.
- Background: PubMed 29242014Andorf S, Purington N, Block WM, Long AJ, Tupa D, Brittain E, Rudman Spergel A, Desai M, Galli SJ, Nadeau KC, Chinthrajah RS. Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial. Lancet Gastroenterol Hepatol. 2018 Feb;3(2):85-94. doi: 10.1016/S2468-1253(17)30392-8. Epub 2017 Dec 12.
- Background: PubMed 30926371Elizur A, Appel MY, Nachshon L, Levy MB, Epstein-Rigbi N, Pontoppidan B, Lidholm J, Goldberg MR. Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study. Lancet Child Adolesc Health. 2019 May;3(5):312-321. doi: 10.1016/S2352-4642(19)30029-X. Epub 2019 Mar 27.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in publications (after de-identification), together with the study protocol, statistical analysis plan, and data dictionary, will be made available upon reasonable request to the corresponding author, subject to approval of a data access agreement and applicable ethical and legal requirements.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oral immunotheraphy (OIT) in people with Food Allergy in Children and Oral Immunotherapy for Food Allergy, run by Copenhagen Studies on Asthma in Childhood at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bo Chawes (+4538681152, chawes@copsac.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oral Food Challenge Response at End of Treatment (time frame: End of treatment, approximately 18-24 months after randomization). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07825662, which also lists 35 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.