Evaluation of the Efficacy of Oral Immunotherapy With Raw Apple in Patients Allergic to Birch Pollen and Apple: Prospective, Multicenter, Comparative Phase III Study (ELIO)

Apple-birch pollen-food allergy syndrome is particularly common in Northern and Central Europe (70% of patients allergic to birch pollen), and classically induces an oral syndrome that impairs patients' quality of life. Current treatment is based on food avoidance. However, evidence of the efficacy of this treatment is limited (small numbers, lack of validation with a control group, absence of double-blind evaluation of the primary endpoint in a challenge test against placebo). The aim of oral immunotherapy with raw apple is to improve the management of allergic patients by enabling them to acquire tolerance to raw apple and other rosacea.

Study Overview

• Status: Recruiting
• Conditions: Allergies
• Intervention / Treatment: Other: oral provocation test

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anays PIOTIN, Dr; Phone Number: +33 03.69.55.00.49; Email: anays.piotin@chru-strasbourg.fr

Study Locations

• France
  • Besançon, France, 25030
    • Not yet recruiting
    • Chu Jean Minjoz
    • Contact: Fabien PELLETIER, Doctor; Phone Number: +33 +33 381416060; Email: fpelletier@chu-besancon.fr
  • Dijon, France, 21079
    • Recruiting
    • Hopital François Mitterrand Chu Dijon
    • Contact: Philippe BONNIAUS, Professor; Phone Number: +33 +33 380293772; Email: philippe.bonniaud@chu-dijon.fr
  • Reims, France, 51092
    • Not yet recruiting
    • Hopital Maison Blanche Chu Reims
    • Contact: Jeanne-Marie PEROTIN-COLLARD, Professor; Phone Number: +33 +33 326787609; Email: jmperotin-collard@chu-reims.fr
  • France
    • Strasbourg, France, France, 67000
      • Recruiting
      • Hôpitaux Universitaires de Strasbourg
      • Contact: Anays Dr PIOTIN; Phone Number: +33 03.69.55.00.49; Email: anays.piotin@chru-strasbourg.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient with allergic rhinitis to birch pollen.
• Patient with an oral syndrome within 15 minutes of consuming at least one of the first 3 doses of raw apple in the V0 or V1 raw apple oral challenge test.
• Evidence of sensitization to PR10 proteins in birch pollen and apple: positive prick tests to birch pollen and raw Golden apple and/or positive Bet v 1 and Mal d 1 specific IgE assays.
• Subject affiliated to a social health insurance scheme
• Subject able to understand the aims and risks of the research and to give dated and signed informed consent
• For women of childbearing age: negative urine pregnancy test at inclusion visit

Exclusion Criteria:

• Severe or uncontrolled asthma
• Severe obstructive syndrome
• Active neoplastic disease
• Active autoimmune disease
• Eosinophilic esophagitis or other active eosinophilic gastrointestinal pathologies
• History of bariatric surgery
• History of anaphylaxis to apples
• Allergy to cooked apples
• Contraindication to anti-histamines, corticoids, salbutamol, adrenaline
• Other contraindication to an oral challenge test
• Allergy to placebo ingredients
• Presence of oral syndrome during consumption of placebo in the first oral challenge test
• Allergenic immunotherapy to birch pollen in progress or completed less than 5 years ago
• Current treatment with anti-IgE, anti-IL4/13, anti-IL5 or anti-TSLP biotherapy.
• Impossibility of giving the subject informed information
• Subject under court protection
• Subject under guardianship or curatorship
• Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral immunotherapy; oral immunotherapy with raw apple during 9 month	Other: oral provocation test; Progressively increasing doses of peeled fresh Golden apple or placebo will be consumed by the patient (4g, 12g, 40g, 120g) with a time interval of 20 minutes between each dose.
Placebo Comparator: eviction; avoidance of raw apples for 9 months	Other: oral provocation test; Progressively increasing doses of peeled fresh Golden apple or placebo will be consumed by the patient (4g, 12g, 40g, 120g) with a time interval of 20 minutes between each dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of oral immunotherapy to raw apple on the reduction of oral raw apple syndrome	To evaluate the efficacy of oral immunotherapy to raw apple on the reduction of oral raw apple syndrome after 9 months of oral immunotherapy. A reduction in oral syndrome after 9 months of oral immunotherapy with raw apple is defined as: absence of oral syndrome on the 9-month raw apple OPT when consuming a dose of raw apple 3 times greater than the dose of raw apple triggering oral syndrome on the initial raw apple oral challenge.	9 month

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2025
• Primary Completion (Estimated): May 5, 2027
• Study Completion (Estimated): May 5, 2027

Study Registration Dates

• First Submitted: January 7, 2025
• First Submitted That Met QC Criteria: January 7, 2025
• First Posted (Actual): January 13, 2025

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: allergy; oral immunotherapy
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity
• Other Study ID Numbers: 9432

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No