Sublingual Birch Immunotherapy for Pollen-associated Food Allergy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-05-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate superiority of a short-course SLIT with ITULAZAX over placebo in reducing pollen-associated food allergy symptoms during standardized apple challenge.

Secondary objectives 8

1. To assess whether oral gargling with Infectodiarrstop LGG Mono (Lactobacilli) modifies the clinical efficacy of SLIT or placebo (i.e. comparing SLIT + Lactobacilli with SLIT and placebo + Lactobacilli with placebo).
2. To assess the efficacy of a short-course SLIT with ITULAZAX compared with placebo with regards to other symptoms during standardized apple challenge
3. To assess whether oral gargling with Infectodiarrstop LGG Mono (Lactobacilli) modifies the clinical efficacy of SLIT or placebo (i.e. comparing SLIT + Lactobacilli with SLIT and placebo + Lactobacilli with placebo) with regards to other symptoms during standardized apple challenge.
4. To assess the efficacy of a short-course SLIT with ITULAZAX compared with placebo with regards to other symptom variables
5. To assess whether oral gargling with Infectodiarrstop LGG Mono (Lactobacilli) modifies the clinical efficacy of SLIT or Placebo (i.e. comparing SLIT + Lactobacilli with SLIT and placebo + Lactobacilli with placebo) with regards to other variables.
6. To assess the efficacy of a short-course SLIT with ITULAZAX compared with placebo with regards to changes in paramount biomarkers IgE and IgG4 in serum with ITULAZAX® or Placebo
7. To assess whether oral gargling with INFECTODIARRSTOP® LGG® Mono Infectodiarrstop LGG Mono (Lactobacilli) modifies the clinical efficacy of SLIT or Placebo (i.e. comparing SLIT + Lactobacilli with SLIT and placebo + Lactobacilli with placebo) with regards to changes in paramount biomarkers IgE and IgG4 in serum
8. To assess RDF in patients with additional irritable bowel syndrome (IBS subgroup)

Conditions and MedDRA coding

Pollen-associated Food Allergy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Written informed consent available.
2. Male and female patients aged between 18 to 65 years.
3. Female participants with reproductive potential must have a negative beta-HCG serum pregnancy test as part of the screening visit.
4. Female participants with reproductive potential must have in addition a negative urine pregnancy test on the day of randomization.
5. Female participants with reproductive potential are required to use an acceptable birth control method. Acceptable birth control methods that result in a failure rate of less than 1% include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence. Acceptable birth control methods that result in a failure rate of more than 1% per year include: progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action, male of female condom with or without spermicide, cap, diaphragm or sponge with spermicide
6. Sensitization to Birch pollen as evidenced by a wheal >5mm in skin prick test and specific IgE against Betv1 > CAP class 2.
7. Minimum compound global VAS of 3 for itch, stinging and prickling within 5 minutes after controlled apple challenge prior to randomization.
8. The patient is able to understand the clinical trial and cooperate with the investigator.
9. Patient history of moderate to severe allergic rhinitis and/or conjunctivitis (AR/C) with or without asthma to birch since more than 2 years
10. Patient history of birch pollen related food syndrome since more than 2 years with relevant symptoms to apple and a relevant FAQLQ/FAIM score ≥ 2.
11. Sensitization to apple as evidenced by specific IgE against Mald1 > CAP class 1.

Exclusion criteria 20

1. Pregnancy or wish to become pregnant or lactation.
2. Uncontrolled asthma or FEV1 <80%.
3. Severe atopic dermatitis.
4. Currently relevant history of eosinophil esophagitis.
5. Patients with acute severe oral inflammation or oral wounds.
6. Allergen-Immunotherapy within past 5 years.
7. History of any other currently relevant the immune-system affecting pathology apart from allergy, such as e.g. active autoimmune diseases, malignancies, infectious diseases.
8. History of currently relevant severe medical condition such as diabetes, severe hypertension, kidney, liver, gut or heart disease that requires treatment.
9. History of currently relevant addiction (e.g. such as alcohol or drugs).
10. History of currently relevant psychiatric disorder.
11. Current or relevant history of intake of Betablockers, ACE-inhibitors, systemic steroids or immune-suppressants, antidepressants, neuroleptics or biologics.
12. History of anaphylaxis to Birch-related food allergens or history of more than 2 systemic allergic reactions.
13. Current participation in another clinical trial or participation in another clinical trial with IMP intake and if applicable wash-out phase within the last four weeks.
14. Any history of laryngeal edema to birch-related food allergens.
15. Any other history of currently relevant urticaria or angioedema.
16. Maximum compound global VAS of ≥9 for itch, stinging and prickling after controlled apple challenge prior to randomization.
17. Clinically relevant sensitization to nsLTP and other food relevant heat- stabile allergens as evidenced by spec. IgE > CAP class 1 and symptoms to cooked/processed fruit allergen sources.
18. Intolerance to drug ingredients, these includes besides the active pharmaceutical ingredients: D-Glucose, Saccharose, Aspartame, Maltodextrin, Sodium ascorbate, Gelatine (fish source), Mannitol, Sodium hydroxide.
19. Intolerance to the ingredients and contraindications of the rescue medication: Ceterizin: Sensitivity against Ceterizin and other ingredients, Hydroxyzine and other Piperazine derivatives. Patients with end-stage renal disease and an eGFR (estimated glomerular filtration rate) below 15 ml/min. Prednisolon: Sensitivity against Prednisolone and other ingredients
20. Elevated serum-tryptase or any history of mastocytosis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to Visit 5 in the combined global VAS (itching, stinging, prickling within 5 minutes after apple challenge)

Secondary endpoints 16

1. Change from baseline to Visit 5 in the combined global VAS (itching, stinging, prickling within 5 minutes after apple challenge)
2. Change from baseline to Visit 5 in the Modified Bergmann Score
3. Change from baseline to Visit 5 in FAQLQ/FAIM total score
4. Change from baseline to Visit 5 in asthma symptoms and disease control total score (in asthmatic patients)
5. Change from baseline to Visit 5 in RDF symptoms (in IBS subgroup)
6. Incidence of solicited treatment-emergent local and systemic reactions (WAO grading)
7. Incidence of unsolicited treatment-emergent AEs and SAEs
8. Incidence of anaphylaxis events
9. Physical examinations and vital signs
10. Use of rescue medication (Ceterizine, Prednisolon) to relief allergic symptoms as side effects
11. Use of emergency medication (systemic steroids, high-dose antihistamines or adrenaline) to treat side-effects of the apple challenge
12. Safety laboratory data
13. Likert Tolerability Scale Score for treatment
14. Change from baseline to Visit 5 in 5-point Likert Tolerability Scale Score after apple challange
15. Treatment adherence (days of IMP intake vs. non-intake, drug accountability).
16. Change from baseline to Visit 5 in systemic (serum concentrations of) total IgE, specific IgE, and IgG4 for Mal d1 and Bet v1

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)

Sponsor organisation

Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)

Address

Ismaninger Strasse 22, Au-Haidhausen Au-Haidhausen

City

Munich

Postcode

81675

Country

Germany

Scientific contact point

Organisation

Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)

Contact name

Zentrum für Allergie und Umwelt, AG Allergologie

Public contact point

Organisation

Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)

Contact name

Zentrum für Allergie und Umwelt, AG Allergologie

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications