Phase II-III study to assess the efficacy and safety of sublingual immunotherapy in patients suffering from birch pollen allergy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ROXALL Medizin GmbH

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2025-05-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Roxall Medizin GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Dose response

The purpose of this trial is to establish the most effective and best-tolerated dose of SLI-RX-BET in terms of benefit-risk balance and CSMS (Combined Symptom and Medication Score).

Conditions and MedDRA coding

Patients with moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to birch pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline (Bousquet et al., 2008)

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

No

IPD plan description

No plan

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients who signed and dated the informed consent form obtained prior to any study-specific examination
2. Female or male patients between 18 and 65 years of age at the time of signing the informed consent form
3. Patients with moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to birch pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, either with well-controlled mild-to-moderate asthma defined in GINA guideline (Global Initiative for Asthma, 2024) or without asthma
4. Forced expiratory volume (FEV1) in one second > 70 % of predicted normal value (only for asthmatic patients)
5. Sensitization to Betula verrucosa pollen, verified by: positive skin prick test (wheal diameter ≥ 3 mm and negative control < 2 mm and positive (histamine) control ≥ 3 mm) and serum allergen-specific IgE to Betula verrucosa ≥ 0.7 kU/L (CAP EAST class ≥ 2) and a Retrospective Rhinoconjunctivitis Total Symptom Score (RRTSS) ≥ 2 (0-3 scale) based on the most severe days during one of the two BPS preceding enrolment and positive response to nasal provocation with Betula verrucosa pollen allergen extract (at least at the third concentration step)
6. Assumed compliance and ability of the patient to understand the patient’s electronic diary and to follow the instructions of the study staff
7. Compliance and ability of the patient to complete an electronic diary for self-evaluation of the symptoms and rescue medication
8. Safety laboratory results within the normal range or considered to be not clinically significant in any other case

Exclusion criteria 32

1. Previous immunotherapy with birch pollen allergen extracts according to the homologous group of tree pollen of the "Birch group" / “Fagales group”, as defined in Annex 1 in the Guideline on allergen products: production and quality issues (EMEA/CHMP/BWP/304831/2008), within the last 5 years
2. Patients with co-sensitizations or co-allergies to any perennial or seasonal allergen (with exception of alder, hazel and hornbeam), which interfere with the conduct of the study (e. g. with the tNPT or the CSMS recording), especially if the result in SPT for this allergen is higher than that for Betula verrucosa
3. Patients with co-sensitizations to any perennial or seasonal allergen overlapping during PBPP or BPS but which are not cross-reactive with Betula verrucosa and, measured at the same time, with specific IgE levels ≥ class 2 CAP/PHADIA (unless the relevance can be excluded by component resolved diagnosis)
4. Simultaneous participation in other clinical trials
5. Simultaneous specific immunotherapy with other allergens
6. Participation, meaning randomization, in a trial in the last three months before enrolment
7. Contraindications for SLIT (Pitsios et al., 2015)
8. Contraindications for SPT
9. Contraindications for NPT
10. Serious systemic reactions to allergen-specific immunotherapy in the past
11. Hypersensitivity to excipients of the IMP
12. Any severe or unstable lung disease e. g. active tuberculosis, cystic fibrosis, COPD
13. Severe, or partly controlled or uncontrolled asthma according to GINA guideline (Global Initiative for Asthma, 2024)
14. Asthmatic patients with FEV1 ≤ 70 % of predicted normal value at screening
15. Chronic or severe acute diseases of nose or eyes
16. Irreversible secondary disorders of the target organs (e. g. emphysema, bronchiectasis)
17. Therapy with immunoglobulins
18. Completed or ongoing treatment with an anti-IgE-antibody (like omalizumab) and/or checkpoint-inhibitor
19. Diseases of the immune system including autoimmune and immune deficiencies (with exception to well-controlled Hashimoto thyroiditis and type-1 diabetes mellitus)
20. Severe acute or chronic inflammatory or infectious diseases
21. Chronic or acute diseases of the heart, kidney or liver with severe impairment of their function
22. Malignancy within the previous 5 years
23. Active chronic urticaria
24. Active severe atopic eczema
25. Alcohol, drug, or medication abuse within the past year and/or during the study
26. Existing or intended pregnancy, lactation or inadequate contraceptive measures for woman with childbearing potential or a positive pregnancy test at screening
27. Use of non-allowed medication
28. Severe psychiatric, psychological, or neurological disorders; completed or ongoing long-term treatment with tranquilizer or psychoactive drugs (including tricyclic anti-depressants)
29. Relationship or dependence with the sponsor and/or investigator
30. Legal incapacity
31. Patients who are jurisdictional or governmentally institutionalized
32. Risk of non-compliance by the patient with the study procedures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary (efficacy) endpoint is defined as the absolute differences in mean CSMS (Combined Symptom and Medication Score) during Peak Birch Pollen Period (PBPP) of each active treatment group compared with placebo treatment group.

Secondary endpoints 10

1. Absolute and relative differences in mean CSMS during the Birch Pollen Season (BPS) between active and placebo treatment groups.
2. Absolute and relative differences in mean dSS during PBPP and BPS.
3. bsolute and relative differences in the 6 mean individual symptom scores (4 nasal and 2 ocular) during PBPP and BPS.
4. Absolute and relative differences in mean dMS during PBPP and BPS.
5. Global Rhinoconjunctivitis Discomfort with a 10.0-point Visual Analogue Scale (VAS).
6. Change in Rhinoconjunctivitis quality of life questionnaire (RQLQ) between active and placebo treatment groups comparing basal and post-treatment scoring.
7. Well and severe days: A well day is defined as a day without administration of any rescue medication (dMS = 0) and with dSS < 0.34 (range 0-3). A severe day is defined (acc. to Pfaar et al., 2014) as a day with a single score = 3 in any of the six symptoms. Percentages of well and severe days will be calculated for each subject as the number of well or severe days in the PBPP and BPS in relation to the number of days comprising both periods.
8. Symptom-free days during PBPP and PBP are defined as the days with absence of symptoms, (dSS = 0), and without administration of any rescue medication (dMS = 0), expressed as percentage of days during the PBPP and BPS.
9. tNPT titrated Nasal Provocation Test: To assess the efficacy of each dose of SLI-RX-BET compared to placebo. Defined as percentage of patients with an increased dosing step and the change in number of dosing steps needed to provoke a positive response in the titrated nasal provocation test (tNPT) post-treatment compared with pre-treatment (i. e. any improvement) in each of the four study groups.This is based on the change of the response to nasal provocation (tNPT)
10. To analyse the safety and tolerability of each dose of SLI-RX-BET compared to placebo by Treatment-Emergent Adverse Drug Reactions (TEADR) and patients affected with TEADRs in each group.

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ROXALL Medizin GmbH

Sponsor organisation

ROXALL Medizin GmbH

Address

Carl-Petersen-Strasse 4, Hamm-Nord Hamm-Nord

City

Hamburg

Postcode

20535

Country

Germany

Scientific contact point

Organisation

ROXALL Medizin GmbH

Contact name

Leire Begona

Public contact point

Organisation

ROXALL Medizin GmbH

Contact name

Dr. Elshan Aghayev

Third parties 2

Locations

1 EU/EEA country · 3 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 19 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