Phase II-III study to assess the efficacy and safety of sublingual immunotherapy in patients suffering from grass 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]

Trial duration

22 Oct 2025 → ongoing

Decision date (initial)

2025-09-05

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: Efficacy, Dose response, Safety, Therapy

The purpose of this trial is to establish the efficacy and safety of SLI-RX-PHL in terms of CSMS (Combined Symptom and Medication Score) and benefit-risk balance between the different doses.

Conditions and MedDRA coding

Patients with moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to grass 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 grass 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 Phleum pratense 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 Phleum pratense ≥ 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 GPS preceding enrolment and positive response to nasal provocation with Phleum pratense 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 31

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

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 Grass Pollen Period (PGPP) of each active treatment group compared with placebo treatment group.

Secondary endpoints 10

1. Absolute and relative differences in mean CSMS during Grass Pollen Season (GPS) between active and placebo treatment groups.
2. Absolute and relative differences in mean dSS during PGPP and GPS
3. Absolute and relative differences in the 6 mean individual symptom scores (4 nasal and 2 ocular) during PGPP and GPS
4. Absolute and relative differences in mean dMS during PGPP and GPS.
5. Change in Global Rhinoconjunctivitis Discomfort with a 10.0-point Visual Analogue Scale (VAS) between active and placebo treatment groups comparing pre- (baseline) and post-treatment scaling.
6. Change in Rhinoconjunctivitis quality of life questionnaire (RQLQ) between active and placebo treatment groups comparing pre- (baseline) 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 PGPP and GPS in relation to the number of days comprising both periods.
8. Symptom-free days 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 PGPP and GPS.
9. titrated Nasal Provocation Test to assess the efficacy of each dose of SLI-RX-PHL compared to placebo. Defined as % of patients with an increased dosing step and change in number of dosing steps needed to provoke a positive response in the tNPT post-treatment compared with pre-treatment (i. e. any improvement) in each of the 4 treatment groups. This is based on the change of the response to nasal provocation (tNPT) from baseline (pre-treatment) to post-treatment.
10. To analyse the safety and tolerability of each dose of SLI-RX-PHL 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

Dr. Madariaga Begoña

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

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

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