Phase II-III study to assess the efficacy and safety of subcutaneous cluster-immunotherapy in patients suffering from house dust mite 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

7 May 2025 → 30 Mar 2026

Decision date (initial)

2025-03-12

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, Therapy, Efficacy, Dose response

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

Conditions and MedDRA coding

Moderate-to-severe allergic rhinitis / rhino-conjunctivitis due to house dust mites (HDM) for at least one year according to the "Allergic Rhinitis and its Impact on Asthma" (ARIA, Bousquet et al., 2008) guideline,

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 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 / rhino-conjunctivitis due to house dust mites (HDM) for at least one year according to the Allergic Rhinitis and its Impact on Asthma (ARIA, Bousquet et al., 2008) 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 > 80 % of predicted normal value (only for asthmatic patients)
5. Sensitization to Dermatophagoides pteronyssinus, 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 D. pteronyssinus ≥ 0.7 kU/L (CAP EAST class ≥ 2) and a Retrospective Rhinitis Total Symptom Score (RRTSS) ≥ 2 (0-3 scale) based on the most severe days during winter preceding enrolment and positive response to nasal provocation with D. pteronyssinus 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 34

1. Previous immunotherapy with allergen extract of house dust mites (HDM) according to the homologous group of the Dermatophagoides genus, 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 D. farinae), 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 D. pteronyssinus
3. Patients with co-sensitizations to any perennial or seasonal allergen with overlapping during PMP but which are not cross-reactive with D. pteronyssinus and with specific IgE levels ≥ class 2 CAP/PHADIA
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 SCIT (Pitsios et al., 2015; Pfaar et al., 2022)
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 ≤ 80 % 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 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 (any renal failure for patients in the subgroup for aluminum PK determinations)
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. Systemic and local (eye drops) treatment with beta-blockers
28. Use of non-allowed medication
29. Contraindication for adrenalin (for example, acute or chronic symptomatic coronary heart disease, severe hypertension, hyperthyroidism, glaucoma)
30. Severe psychiatric, psychological, or neurological disorders; completed or ongoing long-term treatment with tranquilizer or psychoactive drugs (including tricyclic anti-depressants)
31. Relationship or dependence with the sponsor and/or investigator
32. Legal incapacity
33. Patients who are jurisdictional or governmentally institutionalized
34. 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 PMP of each active treatment group compared to placebo treatment group.

Secondary endpoints 7

1. Absolute and relative differences in mean dSS during PMP.
2. Absolute and relative differences in mean dMS during PMP.
3. Global Rhinoconjunctivitis Discomfort with a 10-point Visual Analogue Scale (VAS).
4. Change in Rhinoconjunctivitis quality of life questionnaire (RQLQ) between active and placebo treatment groups comparing basal and post-treatment scoring.
5. Well and severe days: A well day is defined as a day without administration of any rescue medication (dMS = 0) and with dSS < 0.5 (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 four symptoms. Percentages of well and severe days will be calculated for each subject as the number of well or severe days in the PMP in relation to 56 days comprising the PMP.
6. 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 PMP.
7. tNPT: To assess the efficacy of each dose of CLU-RX-DPT compared to placebo. Defined as % of patients with an increased dosing step and the change in number of dosing steps needed to provoke a positive response in the tNPT post-treatment compared with pre-treatment in each of the 4 study groups. This is based on the change of the response to nasal provocation with incremental concentrations of an allergen extract of D. pteronyssinus from basline to end of treatment.

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 1

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

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

Documents 27 files

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

Application history

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