Study to evaluate the safety and efficacy of a treatment consisting of immunotherapy by subcutaneous injection of a combination of Der p 1/Der p 2/Der p 23 allergens at different doses in patients with allergic rhinitis or rhinoconjunctivitis with or without allergic asthma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Diater Laboratorio De Diagnostico Y Aplicaciones Terapeuticas S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

10 Apr 2025 → ongoing

Decision date (initial)

2025-03-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Therapy, Safety

To evaluate the benefit/risk balance of 3 of ITSC doses with the main allergens of D. pteronyssinus Der p 1/Der p 2/Der p 23 purified to find the optimal dose after having received 12 maintenance doses.

Secondary objectives 5

1. Describe the sociodemographic and clinical profile of the patient and its possible correlation with safety, efficacy or immunologic outcomes
2. Evaluate the efficacy of 3 doses of ITSC by the change from baseline to after receiving 6 and 12 maintenance doses of global and specific efficacy variables for the entire population analyzed. In the case of the asthmatic subpopulation, for the variables that apply.
3. To evaluate the percentage of patients who obtain improvement in the conjunctival provocation test (PPC) after 6 and 12 maintenance doses.
4. To evaluate the immune response against D. pteronyssinus and Der p 1/Der p 2/Der p 23 after administration of ITSC after 6 and 12 maintenance doses.
5. To evaluate the safety of 3 doses of ITSC with the major allergens of D. pteronyssinus, Der p 1/Der p 2/Der p 23 purified throughout the study.

Conditions and MedDRA coding

moderate/severe allergic rhinitis/rhinoconjunctivitis with/without controlled allergic asthma due to sensitization to Dermatophagoides genus

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients/legal representatives who have understood and signed the informed consent or assent form.
2. Patients between 12 and 65 years of age, both inclusive.
3. Patients with moderate or severe persistent allergic rhinitis and/or rhinoconjunctivitis (according to ARIA2 guidelines) for at least the last year, caused by clinically relevant sensitization to Dermatophagoides genus, fulfilling all the criteria described below: 3.a. Clinical history with symptoms compatible with demonstrated hypersensitivity to the genus Dermatophagoides. 3.b. Positive skin prick test (papule of ≥3 mm with respect to the negative control) against at least one of the following major allergens: Der p 1, Der p 2 or Der p 23 performed at most 12 months prior to inclusion. 3.c. Specific IgE ≥0.7 kU/L against at least one of the following major allergens: Der p 1, Der p 2 or Der p 23. performed at most 12 months prior to the inclusion visit. 3.d. Positive CFP to the mixture extract of the purified allergens Der p 1/Der p 2/Der p 23.
4. Asthmatic patients with a forced expiratory volume in the first second (FEV1) ≥ 80%.
5. Women of childbearing age should have a negative urine pregnancy test (childbearing is defined as from menarche to postmenopause, unless sterilized by hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) and be willing to use an effective method of contraception from 14 days before the first administration until 30 days after the last administration of the investigational drug.
6. Patients willing to comply with all study procedures, and have availability for follow-up for the duration of the study.

Exclusion criteria 24

1. Any total contraindication to treatment with allergen-specific immunotherapy or defined within the study according to the SmPC. In case of partial contraindication, the investigator will perform a personalized benefit/risk assessment.
2. Any total contraindication for SmPC. In case of partial contraindication, the investigator will perform a personalized assessment (e.g., chronic or infectious conjunctivitis/polyposis).
3. History of allergic reaction to any of the excipients present in the investigational product formulation.
4. Patients sensitized to epithelials (e.g. cat, dog, horse, mouse) who live with these animals or have frequent contact with them (direct or indirect)
5. Patients with clinically relevant sensitization to storage mites (mainly Lepidoglyphus destructor or Blomia tropicalis) at the investigator's discretion.
6. Patients with clinically relevant sensitization to fungi (mainly Alternaria alternata) at the investigator's discretion.
7. Use of other immunotherapy against D. pteronyssinus or other house dust mites (D. farinae) for more than one month in the last 5 years.
8. Current treatment with any type of immunotherapy with other allergens during the study period.
9. Current treatment or during the previous 16 weeks with any biological agent for allergic rhinoconjunctivitis and/or atopic dermatitis and/or any other non-allergic disease (dupilumab, benralizumab, mepolizumab, omalizumab, tezepelumab, among others).
10. Recent or anticipated nasal or paranasal surgery (e.g., polyposis) that may interfere with the trial, at the investigator's discretion
11. Moderate to severe atopic dermatitis.
12. Severe or uncontrolled asthma according to GINA 20245 guidelines or unstable asthma (i.e., clinically relevant exacerbations in the 3 months prior to inclusion), including a baseline FEV1<80%. NOTE: clinically relevant exacerbations are defined as any worsening of asthma requiring hospitalizations or emergency department visits and necessitating systemic corticosteroid therapy for ≥ 3 consecutive days, or any exacerbation requiring initiation or increase in baseline systemic corticosteroid intake for ≥ 3 consecutive days
13. Patients/legal representatives who decline to participate or do not sign informed consent or assent.
14. Pregnant or lactating women.
15. Severe uncontrolled systemic disease that poses a risk to participants, including but not limited to autoimmune, cardiovascular or hematologic disease, hyperthyroidism, clinically relevant liver or kidney disease, malignant tumors or chronic infection, severe unstable pulmonary disease as judged by a physician.
16. Contraindication to the use of adrenaline.
17. Active HIV infection
18. Active tuberculosis.
19. Dermographism, skin disease or skin disorders that interfere with the evaluation of skin tests.
20. Psychiatric disorder that prevents adequate compliance with the immunotherapy program.
21. Patients on current psychiatric treatment that interferes with diagnostic testing (e.g., tricyclic antidepressants). In case of needing psychiatric medication, this should not be withdrawn in order to be included in the study.
22. Concurrent participation in another clinical trial.
23. Non-cooperative attitude or non-compliance or taking medication to control allergic rhinitis/rhinoconjunctivitis symptoms other than that provided in this study.
24. Current drug or alcohol abuse or abuse during the previous year, or any substance abuse that may interfere with the trial in the investigator's discretion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Comparison of the required protein dose of Der p 1/ Der p 2/ Der p 23 extract, to trigger a positive CPP, performed at baseline, and after 12 maintenance doses comparing placebo with the 3 active treatment arms (Der p 1/Der p 2/Der p 23) at different doses.

Secondary endpoints 20

1. Change in combined symptom and medication score (CSMS1) from baseline and after 6 and 12 maintenance doses.
2. Change in symptom score (dSS) from baseline and after 6 and 12 maintenance doses.
3. Change in medication score (dMS) from baseline and after 6 and 12 maintenance doses.
4. Change in patient-reported visual analog scale (VAS) score on rhinoconjunctivitis and asthma symptoms (if applicable) (Appendix 7), from baseline and after 6 and 12 maintenance doses.
5. Change in severity of rhinitis and rhinoconjunctivitis as classified by the ARIA2 guideline (Appendix 8) from baseline and after 6 and 12 maintenance doses
6. Change in quality of life, according to the mini-RQLQ (Rhinoconjunctivitis Quality of Life Questionnaire3, Appendix 9), from baseline and after 6 and 12 maintenance doses
7. Change in lung function, according to forced expiratory volume in the first second (FEV1), from baseline and after 6 and 12 maintenance doses.
8. Percentage of patients showing improvement in CPP after 12 maintenance doses. To be considered an improvement, the concentration required to obtain a positive test after 12 doses must be higher (at least one dilution less) than that required at the baseline visit.
9. Degree of asthma control, according to the ACT questionnaire (Asthma Control Test4, Appendix 10), at baseline and after 6 and 12 maintenance doses.
10. Change in asthma severity, according to GINA guideline 20245 (Appendix 11), from baseline, after 6 and 12 maintenance doses.
11. Number of exacerbations defined as i. any worsening of asthma requiring hospitalizations or emergency department visits and necessitating systemic corticosteroid treatment for ≥ 3 consecutive days, or ii. any exacerbation requiring initiation or increase in baseline systemic corticosteroid intake for ≥ 3 consecutive days at baseline, after 6 and 12 maintenance doses. from baseline and after 6 and 12 maintenance doses.
12. Oral corticosteroid (CEO) consumption at baseline (during the previous year) and after 6 and 12 doses (since the previous visit). Measured as the number of cycles of at least 3 days of CEO.
13. IgE levels (total and specific: D. pteronyssinus, Der p 1, Der p 2, and Der p 23) at basal, after 6 doses and after 12 maintenance doses.
14. IgG4 levels (total and specific: D. pteronyssinus, Der p 1, Der p 2, and Der p 23) at baseline, after 6 doses and after 12 maintenance doses.
15. IgE/IgG4 ratio, at baseline, after 6 doses and after 12 maintenance doses.
16. Skin sensitization by prick test (intraepidermal skin test). Change in papule size after administration of D. pteronyssinus extract and Der p 1, Der p 2, and Der p 23 extracts at basal, after 6 doses and after 12 maintenance doses.
17. Severity/grade of systemic and local adverse reactions according to the 2010 World Allergy Organization (WAO, 2010) criteria6 (Appendix 12 and Appendix 13).
18. Percentage (%) of adverse reactions (ARs) per 100 administrations (injections).
19. Percentage (%) of patients with at least one AR per 100 administrations (injections)
20. Description of therapeutic measures for the management of ARs as well as their outcome.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Diater Laboratorio De Diagnostico Y Aplicaciones Terapeuticas S.A.

Sponsor organisation

Diater Laboratorio De Diagnostico Y Aplicaciones Terapeuticas S.A.

Address

Avenida De Gregorio Peces Barba 2

City

Leganes

Postcode

28919

Country

Spain

Scientific contact point

Organisation

Diater Laboratorio De Diagnostico Y Aplicaciones Terapeuticas S.A.

Contact name

Aida Gómez

Public contact point

Organisation

Diater Laboratorio De Diagnostico Y Aplicaciones Terapeuticas S.A.

Contact name

Aida Gómez

Third parties 1

Locations

1 EU/EEA country · 17 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 5 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