Dermatophagoides pteronyssinus allergens (Der p 1 / Der p 2 / Der p 23) for Allergic rhinitis | Allergic rhinoconjunctivitis | Allergic asthma

Inclusion criteria

• {"criterion_text":"- Patients/legal representatives who have understood and signed the informed consent or assent form.\n- Patients between 12 and 65 years of age, both inclusive.\n- 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: \t3.a. Clinical history with symptoms compatible with demonstrated hypersensitivity to the genus Dermatophagoides. \t3.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. \t3.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. \t3.d. Positive CFP to the mixture extract of the purified allergens Der p 1/Der p 2/Der p 23.\n- Asthmatic patients with a forced expiratory volume in the first second (FEV1) ≥ 80%.\n- 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.\n- Patients willing to comply with all study procedures, and have availability for follow-up for the duration of the study."}

Exclusion criteria

• {"criterion_text":"- 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.\n- Recent or anticipated nasal or paranasal surgery (e.g., polyposis) that may interfere with the trial, at the investigator's discretion\n- Moderate to severe atopic dermatitis.\n- 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\n- Patients/legal representatives who decline to participate or do not sign informed consent or assent.\n- Pregnant or lactating women.\n- 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.\n- Contraindication to the use of adrenaline.\n- Active HIV infection\n- Active tuberculosis.\n- Dermographism, skin disease or skin disorders that interfere with the evaluation of skin tests.\n- Any total contraindication for SmPC. In case of partial contraindication, the investigator will perform a personalized assessment (e.g., chronic or infectious conjunctivitis/polyposis).\n- Psychiatric disorder that prevents adequate compliance with the immunotherapy program.\n- 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.\n- Concurrent participation in another clinical trial.\n- Non-cooperative attitude or non-compliance or taking medication to control allergic rhinitis/rhinoconjunctivitis symptoms other than that provided in this study.\n- 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.\n- History of allergic reaction to any of the excipients present in the investigational product formulation.\n- Patients sensitized to epithelials (e.g. cat, dog, horse, mouse) who live with these animals or have frequent contact with them (direct or indirect)\n- Patients with clinically relevant sensitization to storage mites (mainly Lepidoglyphus destructor or Blomia tropicalis) at the investigator's discretion.\n- Patients with clinically relevant sensitization to fungi (mainly Alternaria alternata) at the investigator's discretion.\n- Use of other immunotherapy against D. pteronyssinus or other house dust mites (D. farinae) for more than one month in the last 5 years.\n- Current treatment with any type of immunotherapy with other allergens during the study period.\n- 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)."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measured as the protein dose required to trigger a positive conjunctival provocation test (CPP) at baseline and after 12 maintenance doses; comparison between placebo and the three active dose arms."}

Secondary endpoints

• {"endpoint_text":"- Change in combined symptom and medication score (CSMS1) from baseline and after 6 and 12 maintenance doses.","definition_or_measurement_approach":"Change from baseline measured after 6 and 12 maintenance doses using the CSMS1 score."}
• {"endpoint_text":"- Change in symptom score (dSS) from baseline and after 6 and 12 maintenance doses.","definition_or_measurement_approach":"Change from baseline measured after 6 and 12 maintenance doses using the dSS symptom score."}
• {"endpoint_text":"- Change in medication score (dMS) from baseline and after 6 and 12 maintenance doses.","definition_or_measurement_approach":"Change from baseline measured after 6 and 12 maintenance doses using the dMS medication score."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Patient-reported VAS for symptoms at baseline and after 6 and 12 maintenance doses."}
• {"endpoint_text":"- Change in severity of rhinitis and rhinoconjunctivitis as classified by the ARIA2 guideline (Appendix 8) from baseline and after 6 and 12 maintenance doses","definition_or_measurement_approach":"Change in ARIA2-classified severity from baseline measured after 6 and 12 maintenance doses."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change in mini-RQLQ score from baseline measured after 6 and 12 maintenance doses."}
• {"endpoint_text":"- Change in lung function, according to forced expiratory volume in the first second (FEV1), from baseline and after 6 and 12 maintenance doses.","definition_or_measurement_approach":"Change in FEV1 from baseline measured after 6 and 12 maintenance doses."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Proportion of patients whose CPP positive concentration after 12 maintenance doses is increased by at least one dilution compared to baseline."}
• {"endpoint_text":"- Degree of asthma control, according to the ACT questionnaire (Asthma Control Test4, Appendix 10), at baseline and after 6 and 12 maintenance doses.","definition_or_measurement_approach":"ACT questionnaire scores at baseline and after 6 and 12 maintenance doses to assess asthma control."}
• {"endpoint_text":"- Change in asthma severity, according to GINA guideline 20245 (Appendix 11), from baseline, after 6 and 12 maintenance doses.","definition_or_measurement_approach":"Change in asthma severity classification per GINA guidelines from baseline measured after 6 and 12 maintenance doses."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Count of exacerbations meeting specified criteria recorded at baseline and after 6 and 12 maintenance doses."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Number of oral corticosteroid cycles (≥3 days) at baseline and after 6 and 12 doses."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Laboratory measurement of total and specific IgE at baseline, after 6 doses and after 12 maintenance doses."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Laboratory measurement of total and specific IgG4 at baseline, after 6 doses and after 12 maintenance doses."}
• {"endpoint_text":"- IgE/IgG4 ratio, at baseline, after 6 doses and after 12 maintenance doses.","definition_or_measurement_approach":"Calculation of IgE/IgG4 ratio from measured antibody levels at specified timepoints."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measurement of change in skin prick test papule size for specified extracts at baseline and after 6 and 12 maintenance doses."}
• {"endpoint_text":"- Severity/grade of systemic and local adverse reactions according to the 2010 World Allergy Organization (WAO, 2010) criteria6 (Appendix 12 and Appendix 13).","definition_or_measurement_approach":"Grading of systemic and local adverse reactions per WAO 2010 criteria throughout the study."}
• {"endpoint_text":"- Percentage (%) of adverse reactions (ARs) per 100 administrations (injections).","definition_or_measurement_approach":"Rate of adverse reactions expressed as percentage per 100 administrations."}
• {"endpoint_text":"- Percentage (%) of patients with at least one AR per 100 administrations (injections)","definition_or_measurement_approach":"Proportion of patients with at least one adverse reaction per 100 administrations."}
• {"endpoint_text":"- Description of therapeutic measures for the management of ARs as well as their outcome.","definition_or_measurement_approach":"Descriptive reporting of treatments used to manage adverse reactions and outcomes."}

Spain

Earliest CTIS Part Ii Submission Date

15-01-2025

Latest Decision Or Authorization Date

01-09-2025

Processing Time Days

229

Number Of Sites

17

Number Of Participants

160

Primary sponsor

Full Name

Diater Laboratorio De Diagnostico Y Aplicaciones Terapeuticas S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Evidenze Health Espana S.L.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}