Evaluation of Subcutaneous Immunotherapy with Der p 1/Der p 2/Der p 23 Allergens in Moderate/Severe Allergic Rhinitis/Rhinoconjunctivitis with/without Controlled Allergic Asthma
- Trial ID
- 2024-518519-20-01
- Protocol
- DIA-EC-MOLMite-01-24
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **benefit/risk balance** of three doses of subcutaneous immunotherapy (ITSC) with the main allergens of Dermatophagoides pteronyssinus, specifically Der p 1, Der p 2, and Der p 23, which are purified to determine the optimal dose after 12 maintenance doses. This is clinically relevant as it aims to establish the most effective and safe dosage for patients with moderate to severe allergic rhinitis or rhinoconjunctivitis, with or without controlled allergic asthma, due to sensitization to Dermatophagoides spp.
Secondary objectives include:
- Describing the sociodemographic and clinical profile of patients and its possible correlation with safety, efficacy, or immunologic outcomes.
- Evaluating the efficacy of three doses of ITSC by assessing changes from baseline after receiving 6 and 12 maintenance doses, focusing on global and specific efficacy variables for the entire population, including the asthmatic subpopulation.
- Assessing the percentage of patients who show improvement in the conjunctival provocation test after 6 and 12 maintenance doses.
- Evaluating the immune response against D. pteronyssinus and Der p 1/Der p 2/Der p 23 after administration of ITSC following 6 and 12 maintenance doses.
- Assessing the safety of three doses of ITSC with the major allergens of D. pteronyssinus, Der p 1/Der p 2/Der p 23 purified throughout the study.
Participants
The clinical trial involves participants diagnosed with **moderate to severe allergic rhinitis or rhinoconjunctivitis**, with or without controlled allergic asthma, due to sensitization to the Dermatophagoides genus. The study population includes both male and female subjects, aged between 12 and 65 years. Participants are required to have a clinical history of symptoms compatible with hypersensitivity to the Dermatophagoides genus, confirmed by a positive skin prick test and specific IgE levels against major allergens such as Der p 1, Der p 2, or Der p 23. Asthmatic participants must have a forced expiratory volume in the first second (FEV1) of at least 80%. Women of childbearing potential must have a negative urine pregnancy test and agree to use effective contraception. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are expected to comply with all study procedures and be available for follow-up throughout the study duration.
Plans and Procedures
The clinical trial is a **Phase II**, multicenter, double-blind, randomized, placebo-controlled, parallel-group study designed to evaluate the safety and clinical efficacy of subcutaneous immunotherapy with purified **Der p 1/Der p 2/Der p 23** allergens at different doses. The trial targets patients with moderate to severe allergic rhinitis or rhinoconjunctivitis, with or without controlled allergic asthma, due to sensitization to the **Dermatophagoides** genus. The primary objective is to assess the benefit-risk balance of three doses of immunotherapy to determine the optimal dose after 12 maintenance doses. The trial is expected to commence recruitment on February 17, 2025, and conclude by November 6, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, clinical history, and specific **IgE** levels. The trial will include follow-up visits after 6 and 12 maintenance doses to monitor changes in combined symptom and medication scores, lung function, and quality of life, among other secondary endpoints. The end-of-study visit will evaluate the overall efficacy and safety of the treatment, including the comparison of the required protein dose to trigger a positive **CPP** at baseline and after 12 maintenance doses.
The expected duration of participant involvement is approximately 53 weeks, during which they will receive subcutaneous injections of the investigational product. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of adverse reactions that necessitate discontinuation. The trial will adhere to rigorous methodological standards to ensure the reliability and validity of the findings, contributing valuable insights into the management of allergic rhinitis and rhinoconjunctivitis.
Treatment
The clinical trial involves the administration of **MOLMite**, a solution for skin-prick test, containing the active substance **Dermatophagoides pteronyssinus**. This experimental medication is formulated as a solution specifically designed for subcutaneous injection. The maximum daily dose is 0.8 ml, with a total maximum dose of 0.8 ml over a treatment period of 53 weeks. The administration route is subcutaneous injection, and the medication is provided by DIATER LABORATORIO DE DIAGNOSTICO Y APLICACIONES TERAPEUTICAS S.A. The active substance, Dermatophagoides pteronyssinus, is classified as a structurally diverse substance, specifically an allergen. The trial aims to evaluate the safety and clinical efficacy of subcutaneous immunotherapy with purified Der p 1/Der p 2/Der p 23 allergens at different doses in patients with moderate to severe allergic rhinitis/rhinoconjunctivitis, with or without controlled allergic asthma due to sensitization to Dermatophagoides spp.
In addition to the experimental treatment, a non-experimental treatment is used as a comparator in the study. This includes a solution containing **Hydróxido de Aluminio** at a concentration of 0.08 mg/ml, combined with a saline injectable solution (0.9%) and **Histamina** at 0.01 μg/ml. This comparator treatment does not have a specified pharmaceutical form or route of administration in the trial documentation. The role of this treatment in the trial is to serve as a placebo, allowing for a double-blind, randomized, placebo-controlled study design. The inclusion of this comparator is essential for evaluating the benefit/risk balance of the experimental treatment by providing a baseline for comparison.
Efficacy
Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint involves the comparison of the required protein dose of **Der p 1/Der p 2/Der p 23** extract to trigger a positive conjunctival provocation test (CPP) at baseline and after 12 maintenance doses, comparing placebo with the three active treatment arms at different doses. Secondary endpoints include changes in combined symptom and medication score (CSMS1), symptom score (dSS), and medication score (dMS) from baseline and after 6 and 12 maintenance doses. Additionally, changes in patient-reported visual analog scale (VAS) scores on rhinoconjunctivitis and asthma symptoms, severity of rhinitis and rhinoconjunctivitis as per ARIA guidelines, and quality of life according to the mini-RQLQ will be evaluated at the same timepoints.
Further assessments will include changes in lung function measured by forced expiratory volume in the first second (FEV1), percentage of patients showing improvement in CPP, degree of asthma control via the ACT questionnaire, and changes in asthma severity according to the GINA guideline. The number of exacerbations, oral corticosteroid consumption, and levels of IgE and IgG4 (total and specific to D. pteronyssinus, Der p 1, Der p 2, and Der p 23) will also be measured at baseline, after 6 doses, and after 12 maintenance doses. Skin sensitization will be evaluated by changes in papule size following administration of allergen extracts. The severity and grade of systemic and local adverse reactions will be assessed according to the 2010 World Allergy Organization criteria, along with the percentage of adverse reactions per 100 administrations and the percentage of patients with at least one adverse reaction per 100 administrations. Therapeutic measures for managing adverse reactions and their outcomes will also be documented.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients/legal representatives who have understood and signed the informed consent or assent form.
- Patients between 12 and 65 years of age, both inclusive.
- 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.
- Asthmatic patients with a forced expiratory volume in the first second (FEV1) ≥ 80%.
- 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.
- Patients willing to comply with all study procedures, and have availability for follow-up for the duration of the study.
Exclusion Criteria
- 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.
- Any total contraindication for SmPC. In case of partial contraindication, the investigator will perform a personalized assessment (e.g., chronic or infectious conjunctivitis/polyposis).
- History of allergic reaction to any of the excipients present in the investigational product formulation.
- Patients sensitized to epithelials (e.g. cat, dog, horse, mouse) who live with these animals or have frequent contact with them (direct or indirect)
- Patients with clinically relevant sensitization to storage mites (mainly Lepidoglyphus destructor or Blomia tropicalis) at the investigator's discretion.
- Patients with clinically relevant sensitization to fungi (mainly Alternaria alternata) at the investigator's discretion.
- Use of other immunotherapy against D. pteronyssinus or other house dust mites (D. farinae) for more than one month in the last 5 years.
- Current treatment with any type of immunotherapy with other allergens during the study period.
- 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).
- Recent or anticipated nasal or paranasal surgery (e.g., polyposis) that may interfere with the trial, at the investigator's discretion
- Moderate to severe atopic dermatitis.
- 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
- Patients/legal representatives who decline to participate or do not sign informed consent or assent.
- Pregnant or lactating women.
- 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.
- Contraindication to the use of adrenaline.
- Active HIV infection
- Active tuberculosis.
- Dermographism, skin disease or skin disorders that interfere with the evaluation of skin tests.
- Psychiatric disorder that prevents adequate compliance with the immunotherapy program.
- 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.
- Concurrent participation in another clinical trial.
- Non-cooperative attitude or non-compliance or taking medication to control allergic rhinitis/rhinoconjunctivitis symptoms other than that provided in this study.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 17 Feb 2025 | 160 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Hidróxido de Aluminio 0,08 mg/ml; Solución inyectable salina (0,9%) C.S.P: 1 ml and Histamina 0,01 μg/ml | Placebo | N/A | — | — | — | N/A |
MOLMite | Test | SOLUTION FOR SKIN-PRICK TEST | SUBCUTANEOUS INJECTION | 0.8 | 53 | PRD11663759 |