Clinical Trial to Evaluate the Efficacy and Safety of Polymerized, Mannan-Conjugated Dermatophagoides Allergen Extract

Prospective, Randomised, DBPC Clinical Trial to Evaluate the Efficacy and Safety of Polymerized and Mannan Conjugated Allergen Extract of Dermatophagoides for the Treatment of Allergic Rhinitis/Rhinoconjunctivitis With or Without Asthma

Prospective, randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of polymerized and mannan conjugated allergen extract of Dermatophagoides for the treatment of allergic rhinitis/rhinoconjunctivitis with or without asthma.

The main objective of the clinical trial is to evaluate the clinical efficacy of the investigational medicinal product, administered sublingually, compared to placebo for the treatment of moderate-severe rhinitis/rhinoconjunctivitis with or without mild to moderate asthma and controlled using the Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (R-CSMS).

Allergen-specific immunotherapy (AIT) has been shown to be effective in relieving symptoms, reducing medication use, and improving quality of life in patients with respiratory allergies). This is thought to be due to the induction of a state of tolerance to specific allergens with long-lasting effects after discontinuation of treatment. And it is accepted that immunotherapy is the only available method for allergists to improve or cure, partially or definitely, an allergic process The study population of this clinical trial will comprise subjects allergic to mites (Dermatophagoides pteronyssinus and/or D. farinae) with symptoms of moderate-severe rhinitis/rhinoconjunctivitis with or without mild to severe controlled asthma, suitable to allergen immunotherapy.

The primary efficacy endpoint will be the combined rhinitis/rhinoconjunctivitis symptom and medication score.

Every single day from the beginning of the administration of the investigational drug (V2-VF), the subject will be asked to score and register his/her symptoms and record medication consumption in an electronic diary following the instructions of the application. This diary will provide the symptom score and medication consumption for each subject during the trial.

Inclusion Criteria:

1. Signed Informed Consent Form.

2. Male or female, aged between 12 and 60 years, both included.

3. Confirmed clinical history of inhalation allergy with moderate-severe rhinitis/rhinoconjunctivitis according to the ARIA classification with or without controlled mild-moderate intermittent or persistent asthma according to the definition of GEMA 5.0 y GINA caused by allergy to mites (D. pteronyssinus and/or D. farinae). The asthma diagnostic will be valid up to 24 months prior to signing the informed consent form.

4. Combined Symptom and Medication Score for moderate to severe rhinitis/rhinoconjunctivitis (RCSMS) ≥ 1,8 out of 3.

5. Positive skin prick test (wheal major diameter ≥ 5 mm) to a standardized allergen extract of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. The results will be valid up to 12 months prior to signing the informed consent form.

6. Specific IgE against a complete extract of Dermatophagoides pteronyssinus and/or D. farinae or any the molecular components of allergenic sources with a value ≥ 3.5 kU/L. The results will be valid up to 12 months prior to signing the informed consent form.

7. Subjects shall preferably be monosensitised to the study allergens. In case of subjects sensitised to other aeroallergens, only those with the following characteristics may be included in the study (results will be valid up to 12 months prior to signing the informed consent form):

   • Subjects with a positive skin prick test to Blomia tropicalis and Lepidoglyphus destructor, whose wheal major diameter and specific IgE values do not exceed or equal the values for the study allergens.
   • Subjects with a positive skin prick test for dander if they have occasional exposure and symptoms.
   • Subjects with positive skin prick test to pollens, whose specific IgE values do not exceed or equal the values for the study allergens and who also do not have exacerbations during pollen season. The maximum specific IgE value to theses allergens is 17.5 kU/L.

8. Subjects with negative skin prick test to mold. In case specific IgE determination have been performed, the result must be <0.35 kU/L.

9. Women of childbearing age (since menarche) must present a negative urine pregnancy test at the time of trial enrollment.

10. Women of childbearing age must commit to using and adequate contraception method.

11. Subjects capable of complying with a dosage regimen.

12. Subjects owning a smartphone to register symptoms and medication consumption.

Exclusion Criteria:

1. Subjects polysensitized to other aeroallergens with clinically relevant symptoms.
2. Subjects who have received previous immunotherapy in the preceding 5 years to any of the tested allergens or a cross-reactive allergen or are currently receiving immunotherapy with any allergen.
3. Patients in whom immunotherapy may be subject to an absolute general contraindication according to the criteria of the Immunotherapy Committee of the Spanish Society of Allergy and Clinical Immunology and the European Allergy and Clinical Immunology Immunotherapy Subcommittee may not be included.
4. Subjects with uncontrolled severe asthma, and/or with FEV1 <80% of baseline despite adequate pharmacological treatment by the time of the enrolment.
5. Subjects on treatment with ß-blockers.
6. Subjects on treatment with immunosuppressive or biological drugs.
7. Subjects who are unstable by the time of enrolment (respiratory infection, febrile process, acute pruritus, etc.).
8. Subjects with chronic urticaria during the last 2 years, severe anaphylaxis or with hereditary angioedema history.
9. Subjects with any pathology in which the administration of adrenaline is contraindicating (hyperthyroidism, hypertension, heart disease, etc.) according to the investigator discretion.
10. Subjects with any other disease not related to moderate rhinoconjunctivitis or asthma, but potentially serious and that could interfere with treatment and follow-up (epilepsy, psychomotor disorders, diabetes, malformations, multi-surgery, nephropathy, etc.), according to the investigator discretion.
11. Subjects with severe autoimmune disease (thyroiditis, lupus, etc.), tumour diseases or diagnosed with immunodeficiencies.
12. Subject whose condition prevents him/her from offering cooperation and/or who presents severe psychiatric disorders, according to the investigator discretion.
13. Subjects with known allergy to the other components of the investigational product other than allergen study.
14. Subjects with lower airway diseases other than asthma such as emphysema or bronchiectasis.
15. Pregnant or breastfeeding women.
16. Subjects who are immediate family members of researchers.
17. Concurrent participation in other clinical trials or previous participation within 30 days prior to inclusion.
18. History of severe systemic reactions, including food, hymenoptera venom, etc.
19. Subjects who have suffered a respiratory tract infection and/or asthma exacerbation within 4 weeks prior to screening.
20. Subjects with a history of significant renal disease or chronic liver disease.