Multicenter clinical trial to evaluate efficacy and safety of sublingual immunotherapy in patients allergic to house mites, with rhinitis/rhinoconjunctivitis with or without mild to moderate asthma

Prior treatment

• Participants who have received previous immunotherapy to any of the tested allergen during the last 5 years or any desensitization process in the last 2 years (e.g., oral immunotherapy [OIT], milk, or egg) before the second screening visit (S2), or currently receiving immunotherapy with any other allergen
• Participants who have suffered chronic urticaria severe anaphylaxis, or with hereditary angioedema history within 2 years prior to first screening visit (S1)
• Participants who had a nasal surgery within 6 months prior to the first screening visit (S1) or have programmed or anticipated nasal surgery during the trial period
• Participants who required treatment with antihistamines and/or corticosteroids for other purposes than alleviating symptoms of allergic rhinitis (except temporal use for diseases such as common colds)
• Concurrent participation in other clinical trials or previous participation within 30 days prior to first screening visit (S1)
• Asthmatic participants with forced expiratory volume in the first second (FEV1) <80% (following at least a 6-hour washout of short-acting beta2 agonists [SABA] and 12-hour washout of long-acting beta2 agonists [LABA]) despite pharmacological treatment by the time of enrolment
• Participants with uncontrolled asthma, according to GINA 2022, asthma with poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma) and/or frequent exacerbations (≥2/year) requiring oral corticosteroids (OCS), or serious exacerbations (≥1/year) requiring hospitalization
• Participants on treatment with β-blockers or angiotensin-converting enzyme (ACE) inhibitor
• Participants on treatment with immunosuppressive or biological drugs
• Participants who had not had a long enough washout/withdrawal period at the first screening visit (S1) according to criteria in study protocol (See Table 6 in Section 9.5.3) before undergoing allergen diagnostic tests (skin prick test or IgE analysis)
• Unstable participants who have suffered a respiratory tract infection and/or asthma exacerbation within 4 weeks prior to the first screening visit (S1)

Other illness

• Participants having any contraindication for the use of adrenaline (e.g., hyperthyroidism, heart disease, or hypertension) according to the investigator’s criteria
• Participants with other severe diseases not related to allergic rhinitis or asthma that could interfere with the study treatment or the follow-up
• Participants with severe and unresponsive to treatment autoimmune diseases (e.g., thyroiditis or lupus), tumoral diseases or immunodeficiencies
• Participants that could not comply with the study protocol, according to the investigator's criteria, or have a serious mental illness
• Participants with known allergy to any of the components of the study treatment other than study allergens
• Participants who had a complication(s) of any nasal disease (including nasal polyp, nasal septal deviation, and hypertrophic rhinitis, drug-induced rhinitis and/or non-allergic rhinitis) affecting an appropriate evaluation of the efficacy and/or safety, according to investigator's criteria
• Those cases in which allergen-specific immunotherapy (AIT) would be a contraindication according to the criteria of European Allergy and Clinical Immunology Immunotherapy Subcommittee
• Participants with lower respiratory tract diseases different from asthma as emphysema, bronchiectasis or chronic obstructive pulmonary disease
• Participants with history of serious systemic reactions, including food, Hymenoptera venom, medications, etc.

Other

• Participants with a lesion in the oral cavity that could confound the safety profile of the study treatment, according to the investigator's criteria
• Breastfeeding or pregnant women
• Participants who are immediate family members of the investigator
• Participants expected to have marked changes (e.g, moving) in the circumstances of life during the study
• Participants who plan to start using anti-mite bedding or similar equipment during the study
• Participants who are considered inappropriate for the study, according to the investigator criteria
• Participants with severe asthma, according to GINA 2022,(2) on Step 4 or 5 treatment, who had poor symptom control and had good adherence and inhaler technique

• Participants who have signed and dated Informed Consent Form (ICF)
• Participants not sensitized to moulds, cockroach, Blomia tropicalis or other geographically relevant mites (negative skin prick test or IgE < 0.7 kU/L)
• Participants with a RCSMS ≥ 3 out of 6 recorded for at least 10 days in the baseline evaluation period, corresponding to moderate-to-severe allergic rhinitis /rhinoconjunctivitis
• Participants with specific IgE against a complete extract of D. pteronyssinus and / or D. farinae or any of the molecular components of allergenic sources with a value ≥ 3.5 kU/L
• Female or male aged 12 to 65 years, both included, at the time of signature of the ICF
• Participants with confirmed clinical history of inhalation allergy with intermittent or persistent moderate-severe rhinitis/ rhinoconjunctivitis according to the ARIA classification of at least 1 year of duration (treated with anti-allergic medication) with or without mild-moderate controlled intermittent or persistent asthma according to the definition of GINA 2022 caused by Dermatophagoides pteronyssinus and / or Dermatophagoides farinae).
• Participants with positive skin prick test and a wheal major diameter ≥ 5 mm to a standardized allergen extract of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae
• Women of childbearing age (i.e., following menarche and until postmenopause, defined as no menses for 12 months without an alternative medical cause, or non-subject to permanent sterilisation methods, such as hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must have a urine pregnancy test negative result before enrolling the study
• Women of childbearing age must commit to using an adequate contraception method
• Participants capable of complying with dosage regimen.
• Participants owning a smartphone to register symptoms and medication consumption
• Participants not sensitized to any other clinically relevant allergen or sensitized with the following characteristics (sensitization to other allergens will be assessed through skin prick test in Europe and LATAM and through IgE levels in China): a. Participants sensitized to dander (with a positive skin prick test for dander or IgE ≥ 0.35 kU/L), provided that they have occasional exposure and symptoms. b. Participants sensitized to endemic pollen (with a positive skin prick test or IgE ≥0.35 kU/L) will be scheduled to be included so that the pollen season does not coincide with the Baseline Evaluation Period nor with one month before and after the Main Evaluation Period. In LATAM, grass sensitized participants will not be included