Phase III clinical trial to evaluate the efficacy and safety of specific immunotherapy with mannanconjugated allergoids for the treatment of rhinitis/rhinoconjunctivitis in patients allergic to house dust mites.

Prior treatment

• Use of drugs that could interfere with skin prick test reactions (e.g., antihistamines) within the deadlines set out in the protocol (See Section 9.2).
• Subjects who have received previous immunotherapy to allergens under study (D. pteronyssinus and D. farinae) during the last 5 years or currently receiving immunotherapy with any other allergen.
• Subjects who required regular treatment with antihistamines and/or corticosteroids (systemic – oral or injectable-, topical, cutaneous, or inhaled) for other purposes than alleviating symptoms of allergic rhinitis, except temporal use (≤ 15 days) for diseases including common colds.
• Concurrent participation in other clinical trials or previous participation within 30 days prior to the screening/baseline visit.
• Subjects who have undergone any desensitisation process (e.g., oral immunotherapy [OIT], milk, or egg) except those in the maintenance phase since at least 12 months.
• Unstable subjects who have suffered a respiratory tract infection and/or asthma exacerbation within 4 weeks prior to the screening/baseline visit.
• Subjects with uncontrolled asthma, according to GINA 2023(2),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.
• Asthmatic subjects with forced expiratory volume in the first second (FEV1) <80% despite pharmacological treatment. The result shall be valid up to 12 months prior to signing of informed consent (See Section 9.2).
• Subjects on treatment with β-blockers, except those administered topically, or angiotensin-converting enzyme (ACE) inhibitors.
• Subjects on treatment with immunosuppressive (not including corticosteroids), except those administered topically, or biological drug.
• Subjects requiring regular treatment with systemic corticosteroids (oral or injectable) for the treatment of rhinitis/rhinoconjunctivitis and asthma. The regular use of topical, cutaneous, or inhaled corticosteroids for the treatment of the pathologies mentioned above and atopic dermatitis is permitted.
• Subjects who have suffered chronic urticaria, severe anaphylaxis, or family history of angioedema within 2 years prior to the screening/baseline visit.

Other illness

• Subjects having any nasal condition (e.g., nasal polyp or non-allergic rhinitis) that could affect an appropriate evaluation of the efficacy and/or safety, according to investigator’s criteria.
• Subjects with history of serious systemic reactions, including food, Hymenoptera venom, drugs, etc.
• Those cases in which allergen-specific immunotherapy (AIT) would be a contraindication according to the criteria of European Allergy and Clinical Immunology Immunotherapy Subcommittee.(3)
• Subjects with controlled or uncontrolled cancer.
• Subjects having any contraindication for the use of adrenaline (e.g., hyperthyroidism, heart disease, or hypertension) according to the investigator’s criteria.
• Subjects with other severe disease not related asthma or rhinitis/rhinoconjunctivitis that could interfere in the study treatment or the follow-up (e.g., epilepsy or nephropathy) according to investigator’s criteria.
• Subjects with uncontrolled autoimmune diseases (e.g., thyroiditis or lupus), tumoral diseases, or immunodeficiencies.
• Subjects that could not comply with the study protocol, according to investigator’s criteria, or have a serious mental illness.
• Subjects with known allergy to any of the components of the investigational medicinal products (IMPs) other than study allergens.
• Subjects with lower respiratory tract diseases, different from asthma, as emphysema, bronchiectasis, or chronic obstructive pulmonary disease.

Other

• Subjects sensitised (positive skin prick test) to one or more pollens where the time interval between baseline visit (BV) and additional baseline visit (ABV) os more than 7 months.
• Breastfeeding or pregnant women.
• Subjects who are immediate family members of the investigator.
• Subjects with severe asthma, according to GINA 2023(2), on Step 4 or 5 treatment, who had poor symptom control and had good adherence and inhaler technique.

• Subjects who have signed and dated Informed Consent Form (ICF).
• Subjects capable of complying with dosage regimen.
• Subjects must record symptoms and medication consumption in an electronic diary via smartphone (preferably) or in a paper diary.
• To be confirmed at visit 1 (V1). Only subjects who meet the following criteria will be eligible for randomization: 12. Subjects with a rhinitis/rhinoconjunctivitis combined symptom and medication score (RCSMS) ≥ 2 out of 6, recorded for at least 10 days, corresponding to moderate-to-severe allergic rhinitis/rhinoconjunctivitis (See Section 6.2).
• Women of childbearing age must commit to using a highly effective contraception method during the trial and up to 1 months after the end of the investigational medicinal product. Such methods include combined (estrogen and progestogen containing) hormonal, contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), male condom, bilateral tubal occlusion, vasectomised partner, or sexual abstinence.
• Subjects capable of complying with dosage regimen.
• Subjects with negative skin prick test for moulds.
• Subjects must record symptoms and medication consumption in a n electronic diary (preferably) or in a paper diary.
• To be confirmed at visit 1 (V1) Only subjects who meet the following criteria will be eligible for randomization: Subjects with a rhinitis/rhinoconjunctivitis combined symptom and medication score (RCSMS) ≥ 2 out of 6, recorded for at least 10 days, corresponding to moderate-to-severe allergic rhinitis/rhinoconjunctivitis.
• Subjects with negative skin prick test for moulds.
• 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 confirm menarche and have a urine pregnancy test negative result before enrolling the study.
• Women of childbearing age must commit to using a highly effective contraception method during the trial and up to 1 months after the end of the investigational medicinal product. Such methods include combined (estrogen and progestogen containing) hormonal, contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), male condom, diaphragm used with spermicide, bilateral tubal occlusion, vasectomised partner, or sexual abstinence.