Evaluation of the Efficacy of Allergen-specific Immunotherapy Using Assessment in an Allergen Exposure chamber-a Randomized Placebo-controlled Double-blind Study

Exclusion Criteria

• •General criteria:
• •1. Patients are unable to understand and comply with the requirements of the trial, as judged by the investigator
• •2. Currently participating in another clinical trial or participating in any other clinical trial within 30 days prior informed consent for this trial
• •3. Low adherence to trial procedures expected or inability to understand instructions/trial documents
• •4. Involvement in the planning and conduct of the trial
• •5. Any relationship of dependence with the investigator
• •6. Previous randomization to treatment in the present trial
• •7. Mentally disabled
• •8. Institutionalized due to an official or judicial order For female patients with childbearing potential (i.e., females who are not chemically or surgically sterilized or females who are not post-menopausal)
• •9. Positive urine pregnancy test or pregnant
• •10. Wish to become pregnant during the course of the trial
• •11. Not using highly effective and reliable contraception, as judged by the investigator (reliable and highly effective methods of birth control defined as a failure rate of less than 1% per year \[CTFG recommendations 2020\]) during the trial. Sexual abstinence is an allowed method of birth control (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.) Males are not required to use any contraception during the study.
• •12. Wish to breastfeed or breastfeeding
• •Immunotherapy criteria:
• •13. History of a confirmed anaphylaxis after an AIT injection
• •14. Current treatment with any kind of AIT
• •15. AIT with HDM allergoids or allergens within the last 5 years
• •16. AIT with unknown allergen within the last 5 years Sensitization criteria
• •17. Clinically relevant symptoms to perennial and seasonal allergens which interfere with the assessment period of October to January. Exceptions are symptoms to allergens of cat and dog, if the patient has no direct contact to these animals.
• •Diseases and health status:
• •18. Clinically relevant chronic rhinoconjunctival or respiratory symptoms related to other reasons than allergy
• •19. Chronic persistent rhinitis symptoms for 20 years or longer
• •20. Forced expiratory volume in 1 second (FEV1) \< 70 % of predicted normal values according to Quanjer (Quanjer et al. 2012) under adequate asthma treatment according to GINA recommendation (GINA 2022)
• •21. Uncontrolled or partly controlled asthma according to GINA recommendation (GINA 2022)
• •22. Asthma exacerbation within the last 6 months prior to randomization defined as unscheduled doctors visit, hospitalization, or emergency unit visit requiring the use of systemic corticosteroids or change of controller medication
• •23. Severe acute or chronic diseases (e.g., COVID-19, chronic urticaria, mastocytosis, active tuberculosis, diabetes mellitus type I, malignant neoplasia, chronic renal failure), severe inflammatory diseases (liver, kidneys)
• •24. Autoimmune diseases, immune defects including immunosuppression, immune-complexinduced immunopathies (e.g., HIV, post-transplant patients, lupus erythematodes \[SLE\], vitiligo, Grave's disease, multiple sclerosis)
• •25. Severe psychiatric and psychological disorders including impairment of cooperation (e.g., alcohol or drug abuse)
• •26. Recurrent seizures (e.g., febrile convulsion, untreated epilepsy)
• •27. Irreversible secondary alterations of the reactive organ (e.g., emphysema, bronchiectasis)
• •28. For assessment the normal reference ranges of the central laboratory should be applied. If out of range, laboratory values greater than grade 1 according to the FDA Guidance for Industry (Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials) will lead to exclusion of the patient.
• •Medications:
• •29. Use of β-blockers (locally or systemically) and/or angiotensin-converting enzyme (ACE) inhibitors
• •30. Contraindication for use of adrenalin (e.g., acute, or chronic symptomatic coronary heart disease, severe hypertension)
• •31. Completion or ongoing treatment with anti-IgE-antibodies (e.g., omalizumab) or anti IL4/IL13 antibodies (e.g., dupilumab) or other biological medication interfering with the TH2 pathway
• •32. Completed or ongoing long-term treatment with tranquilizer or other psychoactive drugs