PollenVax Subcutaneous Immunotherapy for Mugwort Pollen-Induced Allergic Rhinitis

Inclusion Criteria:

1. Signed and dated written informed consent prior to any study-related procedures.
2. Age 18 to 65 years (inclusive) at the time of signing informed consent.
3. Ability and willingness to comply with all protocol requirements, including attendance at all scheduled visits, completion of study procedures, and maintenance of a patient diary.
4. Clinically significant symptoms of allergic rhinitis during the mugwort pollen season, for which allergen-specific immunotherapy (ASIT) is indicated in the investigator's judgment.
5. Diagnosis of allergic rhinitis as the primary condition caused by sensitization to mugwort pollen (Artemisia vulgaris), of moderate or severe intensity, with a duration of at least 2 years, per ARIA guidelines. Comorbid mild-to-moderate well-controlled bronchial asthma (per current GINA guidelines) is permitted (ICD-10: J30.1 and/or J45.0).

6. Confirmed sensitization to Artemisia vulgaris pollen and/or its major component Art v 1, established by at least one of the following:

   • Positive skin prick test (SPT) with wheal diameter ≥3 mm compared to negative control, with adequate positive control; co-sensitization to other inhalant allergens (including ragweed) is permitted provided the mugwort reaction is the largest wheal in the tested panel and corresponds to the seasonal pattern of symptoms; AND/OR
   • Specific IgE to the above allergens by ImmunoCAP: positive result (≥Class 1), i.e., above the positivity threshold per manufacturer instructions.
7. Physical examination findings (including body temperature, blood pressure, heart rate), laboratory and instrumental parameters without clinically significant abnormalities per investigator assessment.
8. Negative urine pregnancy test at screening (for women of childbearing potential).
9. Agreement to use adequate contraception from screening until 90 days after completion of study participation (for women of childbearing potential and their partners).
10. Participants who received placebo in the Phase I PollenVax study may be enrolled if they meet all inclusion criteria of this study and had no serious adverse events related to Phase I participation.

Exclusion Criteria:

1. Prior allergen-specific immunotherapy (ASIT) to Artemisia vulgaris pollen or any other allergen within the last 3 years.
2. Sensitization and clinically significant symptoms caused by another inhalant allergen that, per medical history and investigator's clinical assessment, dominate over mugwort-related symptoms and may substantially confound efficacy assessment during the observation period.

3. Severe or uncontrolled bronchial asthma, including any of the following:

   • Forced expiratory volume in 1 second (FEV1) < 70% of predicted value at screening;
   • Clinically significant asthma symptoms despite baseline therapy;
   • Asthma exacerbation requiring systemic corticosteroids, hospitalization, or emergency care within the last 6 months.
4. History of life-threatening allergic reactions (including anaphylaxis, airway edema, bronchospasm, Stevens-Johnson syndrome, Lyell syndrome) or any allergic reaction to allergen-specific immunotherapy.
5. Chronic or acute ENT disorders at screening that may substantially affect symptom assessment or safety of study participation, including active bacterial rhinosinusitis, severe polypous rhinosinusitis, or significant anatomical nasal obstruction requiring surgical treatment.
6. Immunoglobulin therapy within 6 months prior to screening or planned during the study period.
7. Treatment with biological agents targeting the immune system (including anti-IgE antibodies such as omalizumab, other monoclonal antibodies, or immune checkpoint inhibitors) within the last 12 months prior to screening or planned during the study.
8. Immune system disorders, including autoimmune diseases and primary or secondary immunodeficiencies, except well-controlled autoimmune thyroiditis and uncomplicated type 1 diabetes mellitus.
9. Severe acute or chronic inflammatory or infectious diseases in the active phase at screening.

10. Severe, decompensated, or unstable comorbid conditions, including but not limited to:

    • Severe chronic respiratory failure;
    • Liver cirrhosis Child-Pugh class B or C;
    • Unstable angina or clinically significant ischemic heart disease;
    • Chronic heart failure NYHA class III-IV or decompensated stage;
    • Uncontrolled arterial hypertension (systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg) despite treatment;
    • Clinically significant cardiac arrhythmias, including high-grade ventricular arrhythmias (Lown classification);
    • Myocardial infarction, acute stroke, transient ischemic attack, or pulmonary embolism within 6 months prior to Visit 0, or aortic aneurysm >6 cm;
    • Less than 3 months after coronary artery bypass grafting or coronary stenting;
    • Any other condition that, in the investigator's judgment, may affect patient safety or interpretation of study results;
    • Active malignancy of any location or malignancy within the last 5 years, except fully treated carcinoma in situ;
    • Severe renal failure;
    • Severe hepatic failure.
11. Serologically confirmed infection with HIV, hepatitis B, or hepatitis C virus.
12. Exacerbation of chronic allergic skin disease (including atopic dermatitis or generalized urticaria) at screening that may confound assessment of allergic symptoms.
13. Clinically significant abnormalities in routine laboratory tests per investigator assessment.
14. Alcohol, drug, or substance dependence within the past year per investigator assessment.
15. Pregnancy or breastfeeding.
16. Inability to discontinue beta-blocker therapy (systemic or topical) and/or presence of a condition where epinephrine use for anaphylaxis management is substantially limited per investigator's clinical assessment.
17. Use of immunosuppressive agents or other medications that cannot be discontinued during the study period and may affect patient safety or efficacy assessment.
18. Severe psychiatric or neurological disorders impairing the ability to provide informed consent or comply with protocol requirements.
19. Legal incapacity or limited legal capacity.
20. Factors indicating high risk of non-compliance with study procedures, including inability to attend regular visits, maintain a patient diary, or follow protocol requirements per investigator assessment.