Allergen Challenge Trial of IRL201104 in Seasonal Allergic Rhinitis

Exclusion Criteria

• •1. A prebronchodilator forced expiry volume in 1 second (FEV1) less than 70% of the predicted value at the screening baseline visit.
• •2. Clinical history of persistent asthma requiring regular inhaled corticosteroids for \> 4 weeks per year outside of the grass pollen season.
• •3. Clinical history of moderate - severe allergic rhinitis, according to the ARIA classification, caused by a perennial allergen to which the participant is regularly exposed.
• •4. Clinical history of moderate-severe allergic rhinitis, according to the ARIA classification, caused by tree pollen (those with mild intermittent symptoms not requiring regular treatment may be included).
• •5. History of emergency visit or hospital admission for asthma in the previous 12 months.
• •6. History of chronic obstructive pulmonary disease.
• •7. History of significant recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment.
• •8. History of chronic sinusitis, defined as sinus symptoms lasting greater than 12 weeks that includes 2 or more major factors or 1 major factor and 2 minor factors. Major factors are defined as facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discolored postnasal discharge, purulence in nasal cavity, or impaired or loss of smell. Minor factors are defined as headache, fever, halitosis, fatigue, dental pain, cough, ear pain, pressure, or fullness.
• •9. History of systemic disease affecting the immune system such as autoimmune diseases, immune complex disease, or immunodeficiency.
• •10. At randomization, current symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process; serous otitis media is not an exclusion criterion. Participants may be re-evaluated for eligibility after symptoms resolve.
• •11. Active malignancy at randomization.
• •12. Any tobacco smoking within the last 6 months or a history of greater than or equal to 10 pack years.
• •13. Previous treatment by immunotherapy with grass pollen allergen within the previous 5 years.
• •14. History of bleeding disorders or treatment with anticoagulation therapy.
• •15. History of anti-IgE monoclonal antibody treatment.
• •16. Ongoing systemic immunosuppressive treatment.
• •17. History of intolerance to the study therapy, rescue medications, or their excipients.
• •18. Pregnant or lactating women. For women of childbearing potential, a positive serum or urine pregnancy test.
• •19. The use of any investigational drug within 30 days of the screening visit.
• •20. The presence of any medical condition that the investigator deems incompatible with participation in the study.
• •21. Moderate or severe renal impairment (eGFR \<60 mL/min/1.73 m2) or end stage renal disease.
• •23\. Known or suspected immunosuppression, including history of invasive opportunistic infections (eg, history of or active tuberculosis, non-tuberculous mycobacterial infections, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency, or prolonged infections suggesting an immunocompromised status, as judged by the investigator. 24. Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-study screening assessment that could interfere with the objectives of the study or the safety of the volunteer. 25. Clinical contraindication to intradermal challenge (IDC), skin prick test (SPT), skin prick titration (SPT), or nasal allergen challenge (NAC), to include:
• •1. Previous anaphylactic reaction to grass pollen or extract excipients
• •2. Acute inflammation of the nose or paranasal sinuses
• •3. Severe and uncontrolled bronchial asthma or chronic obstructive pulmonary disease
• •4. Systemic immunotherapy
• •5. A generalised dermatological condition rendering it impracticable to perform SPT or IDC on unaffected skin.
• •6. Severe dermatographism
• •7. Unable to cease antihistamines/other interfering drugs (i.e. antidepressants)
• •8. Concomitant use of beta-blockers