Grass Pollen Immunotherapy Plus Dupilumab for Tolerance Induction

Inclusion Criteria

• Participant must be able to understand and provide informed consent
• A clinical history of grass pollen-induced allergic rhinoconjunctivitis for at least 2 years, with peak symptoms in May, June, or July
• A clinical history of moderate to severe rhinoconjunctivitis symptoms for at least 2 years, interfering with usual daily activities or with sleep as defined according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) classification of rhinitis
• A clinical history of inadequately controlled rhinoconjunctivitis symptoms, despite treatment with antihistamines and/or nasal corticosteroids during the grass pollen season, for at least 2 years
• Positive skin prick test response at screening, defined as wheal diameter ≥3 mm to Phleum pratense
• Positive specific immunoglobulin E (IgE) at screening, defined as IgE class 2 (e.g., ≥ 0.7 kilounits per liter [kU/L]) against Phleum pratense
• A woman of childbearing potential (WOCBP), regardless of birth control history, must:
• have a negative serum pregnancy test at screening,
• not be breast-feeding or lactating, and ---is required to consistently use one of the following highly effective methods of contraception throughout the study:
• hormonal (e.g. oral, transdermal, intravaginal, implant, or injection),
• intrauterine device (IUD) or system (IUS),
• vasectomized partner,
• bilateral tubal occlusion, or
• sexual abstinence.

Exclusion Criteria

• Inability or unwillingness of the Subject to give written informed consent or to comply with study protocol requirements
• Prebronchodilator forced expiratory volume (FEV1) 4 weeks per year, outside of the grass pollen season
• A clinical history of moderate to severe allergic rhinitis, as defined according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) classification of rhinitis, caused by either:
• An allergen to which the Subject is regularly exposed, or
• Tree pollen during tree pollen season, treated with regular antihistamine or intranasal corticosteroids
• History of emergency visit or hospital admission for asthma in the previous 12 months
• History of chronic obstructive pulmonary disease
• History of recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment
• History of chronic sinusitis, defined as a 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, and/or
• Ear pain, pressure, or fullness.
• History of systemic disease affecting the immune system, such as autoimmune diseases, immune complex disease or immunodeficiency
• At randomization: Current symptoms of, or treatment for:
• Upper respiratory tract infection,
• Acute sinusitis,
• Acute otitis media, or
• Other relevant infectious process ---Note: 1.) Serous otitis media is not an exclusion criterion and 2.) Participants may be re-evaluated for eligibility after symptoms resolve.
• A past history of any malignant disease in the previous 5 years
• Any tobacco smoking within the last 6 months, or a history of greater than or equal to 10 pack years of cigarette use.
• Any vaping or electronic cigarette use within the last 6 months
• Previous immunotherapy with grass pollen allergen within the previous 5 years
• Previous treatment by dupilumab (Dupixent®)
• Previous Grade 4 anaphylaxis (World Allergy Organization grading criteria), due to any cause
• History of anti-IgE, anti-IL-5, anti-IL-5 receptor, anti-IL-4/IL-13 receptor, or other monoclonal antibody treatment
• Use of tricyclic antidepressants or monoamine oxidase inhibitors
• Ongoing systemic immunosuppressive treatment
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