Study of Dupilumab 300 mg Every Other Week After Endoscopic Sinus Surgery in Patients With Allergic Fungal Rhinosinusitis (AFRS) on a Background Therapy With Intranasal Corticosteroid Spray

Exclusion Criteria

• •Informed consent
• •Participants must be capable of giving signed informed consent as listed in the informed consent form (ICF) and this protocol.
• •ICF must be signed and dated prior to study specific procedures. Informed consent process is described further below.
• •Age
• •Participants aged \>=18 years at the time of signing the ICF.
• •Types of subject and disease characteristics
• •Participants with nasal polyps in the setting of suspected AFRS and electing to undergo comprehensive sinus surgery per established criteria.
• •* Diagnosis of nasal polyps by consensus criteria.
• •* Failure of appropriate medical therapy, including topical intranasal corticosteroid (spray or irrigation) \> 8 weeks duration, systemic corticosteroid trial of 1-3 weeks duration and nasal saline irrigation of \> 4 weeks duration.
• •* A minimum SNOT-22 score of 20 at time of enrollment.
• •* A minimum CT Lund-MacKay score of \> 1 at time of enrollment.
• •Suspected AFRS based on Bent and Kuhn criteria
• •* Participants must meet 3/5 criteria at time of enrollment
• •* Environmental atopy by skin or serum testing
• •* Nasal polyposis
• •* Characteristic CT findings
• •* Eosinophilic mucous
• •* Fungal identification on histopathology
• •* Participants must meet 5/5 criteria at time of randomization.
• •Enrolled subjects are expected to undergo SoC allergy testing and sinus surgery prior to randomization. This will complete evaluation for suspected AFRS, thus enabling further study participation. Allergy testing \& sinus surgery, in addition to other SoC items, will be done per clinical guidelines at the treating institution and will not be covered in this protocol.
• •Sinus Surgery
• •All study participants will have met criteria for sinus surgery and undergo a comprehensive procedure prior to randomization. The procedure will not be assigned and will be completed per SoC at the treating institution for the management of nasal polyps in suspected AFRS.
• •Reproduction
• •Negative urine pregnancy test will be required at enrollment and study visits 3, 4, 5 and 6, throughout the treatment period for participants of childbearing potential (i.e., post-pubescent, premenopausal females).
• •Persons of childbearing potential must use an effective form of birth control (confirmed by the Investigator) e.g., total sexual abstinence, vasectomized sexual partner, tubal occlusion, intrauterine device or levonorgestrel Intrauterine system, Depo-Provera injections, oral contraceptive, Evra Patch, or Nuvaring. Women of childbearing potential must agree to use a highly effective method of birth control, as defined above, from enrollment, throughout the study duration and for 12 weeks after the last dose of IMP.
• •To protect against possible side effects, men should not get a sexual partner pregnant while taking the study drug and for 12 weeks after the last dose. Men should agree on a method of birth control to use throughout the study.
• •An individual who meets any of the following criteria will be excluded from participation in this study:
• •Medical Conditions:
• •Participants who have undergone nasal or sinus surgery within 3 months prior to enrollment.
• •Participants with conditions or comorbid disease findings that preclude nasal endoscopy for evaluation of primary outcome, such as:
• •* Current rhinitis medicamentosa
• •* Nasal cavity tumors
• •* Occlusive septal deviation following surgery
• •Clinically important comorbidities that may confound interpretation of clinical efficacy, including:
• •* Aspirin-exacerbated respiratory disease
• •* Cystic fibrosis
• •* Primary ciliary dyskinesia
• •* Hereditary Hemorrhagic Telangiectasia
• •* Antrochoanal polyposis
• •* Non-asthma eosinophilic disease, such as bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome
• •* Granulomatosis with polyangiitis
• •* Any corticosteroid dependent condition
• •A comorbid health disorder that is not medically controlled in the opinion of the Investigator, and has the potential to:
• •* Affect the safety of the subject throughout the study
• •* Impede the subject s ability to complete the duration of the study
• •* Influence the primary or secondary outcomes of the study
• •Participant experiencing a symptomatic asthma exacerbation requiring systemic corticosteroids or hospitalization (\>24 hours) within 4 weeks of randomization.
• •Infection requiring systemic antibiotics within 4 weeks of randomization.
• •--Parenteral and/or oral antibiotics associated with surgery are allowed
• •Medical contraindication to receiving dupilumab:
• •* Known hypersensitivity to dupilumab or any of its excipients
• •* Live vaccine administration within 30 days of randomization or during study period
• •* Known helminth infection.
• •Unable to tolerate sinonasal irrigations.
• •Pregnancy, current lactation, or lack of effective contraception plan, as determined by the site investigator.
• •Prior Concomitant Therapy
• •Initiation of allergen immunotherapy within 3 months prior to randomization or a plan to begin therapy or change its dose during the study period.
• •Immunosuppressive medication within 3 months prior to randomization and during the study period from randomization through EOS.
• •Receipt of any marketed or investigational biologic products (monoclonal or polyclonal antibody) within 6 months or 5 half-lives, whichever is longer, prior to randomization during the study period.
• •Previous use of dupilumab.
• •Receipt of immunoglobulin or blood products within 30 days prior to randomization.
• •Receipt of any investigational drug within 30 days or 5 half-lives, whichever is longer prior to randomization.
• •Scheduled systemic corticosteroid treatment during the study period:
• •--Standardized corticosteroid taper associated with planned surgery is allowed.
• •Receipt of leukotriene antagonists or modifiers for participants who were not on a stable dose for \> 30 days prior to randomization
• •Prior/concurrent clinical study experience
• •Concurrent enrollment in another investigational drug trial during the study period.
• •Other Exclusions
• •Participant involvement in the planning or conduct of the study.
• •Investigator assessment that the subject is unlikely to comply with study procedures.
• •Prior randomization in the present study.