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

• INCLUSION CRITERIA:

Participants are eligible for study participation if all inclusion and no exclusion criteria are met. Non- English-speaking people will be included if they fulfill the criteria. In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Informed consent

• Participants must be capable of giving signed informed consent as listed in theinformed consent form (ICF) and this protocol.

• ICF must be signed and dated prior to study specific procedures. Informed consentprocess 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 toundergo comprehensive sinus surgery per established criteria.

• Diagnosis of nasal polyps by consensus criteria.

• Failure of appropriate medical therapy, including topical intranasalcorticosteroid (spray or irrigation) > 8 weeks duration, systemiccorticosteroid trial of 1-3 weeks duration and nasal saline irrigation of > 4weeks 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 sexualpartner, tubal occlusion, intrauterine device or levonorgestrel Intrauterine system,Depo-Provera injections, oral contraceptive, Evra Patch, or Nuvaring. Women ofchildbearing potential must agree to use a highly effective method of birth control,as defined above, from enrollment, throughout the study duration and for 12 weeksafter the last dose of IMP.

• To protect against possible side effects, men should not get a sexual partnerpregnant while taking the study drug and for 12 weeks after the last dose. Menshould agree on a method of birth control to use throughout the study.

EXCLUSION CRITERIA:

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 toenrollment.

• Participants with conditions or comorbid disease findings that preclude nasalendoscopy 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 clinicalefficacy, 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 theInvestigator, 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 systemiccorticosteroids 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 studyperiod

• Known helminth infection.

• Unable to tolerate sinonasal irrigations.

• Pregnancy, current lactation, or lack of effective contraception plan, as determinedby the site investigator.

Prior Concomitant Therapy

• Initiation of allergen immunotherapy within 3 months prior to randomization or aplan to begin therapy or change its dose during the study period.

• Immunosuppressive medication within 3 months prior to randomization and during thestudy period from randomization through EOS.

• Receipt of any marketed or investigational biologic products (monoclonal orpolyclonal antibody) within 6 months or 5 half-lives, whichever is longer, prior torandomization 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 islonger 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 astable 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 studyprocedures.

• Prior randomization in the present study.