The investigators will investigate the efficacy of dupilumab in patients with severe eosinophilic CRSsNP who are resistant to the conventional treatment with intranasal corticosteroids and have significantly extensive disease involving more than 2 sinuses bilaterally in sinus CT scan and Lund-Mackay sinus (LMK) CT score >=10 at baseline.

The investigators will use high blood eosinophils (>=200) as a biomarker for eosinophilic CRSsNP and investigate the efficacy of dupilumab in patients with severe eosinophilic CRSsNP who are resistant to the conventional treatment with intranasal corticosteroids and have significantly extensive disease involving more than 2 sinuses bilaterally in sinus CT scan and Lund-Mackay sinus (LMK) CT score >=10 at baseline. In addition, the investigators will have a prespecified enrollment goal of at least 50% of patients with type 2 inflammatory diseases such as asthma, allergic rhinitis, and/or atopic dermatitis on the basis of patient-reported history and will stratify subject numbers between dupilumab treatment and placebo group.

Inclusion Criteria:

• Age 18 or older
• LMK-CT score ≥ 10 (out of maximum of 24) at screening.
• Bilateral sinusitis with at least more than 2 sinus involvement despite completion of a prior intranasal corticosteroid (INCS) treatment for at least 8 weeks prior to screening
• Presence of at least two of the following symptoms prior to screening:
• Nasal blockage/obstruction/congestion
• Nasal discharge (anterior/posterior nasal drip)
• Facial pain/pressure
• Reduction or loss of smell
• Must have Eosinophilic CRSsNP (blood eos ≥ 200) within 6 months prior to screening
• Able and willing to undergo regular intervention as well as evaluation per study protocol
• Must agree not to participate in a clinical study involving another investigational drug or device throughout the duration of this study
• Must be competent to understand the information given in IRB approved ICF and must sign the form prior to the initiation of any study procedure

Exclusion Criteria:

• Age < 18

• With CRS with nasal polyps

• Treated in any clinical trial of dupilumab

• Has taken:

  1. Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc) within 2 months before screening or 5 half-lives, whichever is longer
  2. An experimental monoclonal antibody within five half-lives or within 6 months before screening if the half-life is unknown
  3. Anti-immunoglobulin E (IgE) therapy (omalizumab) within 130 days prior to screening
  4. Leukotriene antagonists/modifiers unless patient is on a continuous treatment for at least 30 days prior to screening
  5. Initiation of allergen immunotherapy within 3 months prior to screening or a plan to begin therapy or change its dose during the run-in period or the randomized treatment period

• Have had a sino-nasal surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS

• Patients with conditions/concomitant diseases making them non-evaluable at screening or for the primary efficacy endpoint such as:

  1. Antrochoanal polyps
  2. Nasal septal deviation that would occlude at least one nostril
  3. Acute sinusitis, nasal infection or upper respiratory infection at screening
  4. Ongoing rhinitis medicamentosa
  5. Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis
  6. Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis

• With co-morbid asthma are excluded if forced expiratory volume (FEV1) is 50% (of predicted normal) or less

• With known active bacterial, viral, fungal, mycobacterial infection, or other infection or any major episode of infection that required hospitalization or treatment with IV antibiotics within 30 days of screening or during screening or oral antibiotics within 14 days prior to screening. Fungal infection of nail beds is allowed

• Have human immunodeficiency virus/acquired immune deficiency syndrome

• Have acute or chronic hepatitis B/hepatitis C infection

• History of an opportunistic infection (eg, pneumocystis carinii, cryptococcal meningitis, progressive multifocal leukoencephalopathy) or serious bacterial, viral, or fungal infections (eg, disseminated herpes simplex, disseminated herpes zoster) and requiring IV medication(s) ≤ 3 weeks prior to randomization

• History of or currently active primary or secondary immunodeficiency

• History of cancer within the last 5 years, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved) or colonic mucosal dysplasia

• History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma

• History of alcohol or drug abuse within 1 year prior to randomization

• Receipt of live vaccine within 4 weeks prior to randomization

• Pregnant or breastfeeding

• Participation in another clinical study or treatment with an investigational drug or device

• Serious or active medical or psychiatric condition which, in the opinion of the Investigator, may interfere with treatment, assessment, or compliance with the protocol

Double-blinded