Sanofi: Acute Fungal Rhinosinusitis

To evaluate the ability of dupilumab to reduce the need for rescue therapy with systemic corticosteroids (SCS) or surgery of AFRS in patients with AFRS who previously have had surgery for AFRS

Inclusion Criteria :

Participant must be at least 12 years of age (or the minimum legal age for adolescents in the country of the investigational site) at the time of signing the informed consent.

Participants with the diagnosis of AFRS adapted from criteria by Bent and Kuhn (meeting all):

  • IgE mediated inflammatory response to fungal hyphae (specific IgE serology or skin test) Evidence of sensitization to fungus by skin testing (at screening or documented historical positive skin test in the previous 12 months), or positive fungal-specific IgE in serum at screening.
  • Nasal polyposis confirmed by nasal endoscopy at screening.
  • Characteristic CT signs to be performed during screening period and can include any of the below signs as assessed by central reader:
    • hyperdensities
    • bony demineralization
    • bone erosion of sinus
  • Eosinophilic mucin/mucus without fungal invasion into sinus tissue (identified within 5 years prior to screening or at screening)
  • Positive fungal stain of sinus contents removed during surgery (identified within 5 years prior to screening or during endoscopy at screening).

AFRS patients with the following:

  • An endoscopic NPS of at least 3 out of a maximum score of 8 (either unilateral or bilateral polyps) at Visit 1 (central reading) and Visit 2 (local reading) and,
  • Bilateral sinus opacification in CT scan with an LMK score of at least 12 during screening period and

Prior sino-nasal surgery(ies) for AFRS.

Body weight ≥30 kg

Exclusion Criteria:

  • Patients with nasal conditions/concomitant nasal diseases making them non-evaluable at Visit 1 or for the primary efficacy
  • Nasal cavity malignant tumor and benign tumors.
  • Known of fungal invasion into sinus tissue.
  • Severe concomitant illness(es) that, in the investigator’s judgment, would adversely affect the patient’s participation in the study
  • Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
  • Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection
  • Known or suspected immunodeficiency
  • Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit 1 or during the screening period.
  • History of systemic hypersensitivity or anaphylaxis to dupilumab or any of its excipients.
  • Participation in prior dupilumab clinical study or have been treated with commercially available dupilumab.
  • Patients who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as Xhance™, during screening period.
  • Patients who are on intranasal corticosteroids (INCS) spray unless they have received stable dose for at least 4 weeks prior to Visit 1.
  • Patients who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit 1.
  • Patients who have taken:
    • Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to Visit 1
    • Any investigational mAb within 5 half-lives prior to Visit 1
    • Anti-IgE therapy (omalizumab) within 4 months prior to Visit 1.
  • Treatment with a live (attenuated) vaccine within 4 weeks prior to Visit 1
  • Leukotriene antagonists/modifiers unless patient is on a continuous treatment for at least 30 days prior to Visit 1.
  • Initiation of allergen immunotherapy within 3 months prior to Visit 1 or a plan to begin therapy or change its dose during the screening or treatment period.
  • Patients received SCS during screening period.
  • Either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to Screening Visit (Visit 1).

For more information please call 502.893.0159 and ask for Research