Status:

COMPLETED

Dupilumab in Allergic Fungal Rhinosinusitis (AFRS) (LIBERTY-AFRS-AI)

Lead Sponsor:

Sanofi

Collaborating Sponsors:

Regeneron Pharmaceuticals

Conditions:

Allergic Fungal Rhinosinusitis

Eligibility:

All Genders

6+ years

Phase:

PHASE3

Brief Summary

Primary Objective: * To evaluate the efficacy of treatment with dupilumab to reduce sinus opacification in a population with allergic fungal rhinosinusitis (AFRS) Secondary Objectives: * To evaluat...

Detailed Description

The duration of study for each participant will include 2-4 weeks of screening period (2 additional weeks could be allowed), 52 weeks of randomized investigational medicinal product (IMP) intervention...

Eligibility Criteria

Inclusion

  • Participant must be at least 6 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 identified within 5 years prior to screening or at screening with or without positive fungal stain
  • AFRS patients with the following:
  • An endoscopic NPS of at least 2 out of 4 for unilateral polyps or 3 out of 8 for bilateral polyps at Visit 1 (central reading) and Visit 2 (local reading) and,
  • Sinus opacification in CT scan with an LMK score of 9 for patients with unilateral polyps or 12 for patients with bilateral polyps during screening period and,
  • Body weight ≥15 kg

Exclusion

  • 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.
  • Treatment with commercially available dupilumab within 12 months, participation in prior dupilumab clinical trial, or discontinued dupilumab use due to adverse event.
  • 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).
  • The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Key Trial Info

Start Date :

December 1 2020

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

March 7 2025

Estimated Enrollment :

62 Patients enrolled

Trial Details

Trial ID

NCT04684524

Start Date

December 1 2020

End Date

March 7 2025

Last Update

December 22 2025

Active Locations (47)

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Page 1 of 12 (47 locations)

1

Asthma Allergy & Immunology Clinical Research Unit Site Number : 8400001

Tampa, Florida, United States, 33613

2

Emory University Hospital Midtown Campus Site Number : 8400009

Atlanta, Georgia, United States, 30308

3

Advanced ENT and Allergy Site Number : 8400004

Louisville, Kentucky, United States, 40220

4

South Louisiana Ear, Nose, Throat and Facial Plastic Surgery Site Number : 8400019

Mandeville, Louisiana, United States, 70471