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

NCT04684524 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: EFC16724U1111-1246-75492020-002999-12
• Study Type: interventional
• Target: 62
• Locations: 9 countries
• Sites: 47

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 evaluate the efficacy of treatment with dupilumab to reduce sinus opacification in a population with allergic fungal rhinosinusitis (AFRS) at Week 24
• To assess the efficacy of dupilumab to reduce the need for rescue treatments
• To evaluate the efficacy of treatment with dupilumab in improving symptoms in AFRS
• To evaluate the efficacy of dupilumab to reduce nasal polyp formation in participants with AFRS
• To evaluate the efficacy of dupilumab in improving overall symptom severity and quality of life in AFRS
• To evaluate the efficacy of dupilumab in improving sense of smell in participants with AFRS
• To explore the effect of dupilumab as assessed by three-Dimensional CT volumetric measurement of the paranasal sinuses
• To evaluate the safety and tolerability of dupilumab when administered to participants with AFRS
• To evaluate the pharmacokinetics (PK) of dupilumab in participants with AFRS
• To characterize the effect of dupilumab on total IgE and specific IgE
• To assess immunogenicity to dupilumab in participants with AFRS

Conditions

Allergic Fungal Rhinosinusitis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 52 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score

  The LMK score is used to quantify the degree of opacification of each sinus on CT scan. The CT scan LMK staging system represents the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus plus the osteomeatal complex on each side). The extent of sinus opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the osteomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is 12 per side; total score ranges from 0 (normal) to 24 (more opacified) corresponding to the sum of all sinuses and the osteomeatal complexes bilaterally. Higher score indicate worse outcome; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

  Baseline (Day 1) and Week 52

Secondary Outcomes (22)

• Change From Baseline to Week 24 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary

  Baseline (Day -7 to Day -1) and Week 24

• Change From Baseline to Week 24 in Endoscopy Nasal Polyp Score (NPS)

  Baseline (Day 1) and Week 24

• Change From Baseline to Week 24 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score

  Baseline (Day 1) and Week 24

• Change From Baseline to Week 24 in Monthly Average Total Symptom Score (TSS) Derived From the Nasal Symptom Diary

  Baseline (Day -7 to Day -1) and Week 24

• Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT)

  Baseline (Day 1) and Week 24

Study Arms (2)

Dupilumab

EXPERIMENTAL

Dupilumab administered every 2 or 4 weeks based on weights

Drug: Dupilumab SAR231893

Matching placebo

PLACEBO COMPARATOR

Placebo administered every 2 or 4 weeks based on weights

Drug: Placebo

Interventions

Dupilumab SAR231893 DRUG

Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Dupilumab

Placebo DRUG

Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Matching placebo

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (47)

Asthma Allergy & Immunology Clinical Research Unit Site Number : 8400001

Tampa, Florida, 33613, United States

Location

Emory University Hospital Midtown Campus Site Number : 8400009

Atlanta, Georgia, 30308, United States

Location

Advanced ENT and Allergy Site Number : 8400004

Louisville, Kentucky, 40220, United States

Location

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

Mandeville, Louisiana, 70471, United States

Location

National Allergy and Asthma Research, LLC Site Number : 8400002

Charleston, South Carolina, 29407, United States

Location

Vanderbilt University Medical Center Site Number : 8400013

Nashville, Tennessee, 37232, United States

Location

REX Clinical Trials Site Number : 8400017

Beaumont, Texas, 77701-3713, United States

Location

Ut- Houston Medical School Site Number : 8400010

Houston, Texas, 77030, United States

Location

USA Clinical Trials Site Number : 8400020

San Antonio, Texas, 78229, United States

Location

Alamo ENT Associates Site Number : 8400018

San Antonio, Texas, 78258, United States

Location

Eastern Virginia Medical School (EVMS) Medical Group - Otola Site Number : 8400008

Norfolk, Virginia, 23507, United States

Location

Investigational Site Number : 0320003

CABA, Buenos Aires, C1414AIF, Argentina

Location

Investigational Site Number : 0320001

CABA, Buenos Aires, C1425BEN, Argentina

Location

Investigational Site Number : 0320005

Rosario, Santa Fe Province, 2000, Argentina

Location

Investigational Site Number : 0320002

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number : 0320004

Mendoza, 5500, Argentina

Location

Investigational Site Number : 1240001

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Investigational Site Number : 1560005

Beijing, 100050, China

Location

Investigational Site Number : 1560001

Beijing, 100730, China

Location

Investigational Site Number : 1560004

Changsha, 410013, China

Location

Investigational Site Number : 1560003

Chengdu, 610041, China

Location

Investigational Site Number : 1560013

Fuzhou, 350005, China

Location

Investigational Site Number : 1560006

Hangzhou, 310003, China

Location

Investigational Site Number : 1560012

Hefei, China

Location

Investigational Site Number : 1560002

Nanjing, 210029, China

Location

Investigational Site Number : 1560011

Qingdao, 266555, China

Location

Investigational Site Number : 1560009

Shanghai, 200030, China

Location

Investigational Site Number : 1560008

Taiyuan, 030001, China

Location

Investigational Site Number : 3560003

Coimbatore, 641028, India

Location

Investigational Site Number : 3560006

Jodhpur, 342005, India

Location

Investigational Site Number : 3560008

New Delhi, 110 062., India

Location

Investigational Site Number : 3760001

Petah Tikva, 49100, Israel

Location

Investigational Site Number : 3760002

Rehovot, 76100, Israel

Location

Investigational Site Number : 3920010

Isehara, Kanagawa, 2591193, Japan

Location

Investigational Site Number : 3920006

Shizuoka, Shizuoka, 420-0853, Japan

Location

Investigational Site Number : 3920008

Bunkyo-ku, Tokyo, 113-8431, Japan

Location

Investigational Site Number : 3920001

Meguro-ku, Tokyo, 153-8515, Japan

Location

Investigational Site Number : 3920003

Shinagawa-ku, Tokyo, 141-0001, Japan

Location

Investigational Site Number : 3920009

Shinjuku-ku, Tokyo, 160-8582, Japan

Location

Investigational Site Number : 6820002

Riyadh, 12713, Saudi Arabia

Location

Investigational Site Number : 6820001

Riyadh, 22252, Saudi Arabia

Location

Investigational Site Number : 7920004

Adana, 01380, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

Istanbul, 34093, Turkey (Türkiye)

Location

Investigational Site Number : 7920007

Istanbul, 34865, Turkey (Türkiye)

Location

Investigational Site Number : 7920006

Izmir, 35100, Turkey (Türkiye)

Location

Investigational Site Number : 7920003

Izmir, 35340, Turkey (Türkiye)

Location

Investigational Site Number : 7920005

Malatya, 44280, Turkey (Türkiye)

Location

Related Links

• EFC16724 Plain Language Results Summary

MeSH Terms

Conditions

Allergic Fungal Sinusitis

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Sinusitis; Paranasal Sinus Diseases; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: December 24, 2020
• Study Start: December 1, 2020
• Primary Completion: December 14, 2024
• Study Completion: March 7, 2025
• Last Updated: December 22, 2025
• Results First Posted: December 22, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

CN (11); US (11); SA (2); TU (6); AR (5); CA (1); IN (3); JP (6); IL (2)