Add-on Dupilumab for AFRS as Postoperative Therapy (ADAPT)

NCT05545072 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: STUDY00000090
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to find a more effective treatment for allergic fungal rhinosinusitis (AFRS). Most people suffering from nasal polyps have elevated levels of white blood cells called eosinophils that are involved in inflammation of the air passages. Despite appropriate treatment with oral/topical corticosteroids, saline irrigations, and surgery, nasal polyps return frequently within months of surgery. Participants will be administered a placebo or dupilumab every two weeks for 52 weeks.

Conditions

Allergic Fungal Rhinosinusitis

Outcome Measures

Primary Outcomes (2)

• Modified Lund-Kennedy (mLK) Score

  The efficacy of dupilumab in controlling sinonasal inflammation and preventing nasal polyp recurrence after complete sinus surgery for allergic fungal rhinosinusitis (AFRS) is assessed by using the modified Lund-Kennedy score. The modified Lund-Kennedy score (mLK) is a validated measure of sinonasal inflammation, as evaluated by means of nasal endoscopy. The composite score ranges from 0 to 12, with an increasing score representing worsening inflammation among three separate findings (Nasal polyps, Discharge, Edema). Each finding is rated from 0 (absent) to 2 (severe). A ≥ 2-point increase from baseline total postoperative score represents a clinically significant worsening of sinonasal inflammation.

  Baseline and End of Treatment at Week 52

• Incidence of Oral/Topical Corticosteroid Utilization Per Participant

  The number of participants who, during study treatment and off-treatment follow-up, based on clinical evaluation, present worsening signs and/or symptoms and are started on oral corticosteroids rescue treatment.

  Baseline and End of Treatment at Week 52

Secondary Outcomes (13)

• Prevalence of Revision Sinus Surgery for Recurrent Nasal Polyps, and Comparison of Survival Curves

  Up to End of Treatment at Week 52

• Endoscopic Nasal Polyp Score (NPS)

  Baseline and End of Treatment at Week 52

• Percent Predicted Forced Vital Capacity (%FVC) Following Sinus Surgery in the Subgroup of Participants With Asthma (~25%)

  Baseline and End of Treatment at Week 52

• Forced Expiratory Volume in 1 Second (FEV1) Following Sinus Surgery in the Subgroup of Participants With Asthma (~25%)

  Baseline and End of Treatment at Week 52

• Forced Vital Capacity (FVC) Following Sinus Surgery in the Subgroup of Participants With Asthma (~25%)

  Baseline and End of Treatment at Week 52

Study Arms (2)

Dupilumab

EXPERIMENTAL

Participants receiving dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS).

Drug: Dupilumab; Drug: Intranasal Corticosteroid Sprays (INCS)

Placebo

PLACEBO COMPARATOR

Participants receiving a placebo to match dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS).

Drug: Placebo; Drug: Intranasal Corticosteroid Sprays (INCS)

Interventions

Dupilumab DRUG

Dupilumab will be administered subcutaneously at a dose of 300 milligrams (mg) in a 2 milliliter (mL) solution every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses.

Also known as: Dupixent

Dupilumab

Placebo DRUG

A placebo to match dupilumab will be administered subcutaneously every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses.

Placebo

Intranasal Corticosteroid Sprays (INCS) DRUG

All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will continue throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.

Dupilumab; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent
• Patients aged \>18 years at the time of signing the informed consent form (ICF)
• Patients with nasal polyps in the setting of suspected AFRS and electing to undergo comprehensive sinus surgery per established criteria
• Diagnosis of nasal polyps by consensus criteria
• Failure of appropriate medical therapy, including topical intranasal corticosteroid (spray or irrigation) \> 8 weeks duration, systemic corticosteroid trial of 1-3 weeks duration, and nasal saline irrigation of \> 4 weeks duration
• A minimum SNOT-22 score of 20 at the time of enrollment
• A minimum CT Lund-MacKay score of \> 1 at the time of enrollment
• Suspected AFRS based on Bent and Kuhn criteria
• Patients meet 3/5 criteria at the time of enrollment and 5/5 criteria at time of randomization: environmental atopy by skin or serum testing, nasal polyposis, characteristic CT findings, eosinophilic mucous, fungal identification on histopathology

You may not qualify if:

• Patients who have undergone nasal or sinus surgery within 3 months prior to enrollment
• Patients with conditions or comorbid disease findings that exclude nasal endoscopy for evaluation of primary outcomes, such as current rhinitis medicamentosa, nasal cavity tumors, occlusive septal deviation following surgery
• Clinically important comorbidities that may confound the interpretation of clinical efficacy, 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 the Investigator, 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
• Patient experiencing a symptomatic asthma exacerbation requiring systemic corticosteroids 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 the study period, known helminth infection
• Unable to tolerate sinonasal irrigations
• Pregnancy, current lactation, or lack of effective contraception plan, as determined by the site investigator
• Initiation of allergen immunotherapy within 3 months prior to randomization or a plan to begin therapy or change its dose during the study period
• Immunosuppressive medication within 3 months prior to randomization and during the study period from randomization through the end of the study
• Receipt of any marketed or investigational biologic products (monoclonal or polyclonal antibody) within 6 months or 5 half-lives, whichever is longer, prior to randomization 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 is longer prior to randomization

Sponsors & Collaborators

• Emory University: lead
• Sanofi: collaborator

Study Sites (3)

Emory Hospital Midtown-Otolaryngology

Atlanta, Georgia, 30308, United States

Location

Ambulatory Surgery Center - Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

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: Thomas S Edwards, MD Assistant Professor, Rhinology and Skull Base Surgery Division
• Organization: Emory University

thomas.edwards@emory.edu

4045017710

Study Officials

• Joshua M Levy, MD, MPH, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blinded, placebo-controlled, parallel-group
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Professor

Study Record Dates

• First Submitted: August 31, 2022
• First Posted: September 19, 2022
• Study Start: October 26, 2023
• Primary Completion: July 10, 2024
• Study Completion: July 10, 2024
• Last Updated: May 8, 2025
• Results First Posted: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: The investigators will share de-identified data beginning 3 months and ending 5 years following article publication.
• Access Criteria: Proposals should be directed to joshua.levy2@emory.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third-party website.

Locations

US (3)