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

• Status: Not yet recruiting
• Trial end date: 2025-10-01
• Target enrollment: 0
• Participant gender: All

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.

Certain proteins made by the body called interleukins, appear to play a major role in the survival and activation of eosinophils. Antibodies are proteins naturally produced by your body that find foreign substances such as bacteria, fungi, viruses, and other substances that enter your body and make them inactive. Dupilumab is an antibody made in the laboratory that has been made to block specific interleukins from activating the eosinophils. This research is being done to find out if the medication dupilumab is effective and safe when used to treat patients with AFRS following recommended sinus surgery. Dupilumab is already approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis (CRSwNP); however, it is not approved to treat AFRS. Therefore its use in this study is considered experimental.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Emory University
• Collaborator: Sanofi
• Treatments: Antibodies, Monoclonal

Criteria

Inclusion Criteria:

• Capable of giving signed informed consent as listed in the informed consent form (ICF) and this protocol.

• Patients aged >18 years at the time of signing the 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-McKay score of > 1 at the time of enrollment.

• Suspected AFRS based on Bent and Kuhn criteria [10]

• Patients meet 3/5 criteria at the time of enrollment

• Environmental atopy by skin or serum testing

• Nasal polyposis

• Characteristic CT findings

• Eosinophilic mucous

• Fungal identification on histopathology

Exclusion Criteria:

• 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 interpretation of clinical efficacy, including Sinonasal mucocele, aspirin-exacerbated respiratory disease, cystic fibrosis, primary ciliary dyskinesia, Hereditary Hemorrhagic Telangiectasia, antro-choanal polyposis, non-asthma eosinophilic disease, such as bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndromeGranulomatosis 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

• 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 (EOS).

• 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.

• Scheduled systemic corticosteroid treatment during the study period (Standardized corticosteroid taper associated with planned surgery is allowed)

• Receipt of leukotriene antagonists or modifiers for subjects who were not on a stable dose for > 30 days prior to randomization.

• Concurrent enrollment in another investigational drug trial during the study period.

• Patient involvement in the planning or conduct of the study.

• Investigator assessment that the subject is unlikely to comply with study procedures.

• Prior randomization in the present study.

• Unable to undergo sinus surgery due to comorbid medical conditions.