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

Allergic fungal rhinosinusitis (AFRS) is a severe form of eosinophilic nasal polyposis with critically inadequate treatment options for the 10% of chronic rhinosinusitis subjects affected by the disease. Occlusive eosinophilic mucus and severe nasal polyposis present in early adulthood, with an unrelenting course marked by sinus expansion and pressure-induced dehiscence of the surrounding orbit and skull base. Despite appropriate therapies with oral/topical corticosteroids, saline irrigations, and comprehensive sinus surgery, nasal polyps aggressively recur, frequently within months of surgery. Medical options beyond topical and systemic steroids are limited. Neither antifungal nor allergen immunotherapy is beneficial. Due to persistent sinonasal inflammation, patients with AFRS receive an average of three corticosteroid bursts per year and revision sinus surgery every 42 months. 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. Patients who meet the eligibility criteria will be enrolled in this randomized, double-blind study and will go through four periods: a run-in period, surgery period, randomized treatment period, and post-treatment period. During the run-in period, patients will perform twice daily saline irrigations followed by intranasal corticosteroid spray (INCS) for 2 to 6 weeks before planned sinus surgery. Saline irrigations/INCS and sinus surgery will be completed by the standard of care (SoC). Patients who continue to meet eligibility criteria following surgery will be randomized to receive a placebo or dupilumab subcutaneously every 2 weeks. Participants will receive 26 doses of the investigational medical product (IMP), via either study personnel or home administration, to maintain a 2-week treatment schedule. Participants will receive IMP directly from the central pharmacy, with compliance assessments via reminder text messages on the day of each scheduled home administration, as well as monthly phone calls and injection device collection at recurring 3-month study visits. Participants will then be monitored on daily saline irrigation and INCS spray for 12 weeks to evaluate potential disease recurrence after discontinuation of IMP. An end-of-study visit will be conducted 12 weeks after the treatment period at Week 64.