Allergic Fungal Rhinosinusitis Clinical Trial
Official title:
A Randomized, 52-week Treatment Double-blind, Placebo-controlled Efficacy and Safety Study of Dupilumab 300 mg Every Other Week After Endoscopic Sinus Surgery in Patients With Allergic Fungal Rhinosinusitis (AFRS) on a Background Therapy With Intranasal Corticosteroid Spray
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.
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. Patients who meet the eligibility criteria will be enrolled in this randomized, double-blind study and will go through four periods. During the Run-in period, the subjects will receive saline irrigations at least daily for 2-6 weeks. Then subjects will undergo surgery per standard of care, and at this time, Sinonasal mucus, peripheral blood, and ethmoid tissue will be collected. After the surgery period, which lasts 4 weeks, subjects will be randomized to either Dupilumab or Placebo. Dupilumab (300 mg) and placebo will be given subcutaneously every other week for 52 weeks. This treatment period will be followed by a post-treatment period of 12 weeks. Dupilumab 300 mg will be administered subcutaneously (S)C every 2 weeks with an end of treatment (EOT) at week 52. A matching placebo will be administered subcutaneously (SC) at the same time points. Patients will receive a total of 26 doses of the investigational medical product (IMP). Patients 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. Self-administration of IMP will be completed at home to maintain a 2-week treatment schedule. All subjects will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Subjects will either receive fluticasone propionate or mometasone furoate. ;
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