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

Asthma 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

Status Recruiting

Clinical Trial Summary

Background:

Allergic fungal rhinosinusitis (AFRS) is a severe type of sinus infection. People with AFRS develop heavy mucus and growths called polyps that apply pressure to the sinuses and block their breathing. Surgery can remove the polyps, but they often grow back. Researchers want to test an approved drug they believe may help people with AFRS.

Objective:

To test a drug (Dupilumab) in people with AFRS.

Eligibility:

People aged 18 years or older with suspected AFRS who are scheduled to undergo surgery for nasal polyps.

Design:

Participants will have several tests before their surgery. They will have imaging scans of their sinuses. They will have an endoscopic exam: A tube with a camera and a light will be inserted into their sinuses. They may give blood and mucus samples. They will have standard treatment with nasal sprays for 2 to 6 weeks before their surgery.

Excess nasal tissue removed during the surgery will be collected for research. Then they will begin treatment with the study drug.

Dupilumab is injected under the skin. Some participants will receive the study drug. Some will receive a placebo injections. The placebo injections are just like the study drug but contain no medicine. Participants will not know which injections they are getting.

All participants will administer the injections to themselves at home. They will do this every 2 weeks for 1 year after the surgery. They will have a clinic visit 16 weeks after surgery.

Participants will have follow-up for 12 weeks after treatment ends.

Clinical Trial Description

Study Description:

Multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of dupilumab to placebo in allergic fungal rhinosinusitis (AFRS) subjects after sinus surgery on a background treatment with intranasal corticosteroid spray.

Study periods:

The clinical trial consists of 4 periods:

-Run-in period (2 weeks + 4 weeks):

All participants will enter a run-in period of 2-6 weeks receiving saline irrigations and Intranasal Corticosteroids per the treating physician. All oral steroids and antibiotics will be stopped.

-Ethmoid Tissue Collection period (7 days + 4 weeks):

Participants will undergo surgery as scheduled per standard of care. Ethmoid tissue will be collected from all subjects at the time of surgery.

-Randomized treatment (52 weeks +/- 7 days):

Participants will be randomized to one of the following treatments:

• Arm A: dupilumab 300 mg subcutaneous (SC) every two weeks for 52 weeks

• Arm B: placebo given SC every two weeks for 52 weeks

• Posttreatment period (12 weeks +/- 7 days):

After completing 52 weeks of treatment with IMP (or following early discontinuation of IMP), subjects will be instructed to:

• Return to the study site for the last scheduled visits for physical examination, nasal endoscopy, Nasal Polyps Score (NPS), Patient-Reported Outcomes (PROs)(Sinonasal Outcomes Test-SNOT-22-, and Asthma Control Questionnaire -ACQ-), FEV1 measurement in those with asthma, and safety.

• Continue on stable dose of INCS spray during the posttreatment period.

• Report any adverse event (AE).

Co-Primary Objectives:

• Determine the efficacy of dupilumab in controlling sinonasal inflammation and preventing nasal polyp recurrence after complete sinus surgery for AFRS as measured by change in the mLK score.

• Evaluate the effect of dupilumab on oral corticosteroid utilization following complete sinus surgery for AFRS.

Secondary Objectives:

To evaluate the effect of dupilumab on:

• Prevention of revision surgery for AFRS

• Secondary objective measures of sinonasal inflammation following sinus surgery using NPS and LMS.

• Lower airway dysfunction following sinus surgery in the subgroup of participants with asthma (approximately 25%)

• Upper and lower airway, disease-specific, health-related quality of life, as measured by ACQ and SNOT-22

• Reducing utilization of rescue medications for acute exacerbations of CRS following sinus surgery

Primary Endpoints:

Change from baseline at 52 weeks both within and between treatment and placebo arms:

• Endoscopic modified Lund-Kennedy (mLK) score

• Incidence of oral corticosteroid utilization per participant

Secondary Endpoints:

Change from baseline at 52 weeks both within and between treatment and placebo arms:

• Prevalence of revision sinus surgery for recurrent nasal polyps, and comparison of survival curves

• Endoscopic nasal polyp score (NPS)

• CT generated Lund-McKay score

• Spirometry (for participants with comorbid asthma)

• 22-item sinonasal outcomes test (SNOT-22)

• Asthma Control Questionnaire (ACQ)

• Prevalence of oral / topical corticosteroid utilization per treatment cohort

• Incidence of oral / topical antibiotic utilization per subject

• Prevalence of oral / topical antibiotic utilization per treatment cohort ;

Related Conditions & MeSH terms

• Allergic Fungal Rhinosinusitis (AFRS)
• Allergic Fungal Sinusitis
• Asthma
• Nasal Polyps
• Rhinosinusitis
• Sinusitis

• NCT number: NCT06461949
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Susannah S Wargo, C.R.N.P.
• Phone: (301) 496-4887
• Email: susannah.wargo@nih.gov
• Status: Recruiting
• Phase: Phase 3
• Start date: June 26, 2024
• Completion date: March 1, 2026