Dupilumab for Prevention of Recurrence of CRSwNP After ESS

Summary

The investigators believe that administering Dupilumab during the pre- and peri-operative period of surgery for chronic rhinosinusitis with nasal polyps (CRSwNP) will safely downregulate Type 2 inflammation of the healing sinus environment and will allow for better coordinated and more effective mucosal healing. Specifically, the investigators believe that endoscopic signs and symptoms of recurrence will be reduced in the Dupilumab-treated group, and that this will be reflected in quality of life (QOL). Additionally, by reducing Type 2 inflammation at the time of surgery, Dupilumab may offer an additional benefit by decreasing operative bleeding.

The investigators propose to perform a placebo-controlled, prospective, real-world trial in patients with CRSwNP undergoing revision surgery for CRSwNP to verify whether recurrences after endoscopic sinus surgery (ESS) can be prevented by controlling Type 2 inflammation during the peri-operative period using Dupilumab. A series of seven injections of Dupilumab (or placebo) will be administered to symptomatic patients undergoing ESS for CRSwNP. Beginning 4 weeks prior to surgery and continuing for 8 weeks post-surgery, q2 weekly injections will be administered to reduce Type 2 inflammation at time of ESS and during the post-operative recovery period.

Principal outcome will be absence of recurrence of mucosal oedema of the sinus cavity as assessed by endoscopy. Secondary objectives will assess Polyp size, sinus symptomatology, quality of life, smell and asthma control. Exploratory analyses will assess microbiome and gene expression profiles to better understand molecular mechanisms implicated in CRSwNP pathophysiology, and to identify the pathways implicated by modulation of Type 2 inflammation.

Conditions

• Chronic Rhinosinusitis With Nasal Polyps

Interventions

DRUG

Dupilumab 300 MG in 2 ML Prefilled Syringe

The Dupilumab will be administered following clinic procedures and blood collection. Patients will be monitored at the study site for at least 30 minutes after injections for signs of hypersensitivity reaction. Subcutaneous injection sites should be alternated among the 4 quadrants of the abdomen (avoiding navel and waist areas), the upper thighs or the upper arms, so that the same site is not injected twice consecutively. Injection in the upper arms could be done only by a trained person (caregiver trained by Investigator or Delegate) or health care professional but not the patients themselves.

OTHER

Placebo

The Placebo will be administered following clinic procedures and blood collection. Patients will be monitored at the study site for at least 30 minutes after injections for signs of hypersensitivity reaction. Subcutaneous injection sites should be alternated among the 4 quadrants of the abdomen (avoiding navel and waist areas), the upper thighs or the upper arms, so that the same site is not injected twice consecutively. Injection in the upper arms could be done only by a trained person (caregiver trained by Investigator or Delegate) or health care professional but not the patients themselves.

DRUG

Mometasone Furoate nasal spray

On a daily basis throughout the study, the patient will use a paper diary to record daily use of mometasone furoate nasal spray (MFNS) 50 μg/actuation nasal spray, suspension (refer to the package insert \& SmPC for a description, administration details and precautions for use). MFNS is provided in a bottle that contains 18 g (140 actuations) of product formulation. If patient is unable to tolerate 200 micrograms twice a day (total dose 400 micrograms) due to experiencing adverse event, patient may reduce dose to 200 micrograms once per day.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM)

  lead OTHER

Principal Investigators

• Martin Y Desrosiers, MD · Centre hospitalier de l'Université de Montréal (CHUM)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-05-25

Primary Completion

2024-04-23

Completion

2024-04-23

Countries

• Canada

Study Locations