Dupilumab for Prevention of Recurrence of CRSwNP After ESS

NCT04596189 | Completed Phase 4

• 1 other identifier: CE20.201
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Chronic rhinosinusitis with nasal polyps; Endoscopic sinus surgery; Dupilumab

Outcome Measures

Primary Outcomes (1)

• Number of participants with non-recurrence of sinus cavity oedema as assessed endoscopically

  As it is expected that during the trial period recurrences will remain limited to the confines of the ethmoid sinus cavity and will not extend beyond the middle turbinate, a measuring system capable of capturing oedema as a measure of early changes of polyp formation is required. To this end, a modified version of the Lund-Kennedy grading scale (LK) will be used to assess oedema of the post-ESS sinus cavity. Assessment of degree of oedema in patients where nasal polyps do not extend beyond the middle turbinate: 0= No oedema; 1= Mild oedema not obstructing visualisation of surface landmarks or visualisation of the accessory sinus ostia; 2= Oedema obstructing or preventing visualisation of the frontal or sphenoid sinus ostia but not completely filling the sinus cavity; 3= Oedema completely filling the sinus cavity but not extending beyond the middle turbinate.

  Baseline to Week 52

Secondary Outcomes (13)

• Percentage of participants with polyp recurrence outside the confines of the sinus cavity(ies)

  Baseline to Week 52

• Percentage of participants requiring a course of oral steroids for recurrence of nasal polyposis.

  Baseline to Week 52

• Percentage of participants requiring re-operation for recurrence of nasal polyposis

  Baseline to Week 52

• Difference in per-operative bleeding

  Week 0 (Day of surgery)

• Change in total nasal symptomatology

  Baseline to Week 52

Study Arms (2)

Dupilumab

EXPERIMENTAL

Sterile Dupilumab 150 mg/mL will be provided in pre-filled syringes (2.25 total volume) to deliver 300 mg in 2 mL.

Drug: Dupilumab 300 MG in 2 ML Prefilled Syringe; Drug: Mometasone Furoate nasal spray

Placebo

PLACEBO COMPARATOR

Sterile placebo for Dupilumab will be provided in identically matching pre-filled syringes to deliver 2 mL.

Other: Placebo; Drug: Mometasone Furoate nasal spray

Interventions

Dupilumab 300 MG in 2 ML Prefilled Syringe DRUG

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.

Also known as: Dupixent

Dupilumab

Placebo OTHER

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.

Placebo

Mometasone Furoate nasal spray DRUG

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.

Also known as: Nasonex

Dupilumab; Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years of age.
• Patients with bilateral sino-nasal polyposis scheduled for a revision surgery for CRSwNP, according to usual clinical criteria of untolerable obstruction, anosmia, recurrent infections or difficulty with control of asthma.
• Ongoing symptoms (for at least 8 weeks before V1).
• Signed written informed consent.

You may not qualify if:

• Patient who has previously been treated with Dupilumab studies
• Patient who has taken:
• Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc.) within 2 months before V1 or 5 half-lives, whichever is longer.
• Any experimental mAB within 5 half-lives or within 6 months before V1 if the half-life is unknown.
• Anti-immunoglobulin E therapy (omalizumab) within 130 days prior to V1.
• Patients who are receiving leukotriene antagonists/modifiers at V1 unless they are on a continuous treatment for at least 30 days prior to V1.
• Initiation of allergen immunotherapy within 3 months prior to V1 or a plan to begin therapy or change its dose during the run-in period or the randomized treatment period.
• Patients who have undergone any and/or sinus intranasal surgery (including polypectomy) within 6 months before V1.
• Patients who have had a sino-nasal surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS.
• Patients with conditions/concomitant diseases making them non evaluable at V1 or for the primary efficacy endpoint such as:
• Antrochoanal polyps.
• Nasal septal deviation that would occlude at least one nostril.
• Acute sinusitis, nasal infection or upper respiratory infection.
• Ongoing rhinitis medicamentosa.
• Underlying systemic disorders, including:

Sponsors & Collaborators

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

Study Sites (1)

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 1P1, Canada

Location

MeSH Terms

Interventions

dupilumab; Mometasone Furoate

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Martin Y Desrosiers, MD

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A placebo-controlled, double blind, prospective, real-world trial in patients with CRSwNP undergoing revision surgery for CRSwNP

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 22, 2020
• Study Start: May 25, 2021
• Primary Completion: April 23, 2024
• Study Completion: April 23, 2024
• Last Updated: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)