Mepolizumab to CRSwNP Through 12 Months - Randomised to FESS and Non-FESS Within the First 2 Weeks

NCT05598814 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: 2022-ENT-FESS-nonFESS
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial will compare treatment in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma. The patients will be randomized to treatment with the biologic drug, Mepolizumab, or the biologic drug Mepolizumab combined with Functional Endoscopic Sinus Surgery (FESS). The aim of this study is to evaluate the effect of combined treatment with biologic treatment and surgery vs. biologic treatment only. The hypothesis is that surgical removal of polyps and inflamed tissue from the nasal sinuses will increase the effect of the biologic treatment, leading to a lower disease burden after 6 months of treatment, compared with biologic drugs only. Furthermore, combined biologics and surgery will keep a lower disease burden and better general health after 12 months of treatment than biologics alone. Inclusion criteria:

• Patients ≥ 18 years old at the time of signed informed consent (no upper limit)
• Patients who are referred to the outpatient clinic for the following reasons:
• Doctor's diagnosis of CRS
• NPS ≥ 2+2 out of a score of 8 (max)
• Severity measured as an SNOT22 score \> 35
• One FESS in general anaesthesia performed prior to inclusion (no time limitations)
• No course of systemic steroids within the last 3 months, whereas a daily low dose is allowed
• Possible doctor's diagnosis of asthma
• Type 2 inflammation Exclusion criteria:
• Patients who, because of language barriers, are not able to understand written information and, thus, are not able to answer questionnaires
• Patients who currently receive biologics for any other disease
• Patients who have previously or currently received biologics for CRS or asthma
• Patients who are not able to give informed consent (i.e., patients who are permanently incapable)
• Patients who meet ≥1 of the following:
• Malignant lung disease
• Cardiac disease of clinical importance
• Current pregnancy and breastfeeding, as well as planning to be pregnant in the near future
• Unwillingness to have FESS performed
• Patients needing FESS or systemic steroids (OCS) during the study period will be excluded after an unscheduled visit (last observation carried forward (LOCF))
• Patients who are not eligible because of the investigator's judgement The effect of the treatment will be evaluated with objective procedures and questionnaires related to CRSwNP and asthma after 3, 6 and 12 months.

Conditions

Chronic Rhinosinusitis with Nasal Polyps; Asthma

Outcome Measures

Primary Outcomes (1)

• Change in The Sino-Nasal Outcome Test 22 (SNOTT22) score

  The success rate indicated by a significant change in health-related quality of life related to nasal symptoms measured with the questionnaire SNOT22. The outcomes to be evaluated are the differences in success rates between the two treatment arms Minimum score = 0 and maximum score = 110 with high scores indicating a large rhinosinusitis-related health burden.

  6 months

Secondary Outcomes (23)

• Change in Vo2max/kg(Cardiopulmonary exercise test )

  6 and 12 motnhs folow-up

• Change in Daily step count

  6 and 12 months follow up

• Change in Activity level(questionnaire)

  6 and 12 months follow up

• Change in Nasal Polyp Score (NPS)

  3 and 6 months follow up

• Change in Forced Expired Volume in the first second (FEV1)

  6 and 12 months follow up

Study Arms (2)

Intervention group - FESS

EXPERIMENTAL

Biologic treatment with Mepolizumab and functional endoscopic sinus surgery (FESS).

Biological: Mepolizumab Injection; Procedure: Functional Endoscopic Sinus Surgery (FESS).

Control group - No-FESS

ACTIVE COMPARATOR

Biologic treatment with Mepolizumab

Biological: Mepolizumab Injection

Interventions

Mepolizumab Injection BIOLOGICAL

All patients in both the intervention group and the control group will be treated with Mepolizumab injections every month.

Control group - No-FESS; Intervention group - FESS

Functional Endoscopic Sinus Surgery (FESS). PROCEDURE

The Functional Endoscopic Sinus Surgery will be performed 2 weeks after the first injection of Mepolizumab in the intervention group.

Intervention group - FESS

Eligibility Criteria

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

You may qualify if:

• Patients ≥ 18 years old at the time of signed informed consent (no upper limit)
• Patients who are referred to the outpatient clinic for the following reasons:
• Doctor's diagnosis of CRS
• NPS ≥ 2+2 out of a score of 8 (max)
• Severity measured as an SNOT22 score \> 35
• No course of systemic steroids within the last 3 months, whereas a daily low dose is allowed
• Possible doctor's diagnosis of asthma
• Type 2 inflammation

You may not qualify if:

• Patients who, because of language barriers, are not able to understand written information and, thus, are not able to answer questionnaires
• Patients who currently receive biologics for any other disease
• Patients who have previously or currently received biologics for CRS or asthma
• Patients who are not able to give informed consent (i.e., patients who are permanently incapable)
• Patients who meet ≥1 of the following:
• Malignant lung disease
• Cardiac disease of clinical importance
• Current pregnancy and breastfeeding, as well as planning to be pregnant in the near future
• Unwillingness to have FESS performed
• Patients needing FESS or systemic steroids (OCS) during the study period will be excluded after an unscheduled visit (last observation carried forward (LOCF))
• Patients who are not eligible because of the investigator's judgement

Sponsors & Collaborators

• Vibeke Backer: lead

Study Sites (1)

Rigshospitalet, Department of Otorhinolaryngology, Head and Neck Surgery & Audiology

Copenhagen, 2100, Denmark

Location

MeSH Terms

Conditions

Asthma

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Vibeke B Backer, Professor

  Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The Nasal Polyp Score (NPS) evaluation will be performed by a third surgeon (blinded evaluation) who will not know the results of the screening visit and FESS/non-FESS randomisation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Pulmonologist, MD, DMSc (PI)

Model Details: The study is a randomized clinical trial with two arms. Arm 1: Biologic treatment with Mepolizumab every month combined with Arm 2: Only biologic treatment with Mepolizumab every month combined with Functional Endoscopic Sinus Surgery (FESS) 2 weeks after the first injection of Mepolizumab.

Study Record Dates

• First Submitted: October 25, 2022
• First Posted: October 28, 2022
• Study Start: April 1, 2023
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2025
• Last Updated: March 30, 2025

Record last verified: 2024-11

Locations

DK (1)