Stopping mepolizumab or dupilumab to see if nasal polyps stay in complete remission.

English Title: Complete Remission Study Subtitle: Discontinuation of Mepolizumab or Dupilumab After at Least 12 Months Without Symptoms in Patients With Severe Chronic Rhinosinusitis With Polyps - a National Danish RCT Study

This trial will test whether adults with well-controlled nasal polyps who have been on mepolizumab or dupilumab can safely stop the biologic and remain symptom-free.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Rigshospitalet, Denmark (Academic / other)
• Drugs / interventions: Dupilumab, Mepolizumab
• Locations: 6 sites (Copenhagen, Region H and 5 other locations)
• Trial ID: NCT07268313 on ClinicalTrials.gov

What this trial studies

This randomized, phase 4 study enrolls adults with chronic rhinosinusitis with nasal polyps who have been symptom-controlled on mepolizumab (Nucala) or dupilumab (Dupixent). Participants are randomized to either discontinue their biologic or continue as a control and are followed for one year with assessments at baseline and weeks 12, 26, 38, and 52, with the option to contact investigators if symptoms recur. The primary outcome is the proportion of patients who remain in complete remission after stopping treatment, and a secondary objective compares results between the two biologic drugs. The trial is conducted at three Danish centers following national guidance to attempt discontinuation in well-controlled patients.

Who should consider this trial

Good fit: Adults (≥18) currently on stable four-weekly mepolizumab 100 mg or dupilumab 300 mg, who met EPOS criteria including prior sinus surgery and have been symptom-controlled during the past year, are ideal candidates.

Not a fit: Patients with recent loss of control, ongoing significant sino-nasal symptoms, recent systemic steroid use, or those who did not meet the original EPOS entry criteria are unlikely to benefit from stopping treatment.

Why it matters

Potential benefit: If successful, some patients may be able to stop biologic injections without their polyps returning, reducing side effects and treatment costs.

How similar studies have performed: Some discontinuation studies in asthma suggest selected patients can stop biologics without relapse, but randomized evidence specifically for nasal polyps is limited.

Eligibility criteria

Inclusion Criteria:

5.1 Inclusion criteria (all must be fulfilled)

Inclusion criteria:

At the time when the patient started biological treatment, they must have fulfilled the EPOS criteria for initiation of biologic treatment (REF EPOS):

* Fulfil the criteria for CRSwNP
* Presence of bilateral polyps in a patient
* Had ESS (sinus surgery) (exceptional circumstances excluded)
* Fulfil at least three of the following five criteria Evidence of type 2 inflammation Need for (and treated with) systemic corticosteroids or contraindication to these SNOT-22 score of 40 or above Significant loss of smell Asthma needing regular inhaled corticosteroids

To enter this study, the patient must be:

* Above 18 years of age
* Currently be in treatment with either Dupilumab (300 mg) or Mepolizumab (100 mg) with treatment every fourth week. This treatment should have been stable/unchanged for at least three months.
* Within the latest year, the patient must at all times have scored all the below symptoms of CRS five or below on a VAS scale from 0 - 10 - Doing this, it is according to the EPOS defined as controlled disease. The items are: nasal blockage, rhinorrhea/postnasal drip, facial pain/pressure, smell, sleep disturbance or fatigue) Please view appendix 2.
* Within the latest year the nasal endoscopy cannot have showed polyp score of more than 1+1 out of 4+4, further, no thick secretions or general oedema must have been present.
* Within the latest year the patient is not allowed to have had ESS or rescue treatment for their CRSwNP (antibiotics or systemic steroids)
* The patient must be able to understand Danish and able to sign an informed content.

Exclusion Criteria:

* In the twelve months of remission the patient is not allowed to have had AECRS (acute exacerbation of chronic rhinosinusitis). A common cold is allowed.
* Polyp removal in the out-patient clinic may not have been performed within the last 3 months.
* In the twelve months of remission the patient cannot at any time have scored higher than 1.2 on the ACQ questionnaire, meaning that the patient does not have uncontrolled asthma (Appendix 3).
* 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 (asthma not included)
* Patients who are not able to give informed consent (i.e., patients who are permanently incapable)
* Patients who are not eligible because of the investigator's judgement
* Patients who experience pregnancy during the study will be excluded after an unscheduled visit (LOCF) - active IVF treatment. (Please look belove)
* Patients who have or recently have had illness, such as cancer that or its treatment is expected to significantly affect morbidity and/or quality of life in the next two years
* Unwillingness to follow the study procedure
* Hypersensitivity to any of either Dupilumab or Mepolizumab.

Where this trial is running

Copenhagen, Region H and 5 other locations

• Rigshospitalet — Copenhagen, Region H, Denmark (Recruiting)
• Nordsjællands hospital — Hillerød, Region H, Denmark (Recruiting)
• Køge øre næse hals afd — Køge, Region Sj, Denmark (Recruiting)
• Dept. of otorhinolaryngology, Odense — Odense, Region Syd, Denmark (Recruiting)
• Vejle sygehus — Vejle, Region S, Denmark (Recruiting)
• Gødstrup Hospital — Gødstrup, Denmark (Recruiting)

Study contacts

• Study coordinator: Kasper Aanæs, md, phd

Conditions Nasal Polyps