Mepolizumab and In-office Nasal Polypectomy in Patients With Chronic Rhinosinusitis (CRS). A Three Arm Study. (MELYSA)

This randomized, controlled multicenter trial will recruit patients aged 18 to 70 7 years with recurrent nasal polyposis requiring surgery and indication for biologic treatment according to EPOS 2020 guideline. Patients in the Mepolizumab arms will receive 100 mg of subcutaneous mepolizumab every 4 weeks for a total of 12 doses in addition to daily topical corticosteroid treatment.

All study procedures will be performed in five study visits and may take approximately 30 minutes. Clinical assessments include different questionnaires and nasal endoscopy. This trial includes three treatment arms.

1. Combined group (In-office nasal polypectomy group with mepolizumab): This group will undergone in-office nasal polypectomy and will receive Mepolizumab.
2. Medical group (mepolizumab): This group will receive Mepolizumab.
3. Surgical group (In-office nasal polypectomy): This group will undergone in-office nasal polypectomy. The main advantage is that it allows comparison of mepolizumab versus surgery and surgery/mepolizumab versus surgery + mepolizumab, providing more information on the most effective therapeutic approach.

The presence of adverse effects will be assessed in each treatment arm.

Study Overview

• Status: Not yet recruiting
• Conditions: Rhinosinusitis Chronic; Polyp, Nasal
• Intervention / Treatment: Drug: Mepolizumab; Procedure: Polypeptomy

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Bilbao, Spain
    • Hospital de Curces
    • Contact: Francisco Valcarcel
  • Jerez De La Frontera, Spain
    • Hospital de Jerez
    • Contact: Alfonso cuvillo
  • Madrid, Spain
    • Hospital Puerta del Hierro
    • Contact: Antonio Martinez
  • Oviedo, Spain
    • HUCA
    • Contact: Jose Luis Llorente
  • Santander, Spain, 39011
    • Hospital Universitario Marques de Valdecilla
    • Contact: david Lobo; Email: david.lobo@scsalud.es
  • Sevilla, Spain
    • Hospital Virgen Macarena
    • Contact: serafin sanchez
  • Valladolid, Spain
    • Hospital Valladolid
    • Contact: Jaime santos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant 18 years of age or older
• Patients with a diagnosis of CRS with polyposis according to the criteria of the EPOS2020 guideline:

Chronic rhinosinusitis with nasal polyps in adults is defined as presence of two or more symptoms, one of which should be either nasal blockage / obstruction / congestion or nasal discharge (anterior / posterior nasal drip); ± facial pain/pressure; ± reduction or loss of smell; for ≥12 weeks; and either endoscopic signs of nasal polyps, and/or CT changes: mucosal changes within the ostiomeatal complex and/or sinuses.

• Patients with indication for biologic treatment according to the criteria of the EPOS2020 guideline. Presence of bilateral polyps in a patient who had ESS (except in cases where the patient is not fit for surgery, see bellow) and three of the following criteria are required:
• Evidence of type 2 inflammation (tissue eos> 10/hpf* or blood eos>250, OR total IgE> 100).
• Need for systemic corticosteroids or contraindication to systemic steroids (≥ 2 courses per yr, OR long term (>3 months)
• Significantly impaired quality of life (SNOT ≥ 40)
• Significant loss of smell (≥7 VAS)
• Diagnosis of comorbid asthma
• Basal eosinophil count (BEC) ≥300 cells/μL for surgical naïve patients- only those not fit for surgery (major criteria) or for those who have had surgery and have recurrence (minor criteria).
• Patients have been informed and signed consent to participate in the study.
• For those patients not suitable for surgery, the criteria of the EUFOREA guidelines for indication of biological treatment will be used (4 criteria, one of them being ≥300 cells/μL BEC).

Exclusion Criteria:

• Any serious or uncontrolled systemic or psychiatric illness that prevents a correct cognitive or endoscopic assessment or does not advise participation in the study.
• Unilateral localized secondary CRS (odontogenic, fungal ball, tumor).
• Bilateral diffuse secondary CRS (cystic fibrosis; eosinophilic granulomatosis with polyangiitis-S. de Churg-Strauss-; granulomatosis with polyangiitis-S de Wegener-; primary ciliary dyskinesia; selective immunodeficiencies.
• Pregnancy/ breast feeding
• Hypersensitivity to mepolizumab or it's excipients
• Patients unable to complete the questionnaire or follow prescribed treatment.
• Patients who are participating in another clinical trial related to polyposis or asthma.
• Previously documented failure with IL-5/IL-5 receptor biologics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combined group; In-office nasal polypectomy group with mepolizumab	Drug: Mepolizumab; Patients in the Mepolizumab arms will receive 100 mg of subcutaneous mepolizumab every 4 weeks for a total of 12 doses in addition to daily topical corticosteroid treatment
Experimental: Medical group; (mepolizumab)	Drug: Mepolizumab; Patients in the Mepolizumab arms will receive 100 mg of subcutaneous mepolizumab every 4 weeks for a total of 12 doses in addition to daily topical corticosteroid treatment
Active Comparator: Surgical group; In-office nasal polypectomy	Procedure: Polypeptomy; This group will undergone in-office nasal polypectomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mepolizumab+polypectomy compared to mepolizumab or polypectomy, using the change from baseline in sinonasal outcome test (SNOT-22) total score	up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in nasal polyposis severity VAS score at 4 weeks, 6 months, 12 months		up to 52 weeks
Change in endoscopic nasal polyp score at 4 weeks, 6 months, 12 months		up to 52 weeks
Improvement in individual VAS symptoms (rhinorrhea, mucus in throat, nasal blockage, and sense of smell), patient-reported outcomes at 4 weeks, 6 months, 12 months		up to 52 weeks
Number of patients no longer requiring rescue systemic corticosteroid treatment throughout the first year after the first month of starting the study		up to 52 weeks
Number of participants with mepolizumab and in-office nasal polypectomy related adverse events		up to 52 weeks
Change from baseline in sinonasal outcome test	The minimum value is 0 and maximum value is 110	up to 4 and 24 week

Collaborators and Investigators

• Sponsor: Instituto de Investigación Marqués de Valdecilla

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 1, 2023
• First Submitted That Met QC Criteria: June 19, 2023
• First Posted (Actual): June 28, 2023

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 19, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Paranasal Sinus Diseases; Nose Diseases; Polyps; Sinusitis; Nasal Polyps
• Other Study ID Numbers: IDIVAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No