th2 Modulation CRSwNP

NCT06107101 | Not Yet Recruiting Phase 4

• 1 other identifier: H23-01777
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic rhinosinusitis (CRS) is a condition of persistent sinonasal mucosal inflammation which affects 11.9% of the US population. Mepolizumab is newly approved to treat chronic rhinosinusitis with nasal polyps (CRSwNP, the spaces inside nose and head are swollen and inflamed) and acts booking interleukin-5 (IL-5) a protein implicated in the inflammatory process. We aim to use Single-cell RNA sequencing (RNA-Seq, a method of genetically 'barcoding' cells to allow gene expression to be profiled at the level of individual cells) to study the effects of IL-5 blockade on the generation and maintenance of nasal adaptive immune responses, in CRS subjects.

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Outcome Measures

Primary Outcomes (4)

• Endotyping nasal response to Mepolizumab

  Clinical response vs standard of care change in Endoscopic Nasal Polyp Score

  week 30

• Endotyping nasal response to Mepolizumab

  Clinical response vs standard of care change in SNOT-22 score

  week 30

• Endotyping nasal response to Mepolizumab

  Clinical response vs standard of care change in degree os eosinophil depletion

  week 30

• Nasal immune endotyping

  Comparison of Circulating B cells, Pre-IL-5 subjects, CRSsNP subjects, Healthy controls, Nasal vs NALT

  week 30

Study Arms (3)

Treatment

EXPERIMENTAL

20 subjects with CRSwNP and asthma that will start Mepolizumab treatment

Drug: Mepolizumab

Disease control group

NO INTERVENTION

10 subjects with CRSsNP without asthma that will not start Mepolizumab and will continue their standard of care treatment.

Control group

NO INTERVENTION

10 healthy subjects without any sinuses disease

Interventions

Mepolizumab DRUG

100mg of mepolizumab every 4 weeks subcutaneously for 6 months

Treatment

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be \>=19 of age at the time of signing the informed consent form.
• Capable of giving signed informed consent.
• Treatment group:
• Bilateral Chronic Rhinosinusitis with Nasal Polyposis and Asthma
• a. Diagnosis consistent with EPOS 2020 b. Endoscopic Nasal Polyps Score (1-8) c. Asthma diagnosis based on: i. Consistent Clinical symptoms (History of wheeze, cough and breathlessness) ii. Reversible airflow obstruction (Spirometry)
• Eligibility for Mepolizumab therapy (Canada)
• On waiting list for surgery with planned wait of \>6 months
• Disease control group:
• Bilateral Chronic Rhinosinusitis without Nasal Polyposis, (only for the disease control group) oDiagnosis consistent with EPOS 2020
• Healthy controls:
• Participants \>=19 of age and capable of giving signed informed consent
• Participants with no history of sinonasal or lower airway disease

You may not qualify if:

• Participants are excluded from the trial if any of the following criteria apply:
• Women who are pregnant, plan to become pregnant or breastfeed during the trial.
• Current participation in any other interventional treatment trials.
• Compliance: is unlikely to comply with trial visits based on investigator judgment.
• Secondary, or suspected secondary, cause of nasal polyposis:
• EGPA, positive MPO ANCA or circulating eosinophilia \>10% total leukocytes
• Known or suspected hereditary ciliary dysmotility (e.g: Cystic fibrosis, childhood-onset nasal polyposis)
• Diagnosed or suspected malignant or premalignant nasal disease (e.g: Schniderian Papilloma, unilateral nasal polyposis)
• Fungal rhinosinusitis (CT/Histology), positive Aspergillus skin prick testing and/or positive Aspergillus IgE RAST testing.
• Aspirin Exacerbated Respiratory Disease/Salicylate allergy
• Known hypersensitivity or significant allergies to monoclonal antibodies.
• Malignant neoplasm within 5 years (from screening) excluding basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterine cervix treated locally and without metastatic disease for 3 years.
• A history of a primary immunodeficiency.
• Active bleeding disorders, and/or inability to support interruption to anticoagulant or anti-platelet therapies for nasal biopsy.
• Severe nasal deformity precluding endoscopic assessment/biopsy of postnasal space

Sponsors & Collaborators

• St. Paul's Sinus Centre: lead

Study Sites (1)

St. Paul's Sinus Centre

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

MeSH Terms

Interventions

mepolizumab

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Model Details: * Treatment group:20 subjects with CRSwNP and asthma that will start Mepolizumab treatment * Disease control group: 10 subjects with CRSsNP without asthma that will not start Mepolizumab and will continue their standard of care treatment. * Control group: 10 healthy subjects without any sinus disease

Study Record Dates

• First Submitted: October 24, 2023
• First Posted: October 30, 2023
• Study Start: June 1, 2024
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: April 17, 2024

Record last verified: 2024-04

Locations

CA (1)