Identifying Predictors Of Long-Lasting Response To Mepolizumab In CRSwNP: Is The Disease-Modifying Role Secondary To Restored Anti-Viral Activity Or Enhanced Epithelial Regeneration?

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 4
SUMMARY

The investigators propose a real-world study to assess the mechanism of action of long-lasting response to mepolizumab in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and identify clinically useful predictors of response. Mepolizumab is a monoclonal antibody targeting IL-5 and is approved for use in asthma and CRSwNP. In clinical studies, 12 months of treatment with mepolizumab improved signs and symptoms of CRSwNP and reduced the need for surgery. While several biologic medications targeting facets of the Type 2 mechanism are currently indicated for chronic rhinosinusitis with nasal polyps mepolizumab alone appears capable of modifying the disease's biological behaviour and producing long-standing improvements after the cessation of treatment. In the mepolizumab for CRSwNP regulatory trial (SYNAPSE), a subset of patients experienced dramatic and long-lasting, which is over 48 months after cessation of administration of the investigational medicinal product (IMP) in our experience. This has been partially captured in a follow-on study to the registration trail, which showed that a subset of patients followed for 24 weeks after cessation of biologic therapy (with continued use of mometasone furoate) demonstrated persistent improvements over baseline. However, the mechanism of the long-lasting effect in a subset of patients is not well understood, and it is impossible currently to identify patients who will derive this maximal benefit. The mechanism for the prolonged improvements in CRSwNP seen in certain patients with mepolizumab remains to be established but suggests that effects beyond eosinophil trafficking are implicated. The investigators believe that mepolizumab has IL-5-mediated pleiotropic effects which contribute to disease modification with effects extending beyond eosinophil activation and trafficking. This may include the following primary or secondary effects: i) Improving epithelial barrier function ii) Altering mast cell dynamics iii) Reversing epigenetic modifications iv) Altering the immune response to better clear pathogenic bacteria or viruses.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Bilateral NP, as diagnosed by endoscopy or historical CT scan

• At least one NP surgery\* within the last 10 years.

• Severe NP symptoms consistent with a need for surgery (obstruction VAS symptom score\>5, overall, VAS symptom score \>7, endoscopic bilateral NP score ≥4 \[with a score ≥2 in each nasal cavity\]).

• Ongoing treatment with INCS (via spray or intranasal liquid steroid wash/douching) for ≥4 weeks prior to screening

• ≥2 of the following CRS symptoms for at least 12 weeks:

‣ Nasal blockage/obstruction/congestion

⁃ Nasal discharge (anterior/posterior nasal drip)

⁃ Facial pain/pressure

⁃ Reduction or loss of sense of smell

Locations
Other Locations
Canada
Centre Hospitalier de l'Université de Montréal (CHUM)
RECRUITING
Montreal
Contact Information
Primary
Martin Yvon Desrosiers, MD
desrosiers_martin@hotmail.com
514-890-8000
Backup
Leandra Mfuna Endam, Msc
leandra.mfuna-endam.chum@ssss.gouv.qc.ca
514-890-8000
Time Frame
Start Date: 2023-10-03
Estimated Completion Date: 2026-12-31
Participants
Target number of participants: 36
Treatments
Experimental: Mepolizumab 100mg injection
Mepolizumab 100mg SC once every 4 weeks for 48 weeks (twelve injections)
Sponsors
Leads: Centre hospitalier de l'Université de Montréal (CHUM)

This content was sourced from clinicaltrials.gov