Actively Recruiting
Identifying Predictors Of Response To Mepolizumab In CRSwNP
Led by Centre hospitalier de l'Université de Montréal (CHUM) · Updated on 2025-02-14
36
Participants Needed
1
Research Sites
169 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Identifying Predictors Of Response To Mepolizumab In CRSwNP
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Bilateral nasal polyps diagnosed by endoscopy or CT scan
- At least one nasal polyp surgery within the last 10 years
- Severe nasal polyp symptoms needing surgery (obstruction VAS score >5 overall, >7 for specific symptoms, bilateral endoscopic score 64 with 62 in each nasal cavity)
- Ongoing treatment with intranasal corticosteroids (spray or liquid) for at least 4 weeks before screening
- At least two of the following symptoms for 12 weeks or more: nasal blockage, nasal discharge, facial pain/pressure, or reduced/loss of sense of smell
You will not qualify if you...
- Considered unfit for the study by the responsible physician after medical interview or screening
- Diagnosis of cystic fibrosis
- Diagnosis of eosinophilic granulomatosis with polyangiitis, Young's, Kartagener's, or dyskinetic ciliary syndromes
- Presence of antrochoanal polyps
- Nasal septum deviation blocking one nostril
- Acute sinusitis or upper respiratory infection at or within 2 weeks before screening
- Ongoing rebound or chemical-induced rhinitis (rhinitis medicamentosa)
- Intranasal or sinus surgery within 6 months before Visit 1
- Nasal polyp surgery contraindicated by Investigator
- Known HIV infection
- Known parasitic infestation within 6 months before Visit 1
- Receiving or received radiotherapy or investigational medications/therapies within 3 months or 5 half-lives before screening
- History of sensitivity or allergy to study medications or components, except aspirin sensitivity
- History of allergic reaction to anti-IL-5 or monoclonal antibody therapy
- Use of systemic corticosteroids within 4 weeks before screening or planned use during double-blind period
- Use of biologic or immunosuppressive treatments (except Xolair) within 5 half-lives before Visit 1
- Omalizumab (Xolair) treatment within 130 days before Visit 1
- Start or change in allergen immunotherapy within 3 months before screening
- Pregnant, breastfeeding, or planning pregnancy during study without contraception
- Immunocompromised due to disease or medication other than oral corticosteroids
- Women of childbearing potential must use double barrier contraception and have a negative pregnancy test before injection
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, Canada, H2X 3E4
Actively Recruiting
Research Team
M
Martin Yvon Desrosiers, MD
CONTACT
L
Leandra Mfuna Endam, Msc
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here