Identifying predictors of response to mepolizumab in chronic rhinosinusitis with nasal polyps

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?

This study is testing how well mepolizumab works for people with chronic rhinosinusitis and nasal polyps who haven't had success with other treatments, to see what factors might predict their response to the medication.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM) (Academic / other)
• Drugs / interventions: Omalizumab, immunotherapy, mepolizumab
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT05902325 on ClinicalTrials.gov

What this trial studies

This study investigates the mechanisms behind the long-lasting effects of mepolizumab treatment in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). It aims to identify clinically useful predictors of response by employing a multiomic approach to analyze tissue samples before and after treatment. Thirty-six patients unresponsive to previous medical and surgical treatments will receive mepolizumab for twelve months, with their responses assessed through clinical parameters and sino-nasal endoscopy. The study is conducted in a real-world setting to better understand the disease-modifying effects of the treatment.

Who should consider this trial

Good fit: Ideal candidates include adults with severe chronic rhinosinusitis with nasal polyps who have not responded to prior medical or surgical interventions.

Not a fit: Patients with conditions such as cystic fibrosis or eosinophilic granulomatosis with polyangiitis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved personalized treatment strategies for patients with CRSwNP, enhancing their quality of life.

How similar studies have performed: Previous studies have shown promising results with mepolizumab in treating CRSwNP, indicating that this approach builds on established findings.

Eligibility criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* If as a result of a medical interview, physical examination, or screening investigation the physician responsible considers the participant unfit for the study.
* Cystic fibrosis
* Eosinophilic granulomatosis with polyangiitis (also known as Churg Strauss syndrome), Young's, Kartagener's or dyskinetic ciliary syndromes
* Antrochoanal polyps
* Nasal septal deviation occluding one nostril
* Acute sinusitis or upper respiratory tract infection (URTI) at screening or 2 weeks prior to screening
* Ongoing rhinitis medicamentosa (rebound or chemical-induced rhinitis)
* Participants who have undergone any intranasal and/or sinus surgery (for example polypectomy, balloon dilatation or nasal stent insertion) within 6 months prior to V1
* Participants where NP surgery is contraindicated in the opinion of the Investigator
* Participants with a known medical history of HIV infection.
* Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1.
* Participants who are currently receiving or have received within 3 months (or 5 half-lives - whatever is the longest) prior to the screening visit, radiotherapy, or investigational medications/therapies.
* Participants with a history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. Aspirin-sensitive participants are acceptable.
* Participants with a history of allergic reaction to anti-IL-5 or other monoclonal antibody therapy.
* Use of systemic corticosteroids (including oral corticosteroids) within 4 weeks prior to screening or planned use of such medications during the double-blind period
* Treatments with biological or immunosuppressive treatment (other than Xolair) treatment within 5 terminal phase half-lives of Visit 1
* Omalizumab (Xolair) treatment in the 130 days prior to Visit 1
* Commencement or change of dose of allergen immunotherapy within the previous 3 months.
* Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study. Contraceptive use will be required with a double barrier method or documented effective surgical sterilization.
* Immunocompromised subjects from disease or medication, other than oral corticosteroids.
* Women of childbearing potential (WOCBP) will be included with measures to prevent accidental exposure to IMP by using double barrier contraception and pregnancy test prior to injection.

Where this trial is running

Montreal, Quebec

• Centre Hospitalier de l'Université de Montréal (CHUM) — Montreal, Quebec, Canada (Recruiting)

Study contacts

• Principal investigator: Martin Yvon Desrosiers, MD — Centre hospitalier de l'Université de Montréal (CHUM)
• Study coordinator: Martin Yvon Desrosiers, MD

Conditions Chronic Rhinosinusitis With Nasal Polyps; CRSwNP; Epigenetic; Virus; Multiomics; Mepolizumab