Identifying Predictors Of Response To Mepolizumab In CRSwNP

NCT05902325 | Recruiting Phase 4

• 1 other identifier: 2024-11343
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Keywords

CRSwNP; Epigenetic; Virus; Multiomics; Mepolizumab

Outcome Measures

Primary Outcomes (1)

• Persistent clinical response to mepolizumab after cessation off mepoluzimab treatment

  Percentage (%) of participants demonstrating persistent clinical response to mepolizumab following cessation of treatment will be defined as persistence of improvement in Nasal Polyp size greater than 1 six months after cessation of a twelve-month treatment course of mepoluzimab.

  18 months

Other Outcomes (5)

• Determine effect of mepolizumab on trafficking of individual immune and structural cell types present in the epithelium in CRSwNP

  6 months

• Effect on epithelial function in vitro

  6 months

• Effect on epithelial function in vivo

  6 months

Study Arms (1)

Mepolizumab 100mg injection

EXPERIMENTAL

Mepolizumab 100mg SC once every 4 weeks for 48 weeks (twelve injections)

Drug: Mepolizumab 100 MG Injection

Interventions

Mepolizumab 100 MG Injection DRUG

Patients will receive Mepolizumab 100mg SC once every 4 weeks for 48 weeks (twelve injections, no placebo) at the hospital. The IMP will be administered following clinic procedures and blood collection. Patients will be monitored at the study site for at least 30 minutes after injections for signs of hypersensitivity reaction. Subcutaneous injection sites should be alternated among the 4 quadrants of the abdomen (avoiding navel and waist areas) or the upper arms. Background therapy will be assured with mometasone furoate nasal spray (200µg BID) daily throughout the study.

Also known as: Nucala

Mepolizumab 100mg injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead

Study Sites (1)

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

Related Publications (3)

• Milavetz BI, Balakrishnan L. Viral epigenetics. Methods Mol Biol. 2015;1238:569-96. doi: 10.1007/978-1-4939-1804-1_30.

  PMID: 25421681 BACKGROUND

• Jiao J, Wang C, Zhang L. Epithelial physical barrier defects in chronic rhinosinusitis. Expert Rev Clin Immunol. 2019 Jun;15(6):679-688. doi: 10.1080/1744666X.2019.1601556. Epub 2019 Apr 9.

  PMID: 30925220 BACKGROUND

• Kim JY, Kim DK, Yu MS, Cha MJ, Yu SL, Kang J. Role of epigenetics in the pathogenesis of chronic rhinosinusitis with nasal polyps. Mol Med Rep. 2018 Jan;17(1):1219-1227. doi: 10.3892/mmr.2017.8001. Epub 2017 Nov 7.

  PMID: 29115522 BACKGROUND

MeSH Terms

Conditions

Virus Diseases

Interventions

mepolizumab; Injections

Condition Hierarchy (Ancestors)

Infections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Martin Yvon Desrosiers, MD

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Yvon Desrosiers, MD

CONTACT

514-890-8000; desrosiers_martin@hotmail.com

Leandra Mfuna Endam, Msc

CONTACT

514-890-8000; leandra.mfuna-endam.chum@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients with severe recurrent CRSwNP will receive Mepolizumab 100mg SC once every 4 weeks for 48 weeks (twelve injections, no placebo) at the hospital.

Study Record Dates

• First Submitted: May 11, 2023
• First Posted: June 15, 2023
• Study Start: October 3, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)