A Phase 4 interventional study of Mepolizumab in Chronic Rhinosinusitis With Nasal Polyps, sponsored by St. Paul's Sinus Centre. Not yet recruiting at 1 site in Canada. Open to participants aged 19 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-04-17.
Sponsored by St. Paul's Sinus Centre · Phase 4, Interventional, and Basic science
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.
Purpose:
CRS is a poorly understood disease with suboptimal therapeutic strategies and a high disease burden. Adaptive immunity in the form of Th2 polarized T cell responses and B cell IgE class switching, and plasma cell infiltration, are a core component of eosinophilic CRS and asthma, yet our understanding of adaptive immunity in CRS remains limited. Modulating the Th2 response, through IL-5 blockade, leads to mixed results for CRSwNP patients. There are a number of patients who achieve improved asthma control with IL-5 blockade therapies that fail to see the same improvements in their nasal disease, outlining the currently limited understanding of factors involved in disease activity, disease endotypes, and the effects of modulating the Th2 response in this tissue environment. Improved understanding of nasal tissue immunity modulation by IL-5 blockade at a cellular level is an essential step towards appropriate patient selection and development of new targeted therapeutics. Single-cell transcriptomics is powerful tool for characterizing tissue immune landscapes and functional variations, has as yet been poorly utilized beyond studies of nasal epithelium in CRS
Hypothesis
Objectives
Research design
The proposed study is a prospective experimental medicine study using IL-5 blockade as a way of investigating the effects of Th2 modulation on the generation of local tissue adaptive immunity in CRSwNP. Participants will be classified in:
This study involves three study visits for the Treatment arm (Baseline, weeks 6, and 30), two visits for disease control subjects, and one (Baseline) visit for Healthy control subjects.
Participants on study medication will receive 100mg of mepolizumab every 4 weeks subcutaneously.
Treatment Arm:
CRSwNP (NPS 1-8) and asthma undergoing IL-5 blockade (Mepolizumab)
o Nasal and blood samples Week 6 - Pre-Mepolizumab commencement (Pre-treatment) Week 30 - After Mepolizumab commencement (On treatment)
Control Arm:
Diseased Control:
CRSsNP without asthma
o Nasal and blood samples Week 6 - After 6 weeks standard of care therapy
Statistical analysis Single cell RNA sequencing data Sequenced data will be aligned with CellRanger v7.0. The resulting output files will be processed using a standard filtering and QC pipeline in Scanpy. The batch correction will be performed using scVI, and Leiden clustering will be performed. Cluster labels will be assigned using canonical marker genes and published gene signatures, with validation using a published dataset of sorted immune cells via the SingleR package. The downstream analysis will include, but not be limited to, gene set expression analysis (GSEA) of Hallmark and Gene Ontology genesets, differential abundance testing, weighted gene co-expression network analysis, and imputation of cell-cell interaction using CellphoneDB. TCR analysis will be performed using Scirpy, and BCR analysis with the Dandelion, and Immcantation suites
236 studies on the registry are indexed under Nasal Polyps; 68 are open to participants now.
This study's planned enrollment of 40 is below the median of 60 across 181 interventional studies indexed under Nasal Polyps.
Browse Nasal Polyps studies →St. Paul's Sinus Centre is the lead sponsor of 5 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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)
Disease control group:
Healthy controls:
Exclusion Criteria:
Participants are excluded from the trial if any of the following criteria apply:
Secondary, or suspected secondary, cause of nasal polyposis:
Have an acute or chronic infection (excluding that related to CRS) requiring management as follows:
Healthy controls exclusion criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
20 subjects with CRSwNP and asthma that will start Mepolizumab treatment
Drug: Mepolizumab
10 subjects with CRSsNP without asthma that will not start Mepolizumab and will continue their standard of care treatment.
10 healthy subjects without any sinuses disease
100mg of mepolizumab every 4 weeks subcutaneously for 6 months
Endotyping nasal response to Mepolizumab
Clinical response vs standard of care change in Endoscopic Nasal Polyp Score
Time frame: week 30
Endotyping nasal response to Mepolizumab
Clinical response vs standard of care change in SNOT-22 score
Time frame: week 30
Endotyping nasal response to Mepolizumab
Clinical response vs standard of care change in degree os eosinophil depletion
Time frame: week 30
Nasal immune endotyping
Comparison of Circulating B cells, Pre-IL-5 subjects, CRSsNP subjects, Healthy controls, Nasal vs NALT
Time frame: week 30
Start is estimated for Jun 2024; primary completion for Jan 2025, 7 months later.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Apr 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Mepolizumab
St. Paul's Sinus Centre