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Trial registered on ANZCTR


Registration number
ACTRN12618000113257
Ethics application status
Approved
Date submitted
5/12/2017
Date registered
29/01/2018
Date last updated
24/03/2022
Date data sharing statement initially provided
12/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of mepolizumab in eosinophilic chronic rhinosinusitis
Scientific title
The effect of mepolizumab on patients with nasal polyp eosinophilia
Secondary ID [1] 293545 0
Nil known
Universal Trial Number (UTN)
U1111-1206-2066
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic rhinosinusitis 305759 0
Eosinophilic chronic rhinosinusitis 305760 0
Condition category
Condition code
Respiratory 304982 304982 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Mepolizumab 100mg subcutaneous injection will be administered by study investigators every 4 weeks for 6 months. Patients will be reviewed on every visit (every 4 weeks for 6 months) and 3 months following completion of therapy .
Intervention code [1] 299785 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304143 0
Histopathological eosinophilic count
Timepoint [1] 304143 0
Every 4 weeks for 6 months, then 3 months following treatment completion (primary endpoint).
Secondary outcome [1] 341089 0
Tissue biopsy of sinus mucosa and nasal polyp : features of eosinophil activation, degree of inflammation, degree of neutrophil infiltrate, basement membrane thickening and other tissue changes (this is a composite secondary outcome).
Timepoint [1] 341089 0
Every 8 weeks for 6 months, then 3 months following treatment completion
Secondary outcome [2] 341090 0
Blood eosinophil count and baseline serum blood markers of inflammation, including ESR, CRS, IgE, RAST.
Timepoint [2] 341090 0
Performed once at baseline visit with exception of blood eosinophil count (every 4 weeks).
Secondary outcome [3] 341091 0
Patient reported outcome measures : SNOT-22 to assess sino-nasal symptoms
Timepoint [3] 341091 0
Every 4 weeks from treatment commencement until treatment completion and once 3 months following treatment completion.
Secondary outcome [4] 341092 0
Fractional exhaled nitric oxide (FeNO) to be assessed using a NIOX VERO device.
Timepoint [4] 341092 0
Every 4 weeks from treatment commencement until treatment completion and once 3 months following treatment completion.
Secondary outcome [5] 341093 0
Nasal endoscopy: polyp size will be assess by recorded endoscopy
Timepoint [5] 341093 0
Every 4 weeks from treatment commencement until treatment completion and once 3 months following treatment completion.
Secondary outcome [6] 341434 0
Patient reported outcome measures: ACQ to assess asthma symptoms
Timepoint [6] 341434 0
Every 4 weeks from treatment commencement until treatment completion and once 3 months following treatment completion.
Secondary outcome [7] 380517 0
Smell function to be assessed using threshold and identification components of Sniffin Sticks test.
Timepoint [7] 380517 0
At baseline, week 12 week and week 24 .
Secondary outcome [8] 380518 0
Patient reported outcomes: smell questionnaire including "Individual Importance of Olfaction Questionnaire" and "Questionnaire for Olfactory Disorders".
Timepoint [8] 380518 0
At baseline, week 12 and week 24.

Eligibility
Key inclusion criteria
Adult patients with severe nasal polyp disease or eosinophilic chronic rhinosinusitis
Not currently receiving mepolizumab treatment
Patients who do not meet the PBS criteria for severe lower airway disease
Body weight: A minimum body weight >=40 kilograms (kg) at Visit 1
Gender: Male or female.
Informed consent: Capable of giving signed informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects with known hypersensitivity to mepolizumab
Subjects with other conditions that could lead to elevated eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic Esophagitis.
Subjects with known immunodeficiency
Subjects with cystic fibrosis

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Paired longitudinal assessment to assess treatment success/failure
Regression analysis to determine factors leading to treatment success/failure

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
29/05/2019
Actual
29/05/2019
Date of last participant enrolment
Anticipated
3/04/2020
Actual
6/03/2020
Date of last data collection
Anticipated
6/11/2020
Actual
18/11/2020
Sample size
Target
20
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 18250 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 298159 0
Charities/Societies/Foundations
Name [1] 298159 0
Rhinology and Skull Base Research trust fund
Country [1] 298159 0
Australia
Primary sponsor type
Individual
Name
Richard Harvey
Address
St Vincent's Centre for Applied Medical Research
67 Burton St, Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 297250 0
None
Name [1] 297250 0
Address [1] 297250 0
Country [1] 297250 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299174 0
St Vincent's Hospital Sydney Human Research Ethics Committee
Ethics committee address [1] 299174 0
St Vincent’s Hospital Translational Research Centre (Map)
97-105 Boundary Street
Darlinghurst NSW 2010
Ethics committee country [1] 299174 0
Australia
Date submitted for ethics approval [1] 299174 0
08/02/2018
Approval date [1] 299174 0
05/04/2018
Ethics approval number [1] 299174 0
SVH/18/025

Summary
Brief summary
The use of Mepolizumab has demonstrated success in the management of eosinophilic asthma. Anecdotal experience with mepolizumab in a well defined group of chronic rhinosinusitis patients with eosinophilic inflammation has been very positive. This study assesses the effect of mepolizumab in nasal polyp eosinophilia, in particular, aiming to demonstrate the effect of mepolizumab treatment of respiratory mucosal eosinophilic inflammation at the tissue level, in addition to the serum eosinophil level. This study aims to assess factors that may contribute to treatment success and failure including tissue histopathology, serum/blood biomarkers including blood eosinophils, assessment of recorded endoscopy and patient reported clinical improvement based on patient reported outcome measures.

This study would provide evidence of the direct tissue response to mepolizumab, provide a relationship between tissue and serum levels and might provide prognostic information to responders to therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79546 0
Prof Richard Harvey
Address 79546 0
St Vincent's Centre for Applied Medical Research
67 Burton St, Darlinghurst NSW 2010
Country 79546 0
Australia
Phone 79546 0
+61 2 9360 4811
Fax 79546 0
Email 79546 0
[email protected]
Contact person for public queries
Name 79547 0
Raquel Alvarado
Address 79547 0
St Vincent's Centre for Applied Medical Research
67 Burton St, Darlinghurst NSW 2010
Country 79547 0
Australia
Phone 79547 0
+61 2 9360 4811
Fax 79547 0
Email 79547 0
[email protected]
Contact person for scientific queries
Name 79548 0
Raquel Alvarado
Address 79548 0
St Vincent's Centre for Applied Medical Research
67 Burton St, Darlinghurst NSW 2010
Country 79548 0
Australia
Phone 79548 0
+61 2 9360 4811
Fax 79548 0
Email 79548 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1400Study protocol    374122-(Uploaded-19-02-2020-16-38-22)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseMepolizumab decreases tissue eosinophils while increasing type-2 cytokines in eosinophilic chronic rhinosinusitis.2022https://dx.doi.org/10.1111/cea.14152
N.B. These documents automatically identified may not have been verified by the study sponsor.