Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001333808
Ethics application status
Approved
Date submitted
12/07/2021
Date registered
5/10/2021
Date last updated
27/09/2022
Date data sharing statement initially provided
5/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Mepolizumab for treatment of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome - A pilot study
Scientific title
Efficacy of mepolizumab in management of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome relapses: a pilot study
Secondary ID [1] 304730 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome 322752 0
Condition category
Condition code
Inflammatory and Immune System 320342 320342 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The mode of administration: 100mg mepolizumab powder reconstituted in the vial with 1.2 mL of sterile water for injection administered subcutaneously.
The frequency of administration is once only at Weeks 0, 4, 8 & 12
Administration of the study treatment mepolizumab, will be performed by clinical study site staff at study visits as listed above.
Participants will be monitored for a total of 28 weeks post-treatment commencement and 8 weeks post completion of treatment.
Participants will be monitored for a total of 28 weeks post-treatment commencement
Intervention code [1] 321106 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328194 0
Number of flare up episodes of DRESS defined as an event where there is:
- A new organ involvement as assessed by accessing patient medical records, including blood test results and clinical findings,
- Deterioration in the previous organ involvement after a period of improvement or stabilisation as assessed by accessing patient medical records, including blood test results and clinical findings, OR
- Significant eosinophilia requiring increased dose of prednisone as assessed by accessing patient medical records.

Timepoint [1] 328194 0
Intervention will be administered at Weeks 0, 4, 8 & 12
Number of flare up episode of DRESS will be assessed at Weeks 2, 4, 8, 12, 16, 20 & 28 weeks.
The treatment will stop at week 12 but the participants will be monitored for further 16 weeks, at each time point outlined the above.
Primary outcome [2] 328195 0
Change dose of prednisone used during the course of the treatment assessed by accessing patient medical records.
Timepoint [2] 328195 0
28 weeks - this outcome will only be assessed once at 28 weeks post-treatment commencement.
Secondary outcome [1] 397988 0
DRESS syndrome remission defined as eosinophil count and CRP to return to normal range, resolution of the rash and stabilisation of the organ involvements as defined by kidney function and liver function tests on the blood tests.
Timepoint [1] 397988 0
Physical examination for rash and blood tests for other parameters will be performed at week 0, 2, 4, 8, 12, 16, 20 and 28 weeks.
Secondary outcome [2] 397990 0
Extent of skin damage assessed using VAS skin score
Timepoint [2] 397990 0
Physical examination for rash will be performed at week 0, 2, 4, 8, 12, 16, 20 and 28 weeks.
Secondary outcome [3] 397991 0
Time to complete cessation of prednisone without evidence of relapse, assessed by accessing patient medical records.
Timepoint [3] 397991 0
28 weeks - this outcome will only be assessed once at 28 weeks post-treatment commencement.
Secondary outcome [4] 400573 0
Extent of the organ damage assessed using electrolytes, liver function tests, full blood counts, ESR and CRP.
Timepoint [4] 400573 0
Physical examination and blood tests for organ damage will be performed at week 0, 2, 4, 8, 12, 16, 20 and 28 weeks.

Eligibility
Key inclusion criteria
Adult patients (18 years old and above) who are diagnosed with DRESS syndrome (based on the RegiSCAR criteria) and with eosinophil count >0.8 x 10^9/L.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
those with other eosinophilic disorders or concurrent parasitic infection, pregnant or breastfeeding patients, children and those who are unable to give informed consent.

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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Kaplan-Meier survival curve will be used for analysis and the study data will be compared to the retrospective data at the study sites. Small sample numbers will limit interpretation of statistical analyses. Nonetheless non-parametric methods will be used to compare study parameters between the two groups.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
29/09/2022
Actual
Date of last participant enrolment
Anticipated
31/01/2024
Actual
Date of last data collection
Anticipated
19/08/2024
Actual
Sample size
Target
8
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 20177 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 20178 0
Nepean Hospital - Kingswood
Recruitment hospital [3] 20179 0
The Alfred - Melbourne
Recruitment hospital [4] 20180 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [5] 20181 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 23216 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 34907 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 34908 0
2747 - Kingswood
Recruitment postcode(s) [3] 34909 0
3004 - Melbourne
Recruitment postcode(s) [4] 34910 0
2560 - Campbelltown
Recruitment postcode(s) [5] 34911 0
5000 - Adelaide
Recruitment postcode(s) [6] 38582 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 309104 0
Commercial sector/Industry
Name [1] 309104 0
Glaxo Smith Kline Research & Development Ltd
Country [1] 309104 0
United Kingdom
Funding source category [2] 309124 0
Charities/Societies/Foundations
Name [2] 309124 0
Balnaves Foundation
Country [2] 309124 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital, Sydney
Address
390 Victoria St
Darlinghurst
NSW 2010
Country
Australia
Secondary sponsor category [1] 310052 0
None
Name [1] 310052 0
Address [1] 310052 0
Country [1] 310052 0
Other collaborator category [1] 281910 0
Individual
Name [1] 281910 0
Dr James Yun
Address [1] 281910 0
Division of Medicine
Nepean Hospital, Derby St
Kingswood NSW 2747
Country [1] 281910 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308972 0
Northern Sydney Local Health District HREC
Ethics committee address [1] 308972 0
Research Office
Kolling Building, level 13
Reserve Rd
St Leonards
NSW 2065
Ethics committee country [1] 308972 0
Australia
Date submitted for ethics approval [1] 308972 0
31/01/2018
Approval date [1] 308972 0
21/03/2018
Ethics approval number [1] 308972 0
HREC/18/HAWKE/37
Ethics committee name [2] 308995 0
St Vincent's Hospital, Sydney
Ethics committee address [2] 308995 0
Research Office,
St. Vincent’s Health Network
Translational Research Centre
97-105 Boundary Street
Darlinghurst NSW 2010
Ethics committee country [2] 308995 0
Australia
Date submitted for ethics approval [2] 308995 0
12/03/2021
Approval date [2] 308995 0
19/06/2021
Ethics approval number [2] 308995 0
2019/ETH13885

Summary
Brief summary
This is a multi site open label pilot study designed to assess feasibility of further studies looking at the utility of mepolizumab in the treatment of DRESS syndrome. This is an investigator initiated
study, with study drug being provided by GlaxoSmithKline.
DRESS syndrome is a potentially life threatening, idiosyncratic adverse drug reaction. It is typically accompanied by morbilliform rash, fever, lymphadenopathy, haematological abnormalities including eosinophilia and the presence of atypical lymphocytes, and multiple organ involvement. A number of drugs can cause DRESS syndrome and the common causes include antiepileptic
drugs, allopurinol and sulfonamides. We aim to recruit 8 participants over 1.5 - 2 years across the study sites.
Mepolizumab, a humanised monoclonal antibody that targets IL5, will be used in conjunction with standard therapy in participants with DRESS syndrome. Mepolizumab is currently approved for use in refractory eosinophilic asthma.
Participants will be involved in the study for ~6 months. In addition to standard care investigations/monitoring, blood samples for cytokine analysis and lymphocyte profiling, and patient reported outcome measures will be collected at each visit.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112522 0
Prof Andrew Carr
Address 112522 0
Staff Specialist
St Vincent's Public Hospital
C/- IBAC
Xavier Building
390 Victoria St
Darlinghurst
NSW 2010
Country 112522 0
Australia
Phone 112522 0
+61 2 8382 2940
Fax 112522 0
+61 (02) 8382 2090
Email 112522 0
[email protected]
Contact person for public queries
Name 112523 0
Dr James Yun
Address 112523 0
Division of Medicine
Nepean Hospital, Derby St
Kingswood NSW 2747
Country 112523 0
Australia
Phone 112523 0
+61 02 9450 0687
Fax 112523 0
N/A
Email 112523 0
[email protected]
Contact person for scientific queries
Name 112524 0
Dr James Yun
Address 112524 0
Division of Medicine
Nepean Hospital, Derby St
Kingswood NSW 2747
Country 112524 0
Australia
Phone 112524 0
+61 02 9450 0687
Fax 112524 0
N/A
Email 112524 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
In order to protect the privacy of participants, no individual identifiers that would allow the identification of the participant will be used in any report, meeting or publication, or disclosed to a third party.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.