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Trial registered on ANZCTR


Registration number
ACTRN12621001502820
Ethics application status
Approved
Date submitted
27/09/2021
Date registered
4/11/2021
Date last updated
13/04/2024
Date data sharing statement initially provided
4/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Reducing the frequency of Autoimmune adverse events in the treatment of Multiple sclerosis with alemtuzumab using B-celL dEpletion (RAMBLE): a phase II, randomised, placebo-controlled clinical trial.
Scientific title
Reducing the frequency of Autoimmune adverse events in the treatment of Multiple sclerosis with alemtuzumab using B-celL dEpletion (RAMBLE): a phase II, randomised, placebo-controlled clinical trial.
Secondary ID [1] 305412 0
nil
Universal Trial Number (UTN)
N/A
Trial acronym
RAMBLE
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 323783 0
Condition category
Condition code
Neurological 321295 321295 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The investigational product is rituximab, which is a monoclonal antibody against CD20 that cause lysis of B-lymphocytes. The antibody is a humanised mouse antibody and is administered intravenously via an infusion over 30 minutes. The dosage to be used is 100 mg/m2 of estimated body surface area (BSA). BSA will be estimated based on height and weight according to the Du Bois formula.

Arm 1: Intervention
Arm 2: Placebo
Intervention code [1] 321819 0
Treatment: Drugs
Comparator / control treatment
Placebo will be 0.9% sodium chloride, which as a colourless solution is indistinguishable from diluted rituximab
Control group
Placebo

Outcomes
Primary outcome [1] 329074 0
Frequency of autoimmune adverse events (time to event)

Assessed via Monitoring visits , MRI scans, blood tests, liver function tests and urine tests

Timepoint [1] 329074 0
Time point: at 3 years post trial commencement (31/12/2024)

Monitoring Visits (every 6 months) intercurrent illness, relapse history and concomitant medications, EDSS change, MSIS-29 change

MRI every 12 months - Looking for Number of new T2 MRI brain lesions, Number of new Gd-enhancing lesions

FBC/lymphocyte subsets – lymphocyte subsets will be performed at weeks -1, 4, 9, 13, 26, 35, 50, 57, 61, 65, 78, 83 and 104. - B cell subpopulation counts at theses times
Secondary outcome [1] 402184 0
To assess the safety and efficacy (MS disease activity related) of this therapeutic approach.
To assess the profile of the immune repertoire of T and B-cells that re-emerge with this therapeutic approach. Assessed via Monitoring visits , MRI scans, blood tests, liver function tests and urine tests
Timepoint [1] 402184 0
Time point: at 3 years post trial commencement (31/12/2024)

Monitoring Visits (every 6 months) intercurrent illness, relapse history and concomitant medications, EDSS change, MSIS-29 change

MRI every 12 months - Looking for Number of new T2 MRI brain lesions, Number of new Gd-enhancing lesions

FBC/lymphocyte subsets – lymphocyte subsets will be performed at weeks -1, 4, 9, 13, 26, 35, 50, 57, 61, 65, 78, 83 and 104. - B cell subpopulation counts at theses times

Eligibility
Key inclusion criteria
- Diagnosed with relapsing remitting MS (RRMS) by a neurologist
- Diagnosis of MS meeting 2017 McDonald criteria
- Diagnosed with MS within the previous 10 years
-Expanded disability status scale (EDSS)15 score < 5.0
-English speaking or non-English speaking who can ensure external interpreter assistance (e.g. relative or friend) to attend all visits for the duration of the clinical trial.
-Available to attend clinic visits
-Willing to sign up for and comply with Bloodwatch monitoring program
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Known or suspected prior autoimmune disease (other than MS)
-Any other serious co-morbidity that in the view of the investigator would preclude participation in the study
- Pregnant (if female)
- Currently lactating (if female)
-Unwilling or unable to use appropriate contraception for the treatment phase of the study (2 years) – male or female
-Recent or current history of major depression, bipolar disorder, psychosis or suicidality
-Currently or recently taking any illicit substances (including any cannabis product)
-Allergy to valaciclovir
-Allergy to Bactrim, Trimethoprim or Sulphur based antibiotics

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
At the screening visit, participants will be assigned a unique participant Screening Number. At the baseline/enrolment visit, after eligibility is confirmed and the full consent form has been signed, a Participant Identification Number (PIDN) will be assigned. PIDNs will be randomly assigned to intervention or placebo groups according to the randomisation code provided to the pharmacy. Randomisation codes will only be visible to site pharmacists who will make up the active treatment and placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised at enrolment to treatment with rituximab or placebo at a 2:1 ratio. Randomisation will be performed using the ranomisation module of the REDCap database based on a random number sequence produced in Excel®, Microsoft (Seattle, CA, USA) stratified by site, sex and age. This randomization sheet will be generated by Assoc/Prof Jing Sun. There will a cap of 20 participants for any single site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The two groups will be compared using a Cox Proportional Hazards time to event analysis (with onset of autoimmune adverse event as the event of interest). An intention to treat method incorporating any potential confounders identified as having a significant impact on this outcome to confirm any findings are not due to random or stratified bias in baseline parameters will be used. Other adverse events will be compared using frequencies and chi-squared statistics where relevant. Efficacy in terms of MS outcomes will be analysed using time to event analysis (Cox Proportional Hazards method) for annualized relapse rate and sustained disability progression (6 months). Other secondary outcomes (e.g. change in EDSS, new T2 and Gd-enhancing MR imaging lesions) will be assessed using appropriate non-parametric statistics. Any effect of laboratory measures (lymphocyte subsets, vitamin D levels) and baseline characteristics will be explored using appropriate single and multivariable statistics. All statistical analyses will be conducted using STATA® v16 software .

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/01/2022
Actual
3/05/2022
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
80
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 20607 0
Gold Coast University Hospital - Southport
Recruitment hospital [2] 20608 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 20609 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [4] 20610 0
Townsville University Hospital - Douglas
Recruitment hospital [5] 20611 0
Mater Private Hospital - South Brisbane
Recruitment hospital [6] 20612 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 35398 0
4215 - Southport
Recruitment postcode(s) [2] 35399 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 35400 0
4575 - Birtinya
Recruitment postcode(s) [4] 35401 0
4814 - Douglas
Recruitment postcode(s) [5] 35402 0
4101 - South Brisbane
Recruitment postcode(s) [6] 35403 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 309776 0
Charities/Societies/Foundations
Name [1] 309776 0
Brazil Family Foundation
Country [1] 309776 0
Australia
Primary sponsor type
University
Name
Griffith University
Address
1 Parklands Dr
Gold Cost Campus
Griffith University QLD 4111
Australia
Country
Australia
Secondary sponsor category [1] 310807 0
None
Name [1] 310807 0
Address [1] 310807 0
Country [1] 310807 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309528 0
Griffth University Human Research Ethics Committee
Ethics committee address [1] 309528 0
Ethics committee country [1] 309528 0
Australia
Date submitted for ethics approval [1] 309528 0
27/09/2021
Approval date [1] 309528 0
31/01/2022
Ethics approval number [1] 309528 0
HREC/2021/QGC/75077

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114294 0
Prof Simon Broadley
Address 114294 0
School of Medicine and Dentistry
Gold Coast Campus
Griffith University QLD 4222
Country 114294 0
Australia
Phone 114294 0
+61 07 5678 0174
Fax 114294 0
Email 114294 0
[email protected]
Contact person for public queries
Name 114295 0
Simon Broadley
Address 114295 0
School of Medicine and Dentistry
Gold Coast Campus
Griffith University QLD 4222
Country 114295 0
Australia
Phone 114295 0
+61 07 5678 0174
Fax 114295 0
Email 114295 0
[email protected]
Contact person for scientific queries
Name 114296 0
Simon Broadley
Address 114296 0
School of Medicine and Dentistry
Gold Coast Campus
Griffith University QLD 4222
Country 114296 0
Australia
Phone 114296 0
+61 07 5678 0174
Fax 114296 0
Email 114296 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data can be made available on request to the principal investigator and subject to approval by the Griffith University Human Research Ethics Committee.
When will data be available (start and end dates)?
After completion of the study (31/12/2026) and for a period of 15 years thereafter.
Available to whom?
Appropriately qualified researchers as judged by the principal investigator and Griffith University Human Research Ethics Committee
Available for what types of analyses?
Appropriate secondary analyses
How or where can data be obtained?
By direct approach to the principal investigator

Simon Broadley
Professor of Neurology
School of Medicine
Gold Coast Campus
Griffith University QLD 4222
AUSTRALIA
Tel: +61 7 5678 0174
Fax: +61 7 5678 0303
[email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
13377Study protocol    382809-(Uploaded-21-02-2024-17-42-33)-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
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