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Trial registered on ANZCTR


Registration number
ACTRN12623001336673
Ethics application status
Approved
Date submitted
16/11/2023
Date registered
19/12/2023
Date last updated
29/05/2024
Date data sharing statement initially provided
19/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing Use of B-cell depletion therapy to Immunoglobulin in Chronic inflammatory demyelinating polyneuropathy (CUBIC) clinical trial.
Scientific title
Comparing Use of B-cell depletion therapy to Immunoglobulin in Chronic inflammatory demyelinating polyneuropathy (CUBIC) clinical trial.
Secondary ID [1] 310945 0
Nil known
Universal Trial Number (UTN)
Trial acronym
CUBIC Clinical Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic inflammatory demyelinating polyneuropathy (CIDP). 332021 0
Condition category
Condition code
Inflammatory and Immune System 328753 328753 0 0
Autoimmune diseases
Neurological 328902 328902 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
It is an inclusion criterion for this trial that participants must have already been receiving intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy (CIDP) for at least 4 months prior to enrolment. Eligible participants will be administered (unblinded) two consecutive doses of RIXIMYO (Rituximab) (1000mg), delivered by intravenous infusion, two weeks apart in Phase 1 of the CUBIC trial. Twelve (12) weeks after dose 1 of RIXIMYO (Rituximab), participants’ Intravenous immunoglobulin dose (participant dependent) will be reduced by 50% and they will have blood samples collected every 3-4 weeks to monitor for B-cell reconstitution. (B-cell reconstitution is participant dependent, however, is estimated between 6-12months after first two doses of RIXIMYO (Rituximab)).

All participants - from the point of B-cell reconstitution - will enter Phase 2 of the CUBIC trial. Participants will have the option of continuing Phase 2 in one of two pathways:
Phase 2A: Administration (unblinded) of two more consecutive doses of RIXIMYO (Rituximab) (1000mg), delivered by intravenous infusion, two weeks apart. Twelve (12) weeks after the 1st round of RIXIMYO (Rituximab), the participants' intravenous immunoglobulin dose will cease and they will have blood samples collected every 3-4 weeks to monitor for B-cell reconstitution. (B-cell reconstitution is participant dependent, however, is estimated between 6-12months after the two doses of RIXIMYO (Rituximab)).
Phase 2B: Continue to receive immunoglobulin infusions at 50% of pre-trial dose and to be clinically monitored for 12 months.

The trial intervention will be delivered in clinic, by the participant's treating neurologist. Adherence to the intervention will be monitored by use of a REDCap instrument, filled out by the treating neurologist and/or study nurse, to document that RIXIMYO (RItuximab) doses were delivered according to protocol.
Intervention code [1] 327375 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 336559 0
The first primary outcome of this trial is to determine the efficacy of B-IT in reducing IVIg requirements in CIDP participants.
Timepoint [1] 336559 0
This assessment will be conducted at baseline, then every 12 weeks (at weeks 3/4, 12, 24, 36 and 48 of Schedule 1, Schedule 2a and Schedule 2b).
Primary outcome [2] 336713 0
The second primary objective of this trial is to determine whether B-IT can safely reduce IVIg requirements in CIDP participants.
Timepoint [2] 336713 0
Assessment will be conducted at baseline and then every 12 weeks (at weeks 12, 24, 36 and 48 of Schedule 1, Schedule 2a and Schedule 2b) by the treating neurologist.
Secondary outcome [1] 428812 0
Utility of serum neurofilament light (sNFL)
Timepoint [1] 428812 0
Blood samples will be collected at baseline, then every 3-4 weeks, depending on immunoglobulin schedule, for the duration of each schedule (up to 48 weeks per schedule).
Secondary outcome [2] 428814 0
COVID-19 immunity
Timepoint [2] 428814 0
Blood samples will be collected from each participant at baseline, then every 3-4 weeks, depending on immunoglobulin schedule, for the duration of each schedule (up to 48 weeks per schedule).
Secondary outcome [3] 428815 0
Covid-19 specific Memory B-cell responses
Timepoint [3] 428815 0
Blood samples will be collected from each participant at baseline, then every 3-4 weeks, depending on immunoglobulin schedule, for the duration of each schedule (up to 48 weeks per schedule).
Secondary outcome [4] 429422 0
Covid-19 specific T-cell responses.
Timepoint [4] 429422 0
Blood samples will be collected from each participant at baseline, then every 3-4 weeks, depending on immunoglobulin schedule, for the duration of each schedule (up to 48 weeks per schedule).
Secondary outcome [5] 429423 0
Covid-19 specific Ig dynamics.
Timepoint [5] 429423 0
Blood samples will be collected from each participant at baseline, then every 3-4 weeks, depending on immunoglobulin schedule, for the duration of each schedule (up to 48 weeks per schedule).
Secondary outcome [6] 429424 0
Cell mediated immunity: B, T, NK, Monocytes/DC
Timepoint [6] 429424 0
Blood samples will be collected from each participant at baseline, then every 3-4 weeks, depending on immunoglobulin schedule, for the duration of each schedule (up to 48 weeks per schedule).
Secondary outcome [7] 429425 0
Cytokines
Timepoint [7] 429425 0
Blood samples will be collected at baseline, then every 3-4 weeks, depending on immunoglobulin schedule, for the duration of each schedule (up to 48 weeks per schedule).
Secondary outcome [8] 429427 0
IRODS MRS grip strength as a CIDP disease measure
Timepoint [8] 429427 0
Assessments will be conducted at baseline and then every 12 weeks (at weeks 12, 24, 36 and 48 of Schedule 1, Schedule 2a and Schedule 2b) by the treating neurologist.
Secondary outcome [9] 429428 0
SF36 as a CIDP disease measure
Timepoint [9] 429428 0
Assessments will be conducted at baseline and then every 12 weeks (at weeks 12, 24, 36 and 48 of Schedule 1, Schedule 2a and Schedule 2b) by the treating neurologist.

Eligibility
Key inclusion criteria
• Adult greater than 18 years with a documented diagnosis of CIDP, according to the European Federation of Neurological Societies/ Peripheral Nerve Society (EFNS/PNS) criteria 2021
• 3 doses of TGA approved COVID-19 vaccinations.
• at least 2 weeks post 3rd dose COVID-19 vaccination.
• greater than 4 months on Ig therapy and planned continuation for at least 9 months.
• No previous history of B-cell depletion therapy.
• Other immunosuppressants acceptable if dose is stable for 6+ months
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Pregnancy or planned pregnancy in the next 12 months
• Has not had 3 doses of TGA approved COVID-19 vaccinations
• Underlying primary immunodeficiency
• Current or planned treatment with plasma exchange
• Intolerance or allergy to RIXIMYO (Rituximab), or its incipient
• Contraindication for RIXIMYO (Rituximab) based on infectious disease screening.
• Diagnosis of diabetes mellitus
• Positive MAG antibodies, paranodal/nodal antibodies

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
Other
Other design features
All participants will be allocated to Schedule 1 upon enrolment. At the point of B-cell reconstitution, participants will continue to Schedule 2 of the trial, and will be given the choice of continuing on Schedule 2a (further Rituximab and no further IVIg), or Schedule 2b (continued 50% IVIg and no further Rituximab).
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/08/2024
Actual
Date of last participant enrolment
Anticipated
30/09/2024
Actual
Date of last data collection
Anticipated
29/12/2028
Actual
Sample size
Target
35
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25831 0
Westmead Hospital - Westmead
Recruitment hospital [2] 25832 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 25833 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 25834 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 41658 0
2145 - Westmead
Recruitment postcode(s) [2] 41659 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 41660 0
2050 - Camperdown
Recruitment postcode(s) [4] 41661 0
2139 - Concord

Funding & Sponsors
Funding source category [1] 315206 0
Government body
Name [1] 315206 0
NHMRC Medical Research Future Fund (MRFF)
Country [1] 315206 0
Australia
Primary sponsor type
Government body
Name
Western Sydney Local Health District
Address
Cnr Hawkesbury & Darcy Rd, Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 317230 0
None
Name [1] 317230 0
Address [1] 317230 0
Country [1] 317230 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314131 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 314131 0
Ethics committee country [1] 314131 0
Australia
Date submitted for ethics approval [1] 314131 0
16/11/2023
Approval date [1] 314131 0
01/04/2024
Ethics approval number [1] 314131 0

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

Contacts
Principal investigator
Name 130522 0
Prof David Brown
Address 130522 0
Westmead Hospital, Cnr Darcy and Hawkesbury Roads, Westmead NSW 2145, Australia
Country 130522 0
Australia
Phone 130522 0
+61 02 8890 6635
Fax 130522 0
(02) 9891 6908
Email 130522 0
david.brown1@health.nsw.gov.au
Contact person for public queries
Name 130523 0
David Brown
Address 130523 0
Westmead Hospital, Cnr Darcy and Hawkesbury Roads, Westmead NSW 2145, Australia
Country 130523 0
Australia
Phone 130523 0
+61 02 8890 6635
Fax 130523 0
(02) 9891 6908
Email 130523 0
david.brown1@health.nsw.gov.au
Contact person for scientific queries
Name 130524 0
David Brown
Address 130524 0
Westmead Hospital, Cnr Darcy and Hawkesbury Roads, Westmead NSW 2145, Australia
Country 130524 0
Australia
Phone 130524 0
+61 02 8890 6635
Fax 130524 0
(02) 9891 6908
Email 130524 0
david.brown1@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Only aggregate participant data will be available from this study.


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.