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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06120673




Registration number
NCT06120673
Ethics application status
Date submitted
12/12/2022
Date registered
7/11/2023

Titles & IDs
Public title
REmission in Membranous Nephropathy International Trial (REMIT)
Scientific title
International, Multi-centre Randomised Clinical Trial of Obinutuzumab Versus Corticosteroid and Cyclophosphamide in Primary Membranous Nephropathy (REMIT Trial).
Secondary ID [1] 0 0
AKTN 18.03
Universal Trial Number (UTN)
Trial acronym
REMIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Membranous Nephropathy 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Oral prednisolone and cyclophosphamide

Experimental: Obinutuzumab -

Active comparator: Oral prednisolone and cyclophosphamide -


Treatment: Drugs: Obinutuzumab
Participants will receive an intravenous infusion of 1,000mg Obinutuzumab at Weeks 0, 2, 24 and 26.

Prior to the administration of obinutuzumab, the participant will receive pre-medications consisting of all three:

* IV methylprednisolone 80 mg,
* Paracetamol 1,000 mg orally,
* Either cetirizine 10 mg orally or diphenhydramine 50 mg orally. These pre-medications must be completed between 30 to 60 minutes prior to the obinutuzumab infusion.

Treatment: Drugs: Oral prednisolone and cyclophosphamide
Participants will receive a combination of oral prednisolone and cyclophosphamide with 2 options (Option A and B).

Option A: Cyclical prednisolone and cyclophosphamide with IV methylprednisolone

* IV methylprednisolone 500-1000 mg will be given on days 1, 2 and 3 at the start of months 1, 3, and 5.
* Oral prednisolone will be given at 0.5 mg/kg/day (max 50 mg/day) in months 1, 3, and 5.
* Oral cyclophosphamide will be given in months 2, 4 and 6, adjusted by age and weight

Option B: Concurrent prednisolone and cyclophosphamide without IV methylprednisolone

* Oral prednisolone will be given to meet a cumulative dose equivalent to 0.5 mg/kg/day for 90 days (max 50 mg/day).
* Oral cyclophosphamide will be given for 90 days, adjusted by age and weight
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
A ranked composite measure based efficacy, safety and quality of life at 24 months
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
Number of participants in Complete Remission (CR)
Timepoint [1] 0 0
At 6, 12, 18, 24 month
Secondary outcome [2] 0 0
Number of participants in Partial Remission (PR)
Timepoint [2] 0 0
At 6, 12, 18, 24 month
Secondary outcome [3] 0 0
Number of participants in CR and/or PR
Timepoint [3] 0 0
At 6, 12, 18, 24 month
Secondary outcome [4] 0 0
Number of non-serious adverse events of special interest
Timepoint [4] 0 0
Up until 24 months
Secondary outcome [5] 0 0
Number of serious adverse events
Timepoint [5] 0 0
Up until 24 months
Secondary outcome [6] 0 0
Number of participants with a lack of response to PMN treatment
Timepoint [6] 0 0
Up until 24 months
Secondary outcome [7] 0 0
Number of participants who relapse after CR or PR
Timepoint [7] 0 0
Up until 24 months
Secondary outcome [8] 0 0
Time to first relapse
Timepoint [8] 0 0
Up until 24 months
Secondary outcome [9] 0 0
Number of participants who have immunological remission (for anti-PLA2R positive participants)
Timepoint [9] 0 0
Up until 24 months
Secondary outcome [10] 0 0
Number of participants who have a requirement for rescue therapy
Timepoint [10] 0 0
Up until 24 months
Secondary outcome [11] 0 0
Number of participants who exit the trial
Timepoint [11] 0 0
Up until 24 months
Secondary outcome [12] 0 0
Quality of life scores (EQ-5D-5L)
Timepoint [12] 0 0
at 3, 6, 9, 12, 15, 18, 24 months
Secondary outcome [13] 0 0
eGRF slope
Timepoint [13] 0 0
Up until 24 months
Secondary outcome [14] 0 0
Number of treatment or PMN associated deaths
Timepoint [14] 0 0
Up until 24 months
Secondary outcome [15] 0 0
All cause deaths
Timepoint [15] 0 0
Up until 24 months

Eligibility
Key inclusion criteria
1. Age =18 years.
2. Able to provide informed consent.
3. Primary Membranous Nephropathy (PMN) confirmed by:

1. Kidney biopsy (anti-PLA2R negative patients are eligible for inclusion if PMN is confirmed on biopsy. Kidney biopsy is generally encouraged to confirm diagnosis of PMN) or
2. if the clinician decides against a biopsy, the patient must be anti-PLA2R positive and must not have diabetes.
4. Proteinuria =4 g/24h despite supportive treatment for at least 6 months with maximally tolerated dose of ACE-i or ARB (dose to be stable for at least 4 weeks), confirmed at final screening before randomisation
5. Serum albumin <30 g/L.
6. Estimated glomerular filtration rate (eGFR) =40 ml/min/1.73m2.
7. Treatment with immunosuppression is warranted, as determined by the treating physician.
8. Fully vaccinated against COVID-19 according to local practice/recommendation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Resistant to rituximab or have had >2 g of rituximab in the past.
2. Resistant to cyclophosphamide or have had a cumulative >20 g of cyclophosphamide in the past.
3. More than 3 years since PMN diagnosis.
4. Proteinuria must not have decreased by >50% over 6 months whilst taking ACE-i/ARB.
5. Patients with human immunodeficiency virus (HIV) infection, active hepatitis B or C infection, or other active infections.
6. Patients with secondary membranous nephropathy
7. Screening for malignancy must be considered especially in cases who are anti-PLA2R negative.
8. Patients whose kidney biopsy shows concomitant features of diabetic nephropathy.
9. Kidney transplant recipients.
10. Pregnancy or breastfeeding.
11. Women of childbearing age not willing to use contraception.
12. Suspected or known hypersensitivity, allergy, and/or immunogenic reaction history to monoclonal antibodies, corticosteroid, cyclophosphamide, any of their ingredients, and any other drugs from these same pharmacotherapeutic groups.
13. Any disorder or condition, in the opinion of the investigator, might pose an unacceptable risk to participant's safety and well-being.
14. Inability to understand or comply with the requirements of the study.
15. Incapable of recognizing the nature, significance, and scope of the clinical trial or giving consent are excluded, even if they have a legal representative.
16. Use of an investigational agent <30 days or within five half-lives of the investigational agents (whichever is longer), whose effect or toxicity may overlap with that of obinutuzumab, prednisolone, cyclophosphamide, or their metabolites.
17. Active Tuberculosis infection. Testing for latent disease may be performed at screening if required by local regulations or in accordance with local clinical practice. Latent disease after completion of appropriate treatment is not exclusionary.
18. Low peripheral B-cell count (as per local reference range) . B-cell count must be checked, particularly in those who have received rituximab, cyclophosphamide or both anytime in the past.
19. Use of SGLT2-i and GLP-1 agonist within 90 days prior to randomisation.

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)
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
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
31/07/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2028
Actual
Sample size
Target
224
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,TAS,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [5] 0 0
Bundaberg Hospital - Bundaberg
Recruitment hospital [6] 0 0
Cairns Hospital - Cairns
Recruitment hospital [7] 0 0
Logan Hospital - Logan
Recruitment hospital [8] 0 0
Mackay Base Hospital - Mackay
Recruitment hospital [9] 0 0
Rockhampton Hospital - Rockhampton
Recruitment hospital [10] 0 0
Mater Hospital - South Brisbane
Recruitment hospital [11] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [12] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [13] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
- Garran
Recruitment postcode(s) [2] 0 0
- Camperdown
Recruitment postcode(s) [3] 0 0
- Birtinya
Recruitment postcode(s) [4] 0 0
- Brisbane
Recruitment postcode(s) [5] 0 0
- Bundaberg
Recruitment postcode(s) [6] 0 0
- Cairns
Recruitment postcode(s) [7] 0 0
- Logan
Recruitment postcode(s) [8] 0 0
- Mackay
Recruitment postcode(s) [9] 0 0
- Rockhampton
Recruitment postcode(s) [10] 0 0
- South Brisbane
Recruitment postcode(s) [11] 0 0
- Woolloongabba
Recruitment postcode(s) [12] 0 0
- Hobart
Recruitment postcode(s) [13] 0 0
- Murdoch

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of Adelaide
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Chen Au Peh
Address 0 0
The University of Adelaide
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Peta-Anne Paul-Brent
Address 0 0
Country 0 0
Phone 0 0
+61411 397 776
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Data sets will be made available to researchers within the REMIT Study for analysis of sub-studies and country specific outcomes after the primary manuscript has been accepted for publication.

For researchers outside the REMIT study, individual participant data will be made available upon request to a Data Access Committee, a review board set up to assess proposals based on sound science, benefit-risk balancing and research team expertise.

Where data linkage has been used to estimate health care services utilisation, data sharing will be determined by the specific requirements of the data custodians. In some circumstances it may not be possible to share participant level data beyond the country in which it was collected. This will be addressed on a jurisdiction basis.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
2 years after publication of pre-specified analyses
Available to whom?
Data sets will be made available to researchers within the REMIT Study for analysis of sub-studies and country specific outcomes after the primary manuscript has been accepted for publication.

For researchers outside the REMIT study, individual participant data will be made available upon request to a Data Access Committee, a review board set up to assess proposals based on sound science, benefit-risk balancing and research team expertise.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06120673