REMIT is an investigator-initiated, international, multi-centre, prospective, randomised, open-label, parallel-group trial. A total of 224 adult participants with Primary Membranous Nephropathy (PMN) will be recruited from renal units from Australia, New Zealand Canada, Asia, Europe, United Kingdom, and other countries. Participants will be randomised to receive either corticosteroid and cyclophosphamide or obinutuzumab. The primary outcome is a ranked, composite measure based on (a) efficacy, defined as either complete or partial remission of PMN, (b) number of adverse events, and (c) quality of life.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
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.
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
Canberra Hospital
Garran, Australian Capital Territory, Australia
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Sunshine Coast University Hospital
Birtinya, Queensland, Australia
A ranked composite measure based efficacy, safety and quality of life at 24 months
A ranked composite measure comprising of: 1. Efficacy (complete/partial remission) plus safety (type of adverse event) at 24 months 2. Number of adverse events up to 24 months 3. Quality of Life (EQ-5D) averaged over 24 months
Time frame: 24 months
Number of participants in Complete Remission (CR)
Number of participants who have proteinuria of ≤3.0 g/day
Time frame: At 6, 12, 18, 24 month
Number of participants in Partial Remission (PR)
Number of participants who have proteinuria of between \>3.0 and 3.5 g/day and \>50% reduction from baseline proteinuria
Time frame: At 6, 12, 18, 24 month
Number of participants in CR and/or PR
Number of participants who meet complete and/or partial PMN remission definition
Time frame: At 6, 12, 18, 24 month
Number of non-serious adverse events of special interest
Number of protocol defined non-serious events of special interest (related to PMN or the study interventions)
Time frame: Up until 24 months
Number of serious adverse events
Number of protocol defined serious adverse events
Time frame: Up until 24 months
Number of participants with a lack of response to PMN treatment
Number of participants who have \<50% reduction in proteinuria from baseline or worsening (increasing in value from baseline) proteinuria, and had not achieved either PR or CR
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Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia
Bundaberg Hospital
Bundaberg, Queensland, Australia
Cairns Hospital
Cairns, Queensland, Australia
Logan Hospital
Logan City, Queensland, Australia
Mackay Base Hospital
Mackay, Queensland, Australia
Rockhampton Hospital
Rockhampton, Queensland, Australia
Mater Hospital
South Brisbane, Queensland, Australia
...and 3 more locations
Time frame: Up until 24 months
Number of participants who relapse after CR or PR
Number of participant who have a reappearance of proteinuria to \>3.5 g/day at a ≥50% higher level than the lowest post-treatment value in participants who had previously achieved either PR or CR
Time frame: Up until 24 months
Time to first relapse
The time to relapse is the time interval from the last point in time when the participant was in the best remission status (either PR or CR) to the first relapse
Time frame: Up until 24 months
Number of participants who have immunological remission (for anti-PLA2R positive participants)
Number of participants who have their anti-PLA2R-Ab level drop below 2 RU/mL who are ≥14 RU/ml at baseline
Time frame: Up until 24 months
Number of participants who have a requirement for rescue therapy
Number of participants who have a lack of response or relapse at 12 months, and rescue therapies such as obinutuzumab, calcineurin inhibitors, or additional corticosteroid and cyclophosphamide are used.
Time frame: Up until 24 months
Number of participants who exit the trial
Number participant who cease trial follow-up for any reason
Time frame: Up until 24 months
Quality of life scores (EQ-5D-5L)
Quality of life scores using EQ-5D-5L
Time frame: at 3, 6, 9, 12, 15, 18, 24 months
eGRF slope
Change in eGFR slope
Time frame: Up until 24 months
Number of treatment or PMN associated deaths
Number of deaths attributed directly or indirectly to a complication of PMN or the treatment for PMN
Time frame: Up until 24 months
All cause deaths
Number of deaths of any cause
Time frame: Up until 24 months