REmission in Membranous Nephropathy International Trial (REMIT)

NCT06120673 | Withdrawn Phase 3 DMC

• 1 other identifier: AKTN 18.03
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Primary Membranous Nephropathy

Outcome Measures

Primary Outcomes (1)

• 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

  24 months

Secondary Outcomes (15)

• Number of participants in Complete Remission (CR)

  At 6, 12, 18, 24 month

• Number of participants in Partial Remission (PR)

  At 6, 12, 18, 24 month

• Number of participants in CR and/or PR

  At 6, 12, 18, 24 month

• Number of non-serious adverse events of special interest

  Up until 24 months

• Number of serious adverse events

  Up until 24 months

Other Outcomes (11)

• Number of participants in Complete Remission (CR)

  At any point up until end of study (when last participant reaches 24 months - ~42 months)

• Number of participants in Partial Remission (PR)

  At any point up until end of study (when last participant reaches 24 months - ~42 months)

• Number of participants in CR and/or PR

  At any point up until end of study (when last participant reaches 24 months - ~42 months)

Study Arms (2)

Obinutuzumab

EXPERIMENTAL

Drug: Obinutuzumab

Oral prednisolone and cyclophosphamide

ACTIVE COMPARATOR

Drug: Oral prednisolone and cyclophosphamide

Interventions

Obinutuzumab DRUG

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.

Obinutuzumab

Oral prednisolone and cyclophosphamide DRUG

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

Oral prednisolone and cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Able to provide informed consent.
• Primary Membranous Nephropathy (PMN) confirmed by:
• if the clinician decides against a biopsy, the patient must be anti-PLA2R positive and must not have diabetes.
• 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
• Serum albumin \<30 g/L.
• Estimated glomerular filtration rate (eGFR) ≥40 ml/min/1.73m2.
• Treatment with immunosuppression is warranted, as determined by the treating physician.
• Fully vaccinated against COVID-19 according to local practice/recommendation.

You may not qualify if:

• Resistant to rituximab or have had \>2 g of rituximab in the past.
• Resistant to cyclophosphamide or have had a cumulative \>20 g of cyclophosphamide in the past.
• More than 3 years since PMN diagnosis.
• Proteinuria must not have decreased by \>50% over 6 months whilst taking ACE-i/ARB.
• Patients with human immunodeficiency virus (HIV) infection, active hepatitis B or C infection, or other active infections.
• Patients with secondary membranous nephropathy
• Screening for malignancy must be considered especially in cases who are anti-PLA2R negative.
• Patients whose kidney biopsy shows concomitant features of diabetic nephropathy.
• Kidney transplant recipients.
• Pregnancy or breastfeeding.
• Women of childbearing age not willing to use contraception.
• 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.
• Any disorder or condition, in the opinion of the investigator, might pose an unacceptable risk to participant's safety and well-being.
• Inability to understand or comply with the requirements of the study.
• Incapable of recognizing the nature, significance, and scope of the clinical trial or giving consent are excluded, even if they have a legal representative.

Sponsors & Collaborators

• The University of Queensland: lead
• University of Adelaide: collaborator

Study Sites (13)

Canberra Hospital

Garran, Australian Capital Territory, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Location

Bundaberg Hospital

Bundaberg, Queensland, Australia

Location

Cairns Hospital

Cairns, Queensland, Australia

Location

Logan Hospital

Logan City, Queensland, Australia

Location

Mackay Base Hospital

Mackay, Queensland, Australia

Location

Rockhampton Hospital

Rockhampton, Queensland, Australia

Location

Mater Hospital

South Brisbane, Queensland, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Location

MeSH Terms

Interventions

obinutuzumab; Prednisolone; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Chen Au Peh

  The University of Adelaide

  STUDY CHAIR

• Bhadran Bose

  Nepean Blue Mountains Local Health District

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: November 7, 2023
• Study Start: October 31, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028
• Last Updated: November 28, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 2 years after publication of pre-specified analyses
• Access Criteria: 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.

Locations

AU (13)