REmission in Membranous Nephropathy International Trial (REMIT)

• Status: Not yet recruiting
• Trial end date: 2028-01-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The University of Queensland
• Collaborator: University of Adelaide
• Treatments: Cyclophosphamide; Obinutuzumab; Prednisolone

Criteria

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.

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.