MEmbranous Nephropathy Trial Of Rituximab

• Status: Completed
• Trial end date: 2017-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary outcome of this study is to determine whether or not the B cell targeting with Rituximab is non-inferior or more effective than Cyclosporine in inducing long term remission of proteinuria.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Collaborators: Applied Health Research Centre; Case Western Reserve University; CHU de Quebec-Universite Laval; Columbia University; Florida International University; Fulk Family Foundation; Medical College of Wisconsin; NYU Langone Health; Ohio State University; Stanford University; Sunnybrook Health Sciences Centre; The Cleveland Clinic; University Health Network, Toronto; University of Alabama at Birmingham; University of Arizona; University of British Columbia; University of Kansas Medical Center; University of Manchester; University of Michigan; University of Mississippi Medical Center; University of Toronto; University of Washington; Washington University School of Medicine
• Treatments: Cyclosporine; Cyclosporins; Rituximab

Criteria

Inclusion Criteria

• Idiopathic MN with diagnostic biopsy

• Female, must be post-menopausal, surgically sterile or practicing a medically approved method of contraception(no birth-control pill)

• Must be off prednisone or mycophenolate mofetil for >1 month and alkylating agents for >6 months.

• angiotensin-converting-enzyme inhibitor (ACEi) and/or Angiotensin II receptor blockers (ARB), for >3 months prior to randomization and adequate blood pressure (target BP <130/80 millimeter of mercury (mmHg) in >75% of the readings, but subjects with BP <140/80 mmHg in >75% of the readings will be eligible). Patients with documented evidence of >3 months treatment with maximal angiotensin II blockade, on an 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA) reductase inhibitor, and BP control (BP <140/80 mmHg in >75% of the readings) who remain with proteinuria >5g/24h may enter and be randomized to RTX/CSA without the need of the run-in/conservative phase of the study.

• Proteinuria >5g/24h on two 24-hour urine collection collected within 14 days of each other

• Estimated glomerular filtration rate (GFR) ≥40 ml/min/1.73m2 while taking ACEi/ARB therapy OR quantified endogenous creatinine clearance >40 ml/min/1.73m2 based on a 24-hour urine collection.

Exclusion Criteria

• Presence of active infection or a secondary cause of MN (e.g. hepatitis B, systemic lupus erythematosus (SLE), medications, malignancies). Testing for HIV, Hepatitis B and C should have occurred <2 years prior to enrollment into the study.

• Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy. Patients who have recent history of steroid induced diabetes but no evidence on renal biopsy performed within 6 months of entry into the study are eligible for enrollment.

• Pregnancy or breast feeding for safety reasons

• History of resistance to CSA (or other calcineurin inhibitors, e.g. tacrolimus), RTX or alkylating agents (e.g. Cytoxan). Patients who previously responded to CSA/Calcineurin Inhibitor (CNI), RTX or alkylating agents with either a complete remission (CR) or partial remission (PR) but relapsed off CSA/CNI after 3 months or relapsed off RTX or alkylating agent after 6 months are eligible.