Belimumab With Rituximab for Primary Membranous Nephropathy

Inclusion Criteria: Subjects must meet all of the following criteria to be eligible for this study- 1. Age 18 to 75 years inclusive 2. Diagnosis of one of the following: 1. Primary MN confirmed by a kidney biopsy within the past 5 years 2. Primary MN that is relapsing following a CR (Section 3.3.1) or PR (Section 3.3.2), confirmed by a kidney biopsy within the past 7 years 3. Nephrotic syndrome with eGFR \> 60 mL/min/1.73m2 and no history of immunosuppressant treatment (e.g. glucocorticoids, cyclophosphamide, cyclosporine A, tacrolimus, B-cell depleting agent) for nephrotic syndrome, and without evidence of a secondary cause of nephrotic syndrome 4. Nephrotic syndrome and a contraindication to kidney biopsy (e.g., anticoagulation, solitary kidney, body habitus that increases the risk of biopsy, or other contraindication in the opinion of the investigator), and without evidence of a secondary cause of nephrotic syndrome 3. Serum anti-PLA2R positive 4. eGFR ≥ 30 mL/min/1.73m2 while on maximally tolerated RAS blockade 5. Proteinuria: 1. ≥ 4 and \< 8 g/day that has persisted for at least the previous 3 months while on maximally tolerated RAS blockade. Documentation of persistent proteinuria may be from a 24-hour collection or calculated from a spot urine collection. Or, 2. ≥ 8 g/day while on maximally tolerated RAS blockade 6. Blood pressure while on maximally tolerated RAS blockade: 1. Systolic blood pressure ≤ 140 mmHg 2. Diastolic blood pressure ≤ 90 mmHg Exclusion Criteria: Subjects meeting any of the following criteria will not be eligible for this study- 1. Secondary cause of MN (e.g., SLE, drug, infection, malignancy) suggested by review of the patient's medical history and/or clinical presentation 2. Rituximab use within the previous 12 months 3. Rituximab use \> 12 months ago: 1. With an undetectable CD19 B cell count, or 2. Did not result in a CR (Section 3.3.1) or PR (Section 3.3.2) with rituximab treatment alone (e.g., without other immunosuppressive or immunomodulatory therapy) 4. Use of anti-B cell therapy other than rituximab within the previous 12 months (or 5 half-lives, whichever is greater) 5. Cyclophosphamide use within the past 3 months 6. Use of other immunosuppressive medications such as cyclosporine or tacrolimus within the past 30 days 7. Use of systemic corticosteroids within the past 30 days 8. Use of any biologic investigational agent (defined as any drug not approved for sale in the country it is used) in the previous 12 months 9. Use of any non-biologic investigational agent in the past 30 days (or 5 half-lives, whichever is greater) 10. Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) ≥ 9.0% 11. Patients with diabetic glomerulopathy on renal biopsy that is: 1. Greater than Class I diabetic glomerulopathy, or 2. Class I diabetic glomerulopathy with a history of poor diabetic control (e.g., HbA1c ≥ 9.0%) since time of biopsy 12. Unstable kidney function defined as \> 20% decrease in eGFR during the previous 3 months due to primary MN, as determined by the site investigator in consultation with the protocol chair 13. Decrease in proteinuria by 50% or more during the previous 12 months 14. WBC count \< 3.0 x 103/μl 15. Absolute neutrophil count \< 1.5 x 103/μl 16. Moderately severe anemia (hemoglobin \< 9 g/dL) 17. History of primary immunodeficiency 18. Serum IgA \< 10 mg/dL 19. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2x the upper limit of normal (ULN) 20. Positive HIV serology 21. Positive HCV serology, unless treated with anti-viral therapy with achievement of a sustained virologic response (undetectable viral load 24 weeks after cessation of therapy) 22. Evidence of current or prior infection with hepatitis B, as indicated by positive HBsAg or positive HBcAb 23. Positive QuantiFERON - TB Gold test results. PPD tuberculin test may be substituted for QuantiFERON - TB Gold test 24. History of lung disease with FVC \< 70% predicted, DLCO \< 70% predicted, or requiring supplemental oxygen 25. History of malignant neoplasm within the last 5 years except for basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years 26. Absence of individualized, age-appropriate cancer screening 27. Women of child-bearing potential who are pregnant, nursing, or unwilling to be sexually inactive or use FDA-approved contraception until week 104 28. Acute or chronic infection, including current use of suppressive therapy for chronic infection, hospitalization for treatment of infection in the past 60 days, or parenteral anti-microbial (including anti-bacterial, anti-viral, or anti-fungal agents) use in the past 60 days for infection 29. History of an anaphylactic reaction or known sensitivity or intolerance to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies, including rituximab or belimumab 30. Evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months, or who in the investigator's judgment, poses a significant suicide risk 31. Evidence of current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence in the past 12 months 32. Vaccination with a live vaccine within the past 30 days 33. Other diseases or conditions or other clinically significant abnormal laboratory value which in the opinion of the investigator would put the patient at risk or confound the results of the study 34. Inability to comply with study and follow-up procedures