NCT03949855 Belimumab With Rituximab for Primary Membranous Nephropathy

Eligibility & Interventions

Eligibility Fast-Check

Enter your details for a quick preliminary check. This does not replace medical advice.

What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.

This trial targets 58 participants in total. It began in 2020-03-06 with a primary completion date of 2029-03-01.

Brief Summary

The primary objective of this study is to evaluate the effectiveness of belimumab and intravenous rituximab co-administration at inducing a complete or partial remission (CR or PR) compared to rituximab alone in participants with primary membranous nephropathy. Background: Primary membranous nephropathy (MN) is among the most common causes of nephrotic syndrome in adults. MN affects individuals of all ages and races. The peak incidence of MN is in the fifth decade of life. Primary MN is recognized to be an autoimmune disease, a disease where the body's own immune system causes damage to kidneys. This damage can cause the loss of too much protein in the urine. Drugs used to treat MN aim to reduce the attack by one's own immune system on the kidneys by blocking inflammation and reducing the immune system's function. These drugs can have serious side effects and often do not cure the disease. There is a need for new treatments for MN that are better at improving the disease while reducing fewer treatment associated side effects. In this study, researchers will evaluate if treatment with a combination of two different drugs, belimumab and rituximab, is effective at blocking the immune attacks on the kidney compared to rituximab alone. Rituximab works by decreasing a type of immune cell, called B cells. B cells are known to have a role in MN. Once these cells are removed, disease may become less active or even inactive. However, after stopping treatment, the body will make new B cells which may cause disease to become active again. Belimumab works by decreasing the new B cells produced by the body and, may even change the type of new B cells subsequently produced. Belimumab is approved by the US Food and Drug Administration (FDA) to treat systemic lupus erythematosus (also referred to as lupus or SLE). Rituximab is approved by the FDA to treat some types of cancer, rheumatoid arthritis, and vasculitis. Neither rituximab nor belimumab is approved by the FDA to treat MN. Treatment with a combination of belimumab and rituximab has not been studied in individuals with MN, but has been tested in other autoimmune diseases, including lupus nephritis and Sjögren's syndrome.

Eligibility Criteria

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

Contact & Investigator

Frequently Asked Questions

Related Trials