Efficacy of Belimumab and Rituximab Compared to Rituximab Alone for the Treatment of Primary Membranous Nephropathy (ITN080AI)
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 it is currently being tested in other autoimmune diseases, including lupus nephritis and Sjögren's syndrome.
• Subjects must meet all of the following criteria to be eligible for this study-
• Diagnosis of one of the following:
• Primary membranous nephropathy (MN):
• Confirmed by kidney biopsy obtained in the past 5 years, or
• If relapsing following a complete remission or partial remission, confirmed with a kidney biopsy obtained in the past 7 years
• Nephrotic syndrome, and a contraindication to kidney biopsy (e.g., anti-coagulation, solitary kidney, body habitus that increases the risk of biopsy, or other contraindication in the opinion of the investigator).
• Serum anti-PLA2R positive;
• Estimated Glomerular Filtration Rate (eGFR) ≥ 30 mL/min/1.73m^2 while on maximally tolerated renin-angiotensin system (RAS) blockade;
• ≥4 and < 8 g/day that has been present for ≥ 3 months while on while on maximally tolerated RAS blockade, or
• ≥8 g/day while on maximally tolerated RAS blockade.
• Blood pressure while on maximally tolerated RAS blockade:
• Systolic blood pressure ≤ 140 mmHg, and
• Diastolic blood pressure ≤ 90 mmHg