Belimumab With Rituximab for Primary Membranous Nephropathy

Recruiting now · Phase 2 · Has a placebo group

Conditions studied: Membranous Nephropathy, Nephrotic Syndrome

In brief

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.

Key facts

Study ID

NCT03949855

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

58

Starts

2020-03-06

Expected to finish

2030-03-01

Last updated by the study team

2026-07-21

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subjects must meet all of the following criteria to be eligible for this study-
• Age 18 to 75 years inclusive
• Diagnosis of one of the following:
• Primary MN confirmed by a kidney biopsy within the past 5 years
• 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
• 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
• 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
• Serum anti-PLA2R positive
• eGFR ≥ 30 mL/min/1.73m2 while on maximally tolerated RAS blockade
• Proteinuria:
• ≥ 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,
• ≥ 8 g/day while on maximally tolerated RAS blockade
• Blood pressure while on maximally tolerated RAS blockade:
• Systolic blood pressure ≤ 140 mmHg
• Diastolic blood pressure ≤ 90 mmHg

You may not qualify if…

• Subjects meeting any of the following criteria will not be eligible for this study-
• Secondary cause of MN (e.g., SLE, drug, infection, malignancy) suggested by review of the patient's medical history and/or clinical presentation
• Rituximab use within the previous 12 months
• Rituximab use > 12 months ago:
• With an undetectable CD19 B cell count, or
• 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)
• Use of anti-B cell therapy other than rituximab within the previous 12 months (or 5 half-lives, whichever is greater)
• Cyclophosphamide use within the past 3 months
• Use of other immunosuppressive medications such as cyclosporine or tacrolimus within the past 30 days
• Use of systemic corticosteroids within the past 30 days
• 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
• Use of any non-biologic investigational agent in the past 30 days (or 5 half-lives, whichever is greater)
• Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) ≥ 9.0%
• Patients with diabetic glomerulopathy on renal biopsy that is:
• Greater than Class I diabetic glomerulopathy, or
• Class I diabetic glomerulopathy with a history of poor diabetic control (e.g., HbA1c ≥ 9.0%) since time of biopsy
• 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
• Decrease in proteinuria by 50% or more during the previous 12 months
• WBC count < 3.0 x 103/μl
• Absolute neutrophil count < 1.5 x 103/μl
• Moderately severe anemia (hemoglobin < 9 g/dL)
• History of primary immunodeficiency
• Serum IgA < 10 mg/dL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2x the upper limit of normal (ULN)
• Positive HIV serology

Where it is running

• University of Alabama at Birmingham School of Medicine: Division of Nephrology — Birmingham, Alabama, United States (enrolling)
• University of Arkansas — Little Rock, Arkansas, United States (enrolling)
• University of California San Francisco — San Francisco, California, United States (enrolling)
• Stanford University School of Medicine: Division of Nephrology — Stanford, California, United States (enrolling)
• The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center:Division of Nephrology and Hypertension — Torrance, California, United States (enrolling)
• University of Colorado — Aurora, Colorado, United States (enrolling)
• Mayo Clinic Jacksonville: Department of Nephrology and Hypertension — Jacksonville, Florida, United States (enrolling)
• University of Miami Miller School of Medicine, Div of Nephrology — Miami, Florida, United States (enrolling)
• Johns Hopkins — Baltimore, Maryland, United States (enrolling)
• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (enrolling)
• University of Michigan — Ann Arbor, Michigan, United States (enrolling)
• University of Minnesota Health Clinical Research Unit — Minneapolis, Minnesota, United States (enrolling)
• Washington University in St. Louis — St Louis, Missouri, United States (enrolling)
• University of Nebraska — Omaha, Nebraska, United States (enrolling)
• Columbia University Medical Center: Division of Nephrology — New York, New York, United States (enrolling)
• University of North Carolina School of Medicine: Division of Nephrology and Hypertension, Kidney Center — Chapel Hill, North Carolina, United States (enrolling)
• Cleveland Clinic — Cleveland, Ohio, United States (enrolling)
• Ohio State University Wexner Medical Center: Division of Nephrology — Columbus, Ohio, United States (enrolling)
• University of Pennsylvania: Department of Medicine: Renal-Electrolyte and Hypertension Division — Philadelphia, Pennsylvania, United States (enrolling)
• Providence Medical Research Center, Providence Health Care: Nephrology — Spokane, Washington, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.