Belimumab With Rituximab for Primary Membranous Nephropathy

• Status: Recruiting
• Trial end date: 2026-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to evaluate the effectiveness of belimumab and intravenous rituximab co-administration at inducing a complete remission (CR) compared to rituximab alone in participants with PM.

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.

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

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: GlaxoSmithKline; Immune Tolerance Network (ITN); PPD; Rho Federal Systems Division, Inc.
• Treatments: Belimumab; Rituximab

Criteria

Inclusion Criteria:

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;

• Proteinuria:

• ≥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

Exclusion Criteria:

Subjects meeting any of the following criteria will not be eligible for this study-

• Secondary cause of membranous nephropathy (MN) (e.g., systemic lupus erythematosus (SLE), drug, infection, malignancy) suggested by review of the subject'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 complete remission (CR) or partial remission (PR) 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, which ever 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 > 15% decrease in the Estimated Glomerular Filtration Rate (eGFR) during the previous 3 months;

• Decrease in proteinuria by 50% or more during the previous 12 months;

• White blood cell (WBC) count < 3.0 x 10^3/µl;

• Absolute neutrophil count < 1.5 x 10^3/µl;

• Moderately severe anemia (hemoglobin <9mg/dL);

• History of primary immunodeficiency;

• Serum immunoglobulin A (IgA) < 10 mg/dL;

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = ≥2 times the upper limit of normal (ULN);

• Positive human immunodeficiency virus (HIV) serology;

• Positive hepatitis C virus (HCV) serology, unless treated with anti-viral therapy with achievement of a sustained virologic response (undetectable viral load 24 weeks after cessation of therapy);

• Evidence of current or prior infection with hepatitis B, as indicated by a positive HBsAg, positive HBcAb, or positive HBsAb serology without history of vaccination;

• Positive QuantiFERON - tuberculosis (TB) Gold test results,

--Note: Tuberculin Purified Protein Derivative (PPD) test may be substituted for QuantiFERON - TB Gold test.

• History of lung disease with FVC < 70% predicted, DLCO < 70% predicted, or requiring supplemental oxygen;

• History of malignant neoplasm within the last 5 years,

--Exception: 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.

• Absence of individualized, age-appropriate cancer screening;

• Women of child-bearing potential who are pregnant, nursing, or unwilling to be sexually inactive or use FDA-approved contraception until study week 104;

• 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.

• History of anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies, including:

• rituximab, or

• belimumab.

• Evidence of serious suicide risk, including:

• any history of suicidal behavior in the last 6 months,

• any suicidal ideation in the last 2 months, or

• who, in the investigator's judgment, pose a significant suicide risk.

• Evidence of current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence in the past 12 months;

• Vaccination with a live vaccine within the past 30 days;

• Other diseases or conditions which, in the opinion of the investigator, would put the subject at risk or confound the results of the study; or

• Inability to comply with study and follow-up procedures.