Actively Recruiting

Phase 2
Age: 18Years - 75Years
All Genders
NCT03949855

Belimumab With Rituximab for Primary Membranous Nephropathy

Led by National Institute of Allergy and Infectious Diseases (NIAID) · Updated on 2026-02-13

58

Participants Needed

20

Research Sites

521 weeks

Total Duration

On this page

Sponsors

N

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

I

Immune Tolerance Network (ITN)

Collaborating Sponsor

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

Belimumab With Rituximab for Primary Membranous Nephropathy

Who Can Participate

Age: 18Years - 75Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 18 to 75 years inclusive
  • Diagnosed primary membranous nephropathy confirmed by kidney biopsy within past 5 years or relapsing primary MN confirmed within past 7 years
  • Nephrotic syndrome with eGFR over 60 mL/min/1.73m2 and no prior immunosuppressant treatment for nephrotic syndrome, or nephrotic syndrome with contraindication to kidney biopsy without secondary cause
  • Positive serum anti-PLA2R antibody test
  • eGFR at least 30 mL/min/1.73m2 on maximally tolerated RAS blockade
  • Proteinuria at least 4 g/day for 3 months or at least 8 g/day while on maximally tolerated RAS blockade
  • Blood pressure controlled with systolic ≤ 140 mmHg and diastolic ≤ 90 mmHg on maximally tolerated RAS blockade
Not Eligible

You will not qualify if you...

  • Secondary causes of membranous nephropathy such as lupus, drug, infection, or malignancy
  • Rituximab use within past 12 months
  • Prior rituximab use over 12 months ago without complete or partial remission or with undetectable CD19 B cells
  • Use of other anti-B cell therapies within past 12 months
  • Cyclophosphamide use within past 3 months
  • Use of other immunosuppressive drugs including cyclosporine, tacrolimus, or corticosteroids within past 30 days
  • Use of investigational biologic or non-biologic agents within specified recent periods
  • Poorly controlled diabetes with HbA1c ≥ 9.0%
  • Diabetic glomerulopathy greater than Class I or with poor diabetic control
  • Unstable kidney function with >20% eGFR decrease in past 3 months
  • Decrease in proteinuria by 50% or more in past 12 months
  • Low white blood cell or neutrophil counts
  • Moderate to severe anemia (hemoglobin < 9 g/dL)
  • History of primary immunodeficiency
  • Low serum IgA
  • Elevated liver enzymes (ALT or AST ≥ 2x upper limit)
  • Positive HIV, untreated hepatitis C, or hepatitis B infection
  • Positive tuberculosis test
  • Significant lung disease or oxygen requirement
  • Recent or active malignancy except certain localized skin or cervical cancers
  • Lack of age-appropriate cancer screening
  • Women pregnant, nursing, or not using approved contraception until week 104
  • Recent or current infections or recent antimicrobial treatment
  • History of severe allergic reactions to study medications
  • Serious suicide risk or recent suicidal behavior
  • Current or recent drug or alcohol abuse
  • Recent vaccination with live vaccine
  • Other conditions or lab abnormalities that increase risk or may affect study results
  • Inability to follow study procedures and visits

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 20 locations

1

University of Alabama at Birmingham School of Medicine: Division of Nephrology

Birmingham, Alabama, United States, 35294

Actively Recruiting

2

University of Arkansas

Little Rock, Arkansas, United States, 72205

Actively Recruiting

3

University of California San Francisco

San Francisco, California, United States, 94146

Actively Recruiting

4

Stanford University School of Medicine: Division of Nephrology

Stanford, California, United States, 94305

Actively Recruiting

5

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center:Division of Nephrology and Hypertension

Torrance, California, United States, 90502

Actively Recruiting

6

University of Colorado

Aurora, Colorado, United States, 80045

Actively Recruiting

7

Mayo Clinic Jacksonville: Department of Nephrology and Hypertension

Jacksonville, Florida, United States, 32224

Actively Recruiting

8

University of Miami Miller School of Medicine, Div of Nephrology

Miami, Florida, United States, 33136

Actively Recruiting

9

Johns Hopkins

Baltimore, Maryland, United States, 21287

Actively Recruiting

10

National Institutes of Health Clinical Center

Bethesda, Maryland, United States, 20892

Actively Recruiting

11

University of Michigan

Ann Arbor, Michigan, United States, 48104

Actively Recruiting

12

University of Minnesota Health Clinical Research Unit

Minneapolis, Minnesota, United States, 55455

Actively Recruiting

13

Washington University in St. Louis

St Louis, Missouri, United States, 63110

Actively Recruiting

14

University of Nebraska

Omaha, Nebraska, United States, 68198

Actively Recruiting

15

Columbia University Medical Center: Division of Nephrology

New York, New York, United States, 10032

Actively Recruiting

16

University of North Carolina School of Medicine: Division of Nephrology and Hypertension, Kidney Center

Chapel Hill, North Carolina, United States, 27599-

Actively Recruiting

17

Cleveland Clinic

Cleveland, Ohio, United States, 44195

Actively Recruiting

18

Ohio State University Wexner Medical Center: Division of Nephrology

Columbus, Ohio, United States, 43210

Actively Recruiting

19

University of Pennsylvania: Department of Medicine: Renal-Electrolyte and Hypertension Division

Philadelphia, Pennsylvania, United States, 19104

Actively Recruiting

20

Providence Medical Research Center, Providence Health Care: Nephrology

Spokane, Washington, United States, 99204

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

DOUBLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

4

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