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Combining belimumab and rituximab for treating primary membranous nephropathy

Belimumab and Rituximab Compared to Rituximab Alone for the Treatment of Primary Membranous Nephropathy (ITN080AI)

PHASE2 · National Institute of Allergy and Infectious Diseases (NIAID) · NCT03949855

This study is testing if combining two medications, belimumab and rituximab, can help adults with primary membranous nephropathy feel better and achieve remission more effectively than using rituximab alone.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment58 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorNational Institute of Allergy and Infectious Diseases (NIAID) (nih)
Drugs / interventionsRituximab, belimumab, cyclophosphamide
Locations20 sites (Birmingham, Alabama and 19 other locations)
Trial IDNCT03949855 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of co-administering belimumab and rituximab in inducing remission in adults with primary membranous nephropathy. The study is divided into two parts: an open-label pharmacokinetics analysis comparing belimumab exposure in participants with low and high proteinuria, followed by a potential dose adjustment based on the findings. Participants will receive belimumab weekly and rituximab intravenously at specified intervals, with follow-up extending to 156 weeks post-treatment. The goal is to determine if this combination therapy can improve treatment outcomes compared to rituximab alone.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 75 with a confirmed diagnosis of primary membranous nephropathy or nephrotic syndrome without prior immunosuppressant treatment.

Not a fit: Patients with secondary causes of nephrotic syndrome or those who have previously received immunosuppressive treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for patients suffering from primary membranous nephropathy.

How similar studies have performed: While the combination of belimumab and rituximab is a novel approach, similar studies have shown promise in treating autoimmune conditions, suggesting potential for success.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Birmingham, Alabama and 19 other locations

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Membranous Nephropathy, Nephrotic Syndrome, Primary Membranous Nephropathy, nephrotic syndrome, Pharmacokinetics Analysis, Double-Blind, Placebo-Controlled Clinical Trial, Co-administered belimumab and rituximab

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.