RECRUITING

Belimumab With Rituximab for Primary Membranous Nephropathy

Conditions

Membranous Nephropathy Nephrotic Syndrome Primary Membranous Nephropathy Pharmacokinetics (PK) Analysis Double-Blind (Masked), Placebo-Controlled Clinical Trial Co-administered belimumab and rituximab

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2020-03-06

Study Completion:2030-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03949855

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
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	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

Inclusion Criteria

Exclusion Criteria

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

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

Contacts and Locations

Principal Investigator

Patrick Nachman, M.D.

STUDY_CHAIR

University of Minnesota, Department of Medicine, Division of Renal Diseases and Hypertension

Iñaki Sanz, M.D.

STUDY_CHAIR

Emory University, Department of Medicine, Division of Rheumatology

Study Locations (Sites)

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

Birmingham, Alabama, 35294

United States

University of Arkansas

Little Rock, Arkansas, 72205

United States

University of California San Francisco

San Francisco, California, 94146

United States

Stanford University School of Medicine: Division of Nephrology

Stanford, California, 94305

United States

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

Torrance, California, 90502

United States

Mayo Clinic Jacksonville: Department of Nephrology and Hypertension

Jacksonville, Florida, 32224

United States

University of Miami Miller School of Medicine, Div of Nephrology

Miami, Florida, 33136

United States

Johns Hopkins

Baltimore, Maryland, 21287

United States

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

University of Michigan

Ann Arbor, Michigan, 48104

United States

University of Minnesota Health Clinical Research Unit

Minneapolis, Minnesota, 55455

United States

Washington University in St. Louis

Saint Louis, Missouri, 63110

United States

University of Nebraska

Omaha, Nebraska, 68198

United States

Columbia University Medical Center: Division of Nephrology

New York, New York, 10032

United States

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

Chapel Hill, North Carolina, 27599-

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

Ohio State University Wexner Medical Center: Division of Nephrology

Columbus, Ohio, 43210

United States

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

Philadelphia, Pennsylvania, 19104

United States

Providence Medical Research Center, Providence Health Care: Nephrology

Spokane, Washington, 99204

United States

Collaborators and Investigators

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Patrick Nachman, M.D., STUDY_CHAIR, University of Minnesota, Department of Medicine, Division of Renal Diseases and Hypertension
Iñaki Sanz, M.D., STUDY_CHAIR, Emory University, Department of Medicine, Division of Rheumatology

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-03-06

Study Completion Date2030-03-01

Study Record Updates

Study Start Date2020-03-06

Study Completion Date2030-03-01

Terms related to this study

Keywords Provided by Researchers

Primary Membranous Nephropathy
nephrotic syndrome
Pharmacokinetics (PK) Analysis
Double-Blind (Masked), Placebo-Controlled Clinical Trial
Co-administered belimumab and rituximab

Additional Relevant MeSH Terms

Membranous Nephropathy
Nephrotic Syndrome