Belimumab With Rituximab for Primary Membranous Nephropathy
REBOOT
Belimumab and Rituximab Compared to Rituximab Alone for the Treatment of Primary Membranous Nephropathy (ITN080AI)
2 other identifiers
interventional
58
1 country
20
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Mar 2020
Longer than P75 for phase_2
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2019
CompletedFirst Posted
Study publicly available on registry
May 14, 2019
CompletedStudy Start
First participant enrolled
March 6, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2030
February 13, 2026
February 1, 2026
9 years
May 13, 2019
February 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Proportion of Participants in Complete or Partial Remission (CR or PR) at Week 104.
. CR is defined as proteinuria of ≤ 0.3 g/day with a serum albumin ≥ 3.5 g/dL. PR is defined as a 50% or greater decrease in proteinuria compared to baseline and proteinuria \< 3.5 g/day glomerular filtration rate (eGFR) from baseline.
Week 104
Secondary Outcomes (15)
Proportion of Participants in Complete or Partial Remission (CR or PR) at Week 52 and Week 156.
Week 52, Week 156
Proportion of Participants in Complete Remission (CR) at Week 52, Week 104 and Week 156.
Week 52, Week 104, Week 156
Proportion of Participants in PR but not CR at Week 52, Week 104, Week 156.
Week 52, Week 104, Week 156
Time to Relapse for Participants who Achieved CR or PR.
Up to 156 Weeks (3 Years)
Level of Proteinuria at Week 52, Week 104 and Week 156.
Week 52, Week 104, Week 156
- +10 more secondary outcomes
Study Arms (4)
Part A: Low Proteinuria Group - Belimumab and Rituximab
EXPERIMENTALOpen-label pharmacokinetics (PK) phase. Participants with low proteinuria classification will receive belimumab weekly subcutaneous injections (52 doses administered Week 0 to Week 51) and rituximab infusions at Weeks 4 and 6. Low proteinuria classification: The excretion of ≥4 to \<8 g/day of protein by the kidneys in adults. (Normal in adults: 0.15 g/day).
Part A :High Proteinuria Group - Belimumab and Rituximab
EXPERIMENTALOpen-label pharmacokinetics (PK) phase. Participants with high proteinuria classification will receive belimumab weekly subcutaneous injections (52 doses administered Week 0 to Week 51) and rituximab infusions at Weeks 4 and 6. High proteinuria classification: The excretion of ≥8 g/day of protein by the kidneys in adults. (Normal in adults: 0.15 g/day).
Part B: Belimumab and Rituximab
EXPERIMENTALParticipants in the low proteinuria classification stratification, based upon Part A, and randomized to this arm, will receive subcutaneous belimumab 400 mg (two 200 mg injections) once weekly from weeks 0-3, and then 200 mg once weekly from weeks 4-51. Participants will receive rituximab infusions at Weeks 4 and 6. At week 30, participants will be assessed for a response to study treatment. Participants who meet at least two out of the following three criteria at week 30 will be considered to have an inadequate response to study treatment and receive a second course of rituximab (defined as 1000 mg IV given at weeks 34 and 36): * Anti-PLA2R level is ≥ 25% of baseline * Proteinuria is ≥ 50% of baseline * Serum albumin is \< 2.8 g/dL
Part B: Placebo and Rituximab
PLACEBO COMPARATORParticipants in the low proteinuria classification stratification, based upon Part A, and randomized to this arm, will receive subcutaneous belimumab placebo 400 mg (two 200 mg injections) once weekly from weeks 0-3, and then 200 mg once weekly from weeks 4-51. Participants will receive rituximab infusions at Weeks 4 and 6. At week 30, participants will be assessed for a response to study treatment. Participants who meet at least two out of the following three criteria at week 30 will be considered to have an inadequate response to study treatment and receive a second course of rituximab (defined as 1000 mg IV given at weeks 34 and 36): * Anti-PLA2R level is ≥ 25% of baseline * Proteinuria is ≥ 50% of baseline * Serum albumin is \< 2.8 g/dL
Interventions
Belimumab is a recombinant, human, IgG1λ monoclonal antibody. Belimumab will be provided as a 200 mg sterile, liquid product in a prefilled syringe. Each syringe contains 1.0 mL of 200 mg/mL belimumab. Each syringe will be a single use. Standard Weekly dose: Part A: 200 mg. administered subcutaneously. Part B: 400 mg (two 200 mg injections) from weeks 0-3, and then 200 mg from weeks 4-51, administered subcutaneously.
The placebo control will be provided as a sterile liquid product in a prefilled syringe. Each syringe will be of a single use. Standard weekly dose: Part A: 200 mg. administered subcutaneously. Part B: 400 mg (two 200 mg injections) from weeks 0-3, and then 200 mg from weeks 4-51, administered subcutaneously.
Rituximab is a monoclonal antibody with specificity for CD20, a transmembrane protein expressed on B cells from the pre-B to memory cell development stages. Rituximab is supplied at a concentration of 10 mg/mL in either 100 mg/10 mL or 500 mg/50 mL single-use vials for infusion. It is a clear, colorless liquid. Dose: 1000 mg intravenously (IV), Week 4 and -6.
Eligibility Criteria
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
- +24 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)lead
- Immune Tolerance Network (ITN)collaborator
- GlaxoSmithKlinecollaborator
- PPD Development, LPcollaborator
- Rho Federal Systems Division, Inc.collaborator
Study Sites (20)
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
University of Colorado
Aurora, Colorado, 80045, 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
St 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
Related Publications (1)
Ayoub I, Nachman PH. Advances in ANCA-associated vasculitis and lupus nephritis. Nat Rev Nephrol. 2021 Feb;17(2):89-90. doi: 10.1038/s41581-020-00388-x. No abstract available.
PMID: 33311560DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Patrick Nachman
University of Minnesota, Department of Medicine, Division of Renal Diseases and Hypertension
- STUDY CHAIR
Iñaki Sanz
Emory University, Department of Medicine, Division of Rheumatology
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2019
First Posted
May 14, 2019
Study Start
March 6, 2020
Primary Completion (Estimated)
March 1, 2029
Study Completion (Estimated)
March 1, 2030
Last Updated
February 13, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- On average, within 24 months after database lock for the trial.
- Access Criteria
- Open access.
The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.