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

Who is this study for? Patients with primary membranous nephropathy
What treatments are being studied? Belimumab+Rituximab
Status: Recruiting
Location: See all (17) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 75
Healthy Volunteers: No
View:

• 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

Locations
United States
Alabama
University of Alabama at Birmingham School of Medicine: Division of Nephrology
Recruiting
Birmingham
California
Stanford University School of Medicine: Division of Nephrology
Recruiting
Stanford
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center:Division of Nephrology and Hypertension
Recruiting
Torrance
Florida
Mayo Clinic Jacksonville: Department of Nephrology and Hypertension
Recruiting
Jacksonville
Massachusetts
Boston Medical Center: Renal Medicine
Not yet recruiting
Boston
Maryland
National Institutes of Health Clinical Center
Recruiting
Bethesda
Minnesota
University of Minnesota Health Clinical Research Unit
Recruiting
Minneapolis
Mayo Clinic Rochester: Department of Nephrology and Hypertension
Not yet recruiting
Rochester
North Carolina
University of North Carolina School of Medicine: Division of Nephrology and Hypertension, Kidney Center
Recruiting
Chapel Hill
New York
Columbia University Medical Center: Division of Nephrology
Recruiting
New York
Ohio
Ohio State University Wexner Medical Center: Division of Nephrology
Recruiting
Columbus
Pennsylvania
University of Pennsylvania: Department of Medicine: Renal-Electrolyte and Hypertension Division
Recruiting
Philadelphia
Tennessee
Vanderbilt University Medical Center: Division of Nephrology and Hypertension
Recruiting
Nashville
Washington
Providence Medical Research Center, Providence Health Care: Nephrology
Recruiting
Spokane
Other Locations
Canada
University of Toronto, Sunnybrook Health Sciences Centre: Nephrology
Not yet recruiting
Toronto
University of Toronto, University Health Network: Nephrology
Not yet recruiting
Toronto
The University of British Columbia: Division of Nephrology
Not yet recruiting
Vancouver
Time Frame
Start Date: December 18, 2019
Estimated Completion Date: October 2026
Participants
Target number of participants: 124
Treatments
Experimental: Part A: Low Proteinuria Group - Belimumab and Rituximab
Open-label pharmacokinetics (PK) phase.~Ten 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).
Experimental: Part A :High Proteinuria Group - Belimumab and Rituximab
Open-label pharmacokinetics (PK) phase.~Ten 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.~An adjustment (increase) in prescribed weekly dose may occur, per protocol, if indicated by pharmacokinetics (PK) assay results.~High proteinuria classification: The excretion of ≥8 g/day of protein by the kidneys in adults. (Normal in adults: 0.15 g/day).
Experimental: Part B: Low Proteinuria Group - Belimumab and Rituximab
Participants in the low proteinuria classification stratification, based upon Part A, and randomized to this arm, will receive will receive belimumab weekly subcutaneous injections (52 doses administered Week 0 to Week 51) and rituximab infusions at Weeks 4 and 6.
Placebo Comparator: Part B: Low Proteinuria Group - Placebo and Rituximab
Participants in the low proteinuria classification stratification, based upon Part A, and randomized to this arm, will receive will receive belimumab placebo weekly subcutaneous injections (52 doses administered Week 0 to Week 51) and rituximab infusions at Weeks 4 and 6.
Experimental: Part B :High Proteinuria Group - Belimumab and Rituximab
Participants in the high proteinuria classification stratification, based upon Part A, and randomized to this arm, will receive will receive belimumab weekly subcutaneous injections (52 doses administered Week 0 to Week 51) and rituximab infusions at Weeks 4 and 6.~A higher dose of belimumab, per protocol, will be prescribed in high proteinuria participants, if indicated in Part A.
Placebo Comparator: Part A :High Proteinuria Group - Placebo and Rituximab
Participants in the high proteinuria classification stratification, based upon Part A, and randomized to this arm, will receive will receive belimumab placebo weekly subcutaneous injections (52 doses administered Week 0 to Week 51) and rituximab infusions at Weeks 4 and 6.~A higher dose of belimumab placebo, per protocol, will be prescribed in high proteinuria participants, if indicated in Part A.
Sponsors
Collaborators: PPD, GlaxoSmithKline, Rho Federal Systems Division, Inc., Immune Tolerance Network (ITN)
Leads: National Institute of Allergy and Infectious Diseases (NIAID)

This content was sourced from clinicaltrials.gov

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