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 (20) 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 has been 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: f
View:

∙ 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

Locations
United States
Alabama
University of Alabama at Birmingham School of Medicine: Division of Nephrology
RECRUITING
Birmingham
Arkansas
University of Arkansas
RECRUITING
Little Rock
California
University of California San Francisco
RECRUITING
San Francisco
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
Colorado
University of Colorado
RECRUITING
Aurora
Florida
Mayo Clinic Jacksonville: Department of Nephrology and Hypertension
RECRUITING
Jacksonville
University of Miami Miller School of Medicine, Div of Nephrology
RECRUITING
Miami
Maryland
Johns Hopkins
RECRUITING
Baltimore
National Institutes of Health Clinical Center
RECRUITING
Bethesda
Michigan
University of Michigan
RECRUITING
Ann Arbor
Minnesota
University of Minnesota Health Clinical Research Unit
RECRUITING
Minneapolis
Missouri
Washington University in St. Louis
RECRUITING
St Louis
North Carolina
University of North Carolina School of Medicine: Division of Nephrology and Hypertension, Kidney Center
RECRUITING
Chapel Hill
Nebraska
University of Nebraska
RECRUITING
Omaha
New York
Columbia University Medical Center: Division of Nephrology
RECRUITING
New York
Ohio
Cleveland Clinic
RECRUITING
Cleveland
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
Washington
Providence Medical Research Center, Providence Health Care: Nephrology
RECRUITING
Spokane
Time Frame
Start Date: 2020-03-06
Estimated Completion Date: 2030-03-01
Participants
Target number of participants: 58
Treatments
Experimental: Part A: Low Proteinuria Group - Belimumab and Rituximab
Open-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).
Experimental: Part A :High Proteinuria Group - Belimumab and Rituximab
Open-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).
Experimental: Part B: Belimumab and Rituximab
Participants 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
Placebo_comparator: Part B: Placebo and Rituximab
Participants 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
Sponsors
Collaborators: Rho Federal Systems Division, Inc., PPD Development, LP, Immune Tolerance Network (ITN), GlaxoSmithKline
Leads: National Institute of Allergy and Infectious Diseases (NIAID)

This content was sourced from clinicaltrials.gov