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

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.

Description

Eligibility

Age range

18–75 years

Sex

All

Healthy volunteers

No

Interventions

• Drug
  Belimumab

  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.

• Drug
  Placebo for Belimumab

  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.

• Drug
  Rituximab

  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.

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