Health TrialsbyHealthPanel

Belimumab With Rituximab for Primary Membranous Nephropathy

ConditionsMembranous NephropathyNephrotic Syndrome
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18 to 75 years inclusive

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

Disqualifiers

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

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Belimumab

    Drug

    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.

  • Placebo for Belimumab

    Drug

    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

    Drug

    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.

Treatment groups

58 Participants
are divided into 4 treatment groups
Group A: Part A: Low Proteinuria Group - Belimumab and RituximabExperimental treatment 2 interventions
Group B: Part A :High Proteinuria Group - Belimumab and RituximabExperimental treatment 2 interventions
Group C: Part B: Belimumab and RituximabExperimental treatment 2 interventions
Group D: Part B: Placebo and RituximabPlacebo comparator 2 interventions

Trial outcomes

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.

Time frame
Week 104

Secondary outcomes

1

Proportion of Participants in Complete or Partial Remission (CR or PR) at Week 52 and Week 156.

Time frame
Week 52, Week 156
2

Proportion of Participants in Complete Remission (CR) at Week 52, Week 104 and Week 156.

Time frame
Week 52, Week 104, Week 156
3

Proportion of Participants in PR but not CR at Week 52, Week 104, Week 156.

Time frame
Week 52, Week 104, Week 156
4

Time to Relapse for Participants who Achieved CR or PR.

Time frame
Up to 156 Weeks (3 Years)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Institute of Allergy and Infectious Diseases (NIAID)

Lead sponsor

Immune Tolerance Network (ITN)

Collaborator

GlaxoSmithKline

Collaborator

PPD Development, LP

Collaborator

Rho Federal Systems Division, Inc.

Collaborator

Source ClinicalTrials.gov
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