REBOOT is a two-part clinical study of adults with primary membranous nephropathy that will investigate whether belimumab and rituximab is safe and more effective at blocking the immune attack on the kidneys compared to rituxumab alone
Part A is an open-label PK (pharmacokinetic) study to compare belimumab exposure between participants who have "low" proteinuria between 4-8g/day and "high" proteinuria more than 8g/day. If belimumab exposure levels is not comparable between the low and high proteinuria groups, the belimumab dose will be increased for participants with high proteinuria during Part B of the study. Participants in Part A will also receive rituxumab.
Part B is a prospective, randomized, phase II, double-blind, placebo-controlled, multicenter clinical trial in adults with primary membranous nephropathy. Participants will be randomized to two treatment arms. Both arms will receive rituximab at weeks 4 and 6. Participants in the experimental arm will receive belimumab weekly for 52 doses. Participants in the control arm will receive a weekly placebo in the place of belimumab. After 52 weeks, all participants will be followed on no study medication and then assessed for the primary endpoint of complete remission at week 104 and at week 156 to determine if treatment with belimumab and rituximab results in a more durable remission than rituximab alone.
About This Study
Primary membranous nephropathy (Primary MN) is a disease that causes damage to the parts of the kidney that filter the blood, called the glomeruli. Damage to these filters can lead to high levels of protein in the urine, as well as reduced kidney function. If untreated, about half of patients with nephrotic syndrome will eventually develop kidney failure, also known as end stage renal disease.
The Study Drug
In REBOOT, researchers are testing whether a combination of two different drugs, belimumab and rituximab, is safe and if this combination is more effective at blocking the immune attack on the kidney compared to rituximab alone.
Rituximab is a medication that works by blocking B cells (an immune cell that is known to have a role in autoimmune diseases like Primary MN). Rituximab is approved by the FDA for use in rheumatoid arthritis, vasculitis, and certain types of cancers. A few studies have shown that rituximab can be effective in treating some people with Primary MN, but is not FDA approved for Primary MN.
Belimumab is a medication that blocks different types of B cells than rituximab. Belimumab is approved by the FDA for systemic lupus erythematosus (SLE).
REBOOT is a two-part clinical study:
People with Primary MN lose more protein in their urine because the filters in their kidneys may be damaged. It is possible that some belimumab may also be lost in the urine because of this. To make up for this loss, people with higher levels of protein in their urine may need a higher dose of belimumab than the FDA approved dose. One purpose of Part A is to measure belimumab in the blood to determine if people with more protein in their urine should receive a higher dose of belimumab.
All Part A participants will receive belimumab injections under the skin (subcutaneously) once a week for 1 year. They will also receive an infusion of rituximab at the 4th and 6th week of the study. Participants will then be followed for an additional 2 years to determine if Primary MN gets better or worse after stopping study treatment.
Part B participants will be randomly assigned to 1 of 2 treatment groups. You cannot choose your group. A computer will randomly pick which group you will be in.
One group will receive weekly belimumab for 1 year. The other group will receive weekly placebo for 1 year. All participants will receive intravenous (IV) rituximab at weeks 4 and 6. Participants will be followed for an additional 2 years to determine if Primary MN gets better or worse after stopping study treatment and to determine if treatment with belimumab and rituximab results in a more durable remission than rituximab alone.
Do you Qualify for this Clinical Trial?
You may be eligible to participate in REBOOT if you:
Are 18 to 75 years old
Have been diagnosed with primary membranous neuropathy