Abstract: INFO15-SA
Efficacy of Belimumab and Rituximab Compared with Rituximab Alone for the Treatment of Primary Membranous Nephropathy (REBOOT)
Session Information
- Informational Posters - III
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Nachman, Patrick H., University of Minnesota, Minneapolis, Minnesota, United States
- Ding, Linna, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States
Group or Team Name
- on behalf of the ITN080AI REBOOT Study Management Team
Description
Background: Primary membranous nephropathy (PMN) is caused by the glomerular deposition of immune complexes. Autoantibodies against the phospholipase A2 receptor (PLA2R) are identified in ~70% of patients with PMN. In PMN, complete remission (CR) of proteinuria is associated with a low rate of relapse and excellent patient and kidney outcomes. With current therapies, rate of CR remains low.
Rationale: We hypothesize that treating patients with PMN with both rituximab (RTX, a B-cell depleting agent) and belimumab (BEL, monoclonal antibody directed against B cell activating factor) will result in greater depletion of memory B cells, limit the re-emergence of autoreactive B cells, and lead to a more sustained response.
Study design: REBOOT (NCT03949855) is a phase 2, multicenter, a prospective, double-blind, placebo-controlled trial. 104 participants will receive weekly subcutaneous BEL or placebo for 52 weeks and 2 doses of RTX at weeks 4 and 6. Participants meeting certain response criteria at week 30 will receive 2 additional doses of RTX at weeks 34 and 36. Participants will be followed until week 156 (Figure 1). Patients must be 18-75 years old with serum anti-PLA2R positive PMN and have proteinuria ≥ 4 g/day. The primary outcome is the proportion of participants in complete remission (proteinuria ≤ 0.3 g/day with stable eGFR) at week 104. The tolerance endpoint at week 156 assesses whether treatment with BEL and RTX results in a more durable remission compared to RTX alone. Planned mechanistic studies include longitudinal measurement of anti-PLA2R antibodies and functional profiling of autoreactive lymphocytes.
Summary: REBOOT is designed to explore mechanisms of reestablishing immune tolerance in patients with anti-PLA2R associated primary MN. For additional information or to refer patients, please visit www.reboot-study.org.
Figure 1. Study Design
Funding
- Funding: Conducted by the Immune Tolerance Network and supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (UM1-AI-109565). GSK plc is providing belimumab.