Kidney Week

Abstract: INFO08-FR

Belimumab and Rituximab Compared with Rituximab Alone for the Treatment of Primary Membranous Nephropathy (REBOOT)

Session Information

• Informational Posters - 2
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• No subcategory defined

Authors

• Chung, Sharon, University of California San Francisco, San Francisco, California, United States

Sharon Chung, MD, MA

• Sherman, Matthew A., National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States

Matthew A. Sherman, MD, MHS

• Nachman, Patrick H., University of Minnesota Medical School, Minneapolis, Minnesota, United States

Patrick H. Nachman, MD, FASN

Group or Team Name

• On behalf of the REBOOT Study Investigators.

Description

Background: Primary membranous nephropathy (MN) is caused by glomerular immune complex deposition, and ~70% of patients produce autoantibodies against the phospholipase A2 receptor (PLA₂R). A substantial unmet need remains for treatment considering the incomplete response rates with current therapies.
Rationale: We hypothesize that treating primary MN with belimumab (BEL, an anti-B cell activating factor monoclonal antibody) and rituximab (RTX, an anti-CD20 monoclonal antibody which depletes B cells) will enhance depletion of memory B cells, limit the re-emergence of autoreactive B cells, and lead to a stronger clinical response.
Study design: REBOOT (NCT03949855) is a clinical trial with 2 parts. Part A, a pharmacokinetic study, is complete. Part B is a phase 2, multicenter, prospective, double-blind, placebo-controlled, clinical effectiveness trial. Participants must be 18-75 years old, and have primary MN, detectable serum anti-PLA₂R, and proteinuria ≥ 4 g/day. 58 participants will be randomized to receive either weekly subcutaneous BEL (n=41) or BEL placebo (n=17) for 52 weeks. All participants will receive 2 doses of RTX at weeks 4 and 6, and those with an insufficient response at week 30 will receive 2 additional doses of RTX at weeks 34 and 36 (Figure 1). The primary outcome of complete or partial remission will be assessed at week 104. Participants will be followed until week 156 to assess for sustained treatment response. Planned mechanistic studies include longitudinal measurement of anti-PLA₂R and functional profiling of autoreactive lymphocytes.
Summary: REBOOT will explore mechanisms of reestablishing immune tolerance in patients with anti-PLA₂R associated primary MN. Part B is currently enrolling. For more information or to refer patients, please visit www.reboot-study.org.

Figure 1. REBOOT Part B study schema.

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). Belimumab and belimumab placebo are provided by GSK plc.