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Abstract: INFO32

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

Session Information

  • Informational Posters
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • No subcategory defined

Authors

  • Nachman, Patrick H., University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, United States
  • Chung, Sharon, Immune Tolerance Network, San Francisco, California, United States
  • Ding, Linna, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States

Group or Team Name

  • on behalf of the REBOOT study 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, the rate of CR remains low.
Rationale: This study examines whether combining B-cell targeting therapy results in greater clinical efficacy in PMN. We hypothesize that treating patients with PMN with both rituximab (RTX, a B-cell depleting agent) and belimumab (BEL, a 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, two-part clinical trial (Figure 1). Part A, an open-label study, examines how baseline proteinuria affects BEL exposure. In Part B, a prospective, double-blind, placebo-controlled trial, 104 participants will receive 2 doses of RTX and be randomized to receive weekly subcutaneous BEL or placebo for 52 weeks. Participants will be followed on no study medication until week 156. Participants must be 18-75 years old with circulating 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 a 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 PMN. Part A is completed, and Part B is actively enrolling. For additional information and to refer patients, please visit www.reboot-study.org.

Figure 1. Study Design

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.
Abstract: INFO32

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

Session Information

  • Informational Posters
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category:

  • No subcategory defined

Authors

  • Nachman, Patrick H., University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, United States
  • Chung, Sharon, Immune Tolerance Network, San Francisco, California, United States
  • Ding, Linna, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States
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, the rate of CR remains low.
Rationale: This study examines whether combining B-cell targeting therapy results in greater clinical efficacy in PMN. We hypothesize that treating patients with PMN with both rituximab (RTX, a B-cell depleting agent) and belimumab (BEL, a 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, two-part clinical trial (Figure 1). Part A, an open-label study, examines how baseline proteinuria affects BEL exposure. In Part B, a prospective, double-blind, placebo-controlled trial, 104 participants will receive 2 doses of RTX and be randomized to receive weekly subcutaneous BEL or placebo for 52 weeks. Participants will be followed on no study medication until week 156. Participants must be 18-75 years old with circulating 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 a 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 PMN. Part A is completed, and Part B is actively enrolling. For additional information and to refer patients, please visit www.reboot-study.org.

Figure 1. Study Design

Abstract: INFO32

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

Session Information

  • Informational Posters
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category:

  • No subcategory defined

Authors

  • Nachman, Patrick H., University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, United States
  • Chung, Sharon, Immune Tolerance Network, San Francisco, California, United States
  • Ding, Linna, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States
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, the rate of CR remains low.
Rationale: This study examines whether combining B-cell targeting therapy results in greater clinical efficacy in PMN. We hypothesize that treating patients with PMN with both rituximab (RTX, a B-cell depleting agent) and belimumab (BEL, a 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, two-part clinical trial (Figure 1). Part A, an open-label study, examines how baseline proteinuria affects BEL exposure. In Part B, a prospective, double-blind, placebo-controlled trial, 104 participants will receive 2 doses of RTX and be randomized to receive weekly subcutaneous BEL or placebo for 52 weeks. Participants will be followed on no study medication until week 156. Participants must be 18-75 years old with circulating 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 a 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 PMN. Part A is completed, and Part B is actively enrolling. For additional information and to refer patients, please visit www.reboot-study.org.

Figure 1. Study Design