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Abstract: INFO25

A Phase 2a Trial of VIB4920 for Active Lupus Nephritis (VIBRANT)

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

  • Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Diamond, Betty, Northwell Health Feinstein Institutes for Medical Research, Manhasset, New York, United States
  • Wofsy, David, University of California San Francisco, San Francisco, California, United States
  • Smilek, Dawn E., Immune Tolerance Network, San Francisco, California, United States
  • Ding, Linna, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States
  • Dall'Era, Maria, University of California San Francisco, San Francisco, California, United States

Group or Team Name

  • VIBRANT Study Team
Description

Background: Lupus nephritis (LN) is an organ-threatening manifestation of systemic lupus erythematosus. Current therapies show only partial efficacy, substantial toxicity, and poor adherence. There is a critical unmet need in LN for effective therapeutics with less toxicity.
Rationale: CD40 and CD40L are co-stimulatory molecules important for T cell-dependent B cell activation and germinal center formation. VIB4920 is a novel engineered fusion protein that antagonizes CD40L. It lacks an Fc domain, avoiding the mechanism thought responsible for inducing thromboembolic complications observed with previous CD40/CD40L pathway antagonists. VIB4920 showed safety and tolerability in a phase 1b clinical trial in rheumatoid arthritis (PMID: 31019027).
Study Design: The VIBRANT trial (NCT05201469) is a proof of concept study of the efficacy and safety of VIB4920 in LN. Up to 114 participants with active LN will undergo a kidney biopsy with collection of a research core at baseline, followed by therapy with standard doses of mycophenolate mofetil (MMF), methylprednisolone, and a rapid glucocorticoid (GC) taper to 5 mg prednisone/d. Participants will be assessed for response at week 8. Sixty-six participants with an inadequate renal response, defined as urine protein to creatinine ratio > 0.75, will be randomized 2:1 to VIB4920 or placebo, plus continued MMF and low-dose GC. The primary endpoint of complete renal response will be assessed at Week 38. A repeat kidney biopsy will be obtained to assess histological changes and to test the hypothesis that VIB4920 will reduce activated B cells in the LN kidney by interfering with B cell activation through blockade of the CD40:CD40L costimulatory pathway. Enrollment May 2022-2025 . Additional information: http://www.vibrant-study.org/

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). Horizon Therapeutics is providing VIB4920.
Abstract: INFO25

A Phase 2a Trial of VIB4920 for Active Lupus Nephritis (VIBRANT)

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

  • Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Diamond, Betty, Northwell Health Feinstein Institutes for Medical Research, Manhasset, New York, United States
  • Wofsy, David, University of California San Francisco, San Francisco, California, United States
  • Smilek, Dawn E., Immune Tolerance Network, San Francisco, California, United States
  • Ding, Linna, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States
  • Dall'Era, Maria, University of California San Francisco, San Francisco, California, United States
Description

Background: Lupus nephritis (LN) is an organ-threatening manifestation of systemic lupus erythematosus. Current therapies show only partial efficacy, substantial toxicity, and poor adherence. There is a critical unmet need in LN for effective therapeutics with less toxicity.
Rationale: CD40 and CD40L are co-stimulatory molecules important for T cell-dependent B cell activation and germinal center formation. VIB4920 is a novel engineered fusion protein that antagonizes CD40L. It lacks an Fc domain, avoiding the mechanism thought responsible for inducing thromboembolic complications observed with previous CD40/CD40L pathway antagonists. VIB4920 showed safety and tolerability in a phase 1b clinical trial in rheumatoid arthritis (PMID: 31019027).
Study Design: The VIBRANT trial (NCT05201469) is a proof of concept study of the efficacy and safety of VIB4920 in LN. Up to 114 participants with active LN will undergo a kidney biopsy with collection of a research core at baseline, followed by therapy with standard doses of mycophenolate mofetil (MMF), methylprednisolone, and a rapid glucocorticoid (GC) taper to 5 mg prednisone/d. Participants will be assessed for response at week 8. Sixty-six participants with an inadequate renal response, defined as urine protein to creatinine ratio > 0.75, will be randomized 2:1 to VIB4920 or placebo, plus continued MMF and low-dose GC. The primary endpoint of complete renal response will be assessed at Week 38. A repeat kidney biopsy will be obtained to assess histological changes and to test the hypothesis that VIB4920 will reduce activated B cells in the LN kidney by interfering with B cell activation through blockade of the CD40:CD40L costimulatory pathway. Enrollment May 2022-2025 . Additional information: http://www.vibrant-study.org/

Abstract: INFO25

A Phase 2a Trial of VIB4920 for Active Lupus Nephritis (VIBRANT)

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

  • Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Diamond, Betty, Northwell Health Feinstein Institutes for Medical Research, Manhasset, New York, United States
  • Wofsy, David, University of California San Francisco, San Francisco, California, United States
  • Smilek, Dawn E., Immune Tolerance Network, San Francisco, California, United States
  • Ding, Linna, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States
  • Dall'Era, Maria, University of California San Francisco, San Francisco, California, United States
Description

Background: Lupus nephritis (LN) is an organ-threatening manifestation of systemic lupus erythematosus. Current therapies show only partial efficacy, substantial toxicity, and poor adherence. There is a critical unmet need in LN for effective therapeutics with less toxicity.
Rationale: CD40 and CD40L are co-stimulatory molecules important for T cell-dependent B cell activation and germinal center formation. VIB4920 is a novel engineered fusion protein that antagonizes CD40L. It lacks an Fc domain, avoiding the mechanism thought responsible for inducing thromboembolic complications observed with previous CD40/CD40L pathway antagonists. VIB4920 showed safety and tolerability in a phase 1b clinical trial in rheumatoid arthritis (PMID: 31019027).
Study Design: The VIBRANT trial (NCT05201469) is a proof of concept study of the efficacy and safety of VIB4920 in LN. Up to 114 participants with active LN will undergo a kidney biopsy with collection of a research core at baseline, followed by therapy with standard doses of mycophenolate mofetil (MMF), methylprednisolone, and a rapid glucocorticoid (GC) taper to 5 mg prednisone/d. Participants will be assessed for response at week 8. Sixty-six participants with an inadequate renal response, defined as urine protein to creatinine ratio > 0.75, will be randomized 2:1 to VIB4920 or placebo, plus continued MMF and low-dose GC. The primary endpoint of complete renal response will be assessed at Week 38. A repeat kidney biopsy will be obtained to assess histological changes and to test the hypothesis that VIB4920 will reduce activated B cells in the LN kidney by interfering with B cell activation through blockade of the CD40:CD40L costimulatory pathway. Enrollment May 2022-2025 . Additional information: http://www.vibrant-study.org/