Overview

This is a multi-center double-blind placebo controlled clinical trial evaluating the efficacy of VIB4920 combined with mycophenolate mofetil (MMF) and prednisone in achieving a renal response in participants with active lupus nephritis (LN).

Eligibility

Inclusion Criteria:

        Individuals who meet all of the following criteria are eligible for enrollment as study
        participants:
          1. Age 18 years or older.
          2. Classification of Systemic Lupus Erythematosus (SLE) by any of the following criteria:
             the 1997 update of the 1982 American College of Rheumatology (ACR) criteria, the 2012
             Systemic Lupus International Collaborating Clinics (SLICC) criteria, or the 2019
             European League Against Rheumatism (EULAR)/ACR criteria.
          3. UPCR ≥ 1.0 based on a 24-hour urine collection at Visit -1.
          4. Renal biopsy within 24 weeks prior to Visit -1 of ISN/RPS LN with both of the
             following:
               1. Class III, Class IV, or Class V in combination with Class III or IV, and
               2. Modified NIH Activity Index ≥ 1.
        Exclusion Criteria:
        Individuals who meet any of these criteria are not eligible for enrollment as study
        participants:
          1. Inability or unwillingness to give written informed consent or comply with study
             protocol.
          2. Contraindication to treatment with MMF or mycophenolate sodium; or treatment with MMF
             or mycophenolate sodium is inappropriate in the opinion of the investigator.
          3. Treatment with a biologic agent, except belimumab, or investigational agent within 90
             days or 5 half-lives prior to Visit 0, whichever is longer. Agents authorized by the
             FDA for prevention or treatment of COVID-19 are not considered investigational and are
             not exclusionary.
          4. Rituximab or other B cell depleting agent within 6 months prior to Visit 0.
          5. Prior treatment with VIB4920.
          6. Receipt of a live attenuated vaccine within 4 weeks prior to Visit 0.
          7. Comorbidities requiring treatment with systemic corticosteroids, including those that
             have required 3 or more courses of systemic corticosteroids within 12 months prior to
             Visit 0.
          8. Current malignancy or history of malignancy, except for adequately treated basal cell
             carcinoma, squamous cell carcinoma, or cervical carcinoma in situ > 12 months prior to
             Visit 0.
          9. End stage renal disease, defined as eGFR < 20 ml/min/1.73m2.
         10. History of transplantation.
         11. The following risks for thromboembolic events:
               1. Recent or recurrent deep venous thrombosis or arterial thromboembolism.
               2. Immobilization or major surgery within 12 weeks prior to Visit 0.
               3. History of congenital or inherited deficiency of antithrombin III, protein S, or
                  protein C.
               4. History of anti-phospholipid syndrome, according to the 2006 Sapporo
                  classification criteria.
         12. History of a severe allergy or hypersensitivity reaction to any component of the
             VIB4920 formulation.
         13. Any one of the following laboratory abnormalities:
               1. Peripheral B cell count < 5/μl.
               2. Neutropenia (absolute neutrophil count < 1000/mm3).
               3. Anemia (hemoglobin < 8 g/dL).
               4. Thrombocytopenia (platelets < 50,000/mm3).
               5. Aspartate aminiotransferase or alanine aminotransferase ≥ 2x upper limit of
                  normal.
         14. Evidence of current or prior tuberculosis infection, including any of the following:
               1. Positive QuantiFERON-TB Gold or TB Gold Plus test.
               2. Positive T-SPOT.TB test.
               3. Positive purified protein derivation (PPD) tuberculin test, defined as > 5mm
                  induration.
         15. Human immunodeficiency virus (HIV) infection.
         16. Current or past hepatitis B (HBV) infection.
         17. Current or past hepatitis C virus (HCV) infection, except adequately treated HCV with
             documented sustained virologic response.
         18. Active bacterial, viral, fungal, or opportunistic infection.
         19. History of significant, recurrent, or chronic infection that may pose additional risks
             from participating in the study, in the opinion of the investigator.
         20. History of severe psychiatric condition that would interfere with the participant's
             ability to comply with the study protocol, in the opinion of the investigator.
         21. Current substance abuse, or history of substance abuse within 12 months of Visit 0.
         22. Lack of peripheral venous access.
         23. Pregnancy.
         24. Breastfeeding.
         25. Unwillingness to use a medically acceptable form of contraception for the duration of
             the study if female of child-bearing potential or if male with a partner of
             childbearing potential.
         26. Past or current medical problems or findings from physical examination or laboratory
             testing that are not listed above, which, in the opinion of the investigator, may pose
             additional risks from participation in the study, may interfere with the participant's
             ability to comply with study requirements or that may impact the quality or
             interpretation of the data obtained from the study.