VIBRANT: VIB4920 for Active Lupus Nephritis (VIBRANT)
Lupus Nephritis
About this trial
This is an interventional treatment trial for Lupus Nephritis focused on measuring Lupus Nephritis, Mycophenolate mofetil, VIB4920
Eligibility Criteria
Inclusion Criteria:
Classification of Systemic Lupus Erythematosus (SLE) by any of the following criteria:
- the 1997 update of the 1982 American College of Rheumatology (ACR) criteria
- or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria
- or the 2019 European League Against Rheumatism (EULAR)/ACR criteria
- Urine protein-to-creatinine ratio (UPCR) >=1.5 based on a 24-hour urine collection at Visit -1 or within 14 days prior to Visit -1
Renal biopsy documentation at Visit 1 of ISN/RPS LN with both of the following:
- Class III, Class IV, or Class V in combination with Class III or IV, and
- Modified NIH Activity Index >= 1
Exclusion Criteria:
- Inability or unwillingness to give written informed consent or comply with study protocol
- Contraindication to treatment with mycophenolate mofetil (MMF) or mycophenolate sodium; or treatment with MMF or mycophenolate sodium is inappropriate in the opinion of the investigator
- Treatment with a biologic agent or investigational agent within 90 days or 5 half-lives prior to Visit 0, whichever is longer
- Rituximab or other B cell depleting agent within 6 months prior to Visit 0
- Prior treatment with VIB4920
- Receipt of a live attenuated vaccine within 4 weeks prior to Visit 0
- 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
- 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
- End stage renal disease, defined as Estimated glomerular filtration rate (eGFR) < 20 ml/min/1.73m^2
- History of transplantation
The following risks for thromboembolic events:
- Recent or recurrent deep venous thrombosis or arterial thromboembolism.
- Immobilization or major surgery within 12 weeks prior to Visit 0.
- History of congenital or inherited deficiency of antithrombin III, protein S, or protein C.
- History of anti-phospholipid syndrome.
- Any one of the following anti-phospholipid antibodies:
i. Positive lupus anticoagulant test, or
ii. Anti-beta2-glycoprotein I IgG ELISA titer >= 40 GPL, or
iii. Anti-cardiolipin IgG ELISA titer >= 40 GPL
- History of a severe allergy or hypersensitivity reaction to any component of the VIB4920 formulation
Any one of the following laboratory abnormalities:
- Peripheral B cell count < 5/mcl
- Neutropenia (absolute neutrophil count < 1000/mm^3)
- Anemia (hemoglobin < 8 g/dL)
- Thrombocytopenia (platelets < 50,000/mm^3)
- Aspartate aminotransferase or alanine aminotransferase >= 2x upper limit of normal
Evidence of current or prior tuberculosis infection, including any of the following:
- Positive QuantiFERON-TB Gold or TB Gold Plus test
- Positive T-SPOT.TB test
- Positive purified protein derivation (PPD) tuberculin test, defined as > 5mm induration
- Human immunodeficiency virus (HIV) infection
- Current or past hepatitis B (HBV) infection
- Current or past hepatitis C virus (HCV) infection, except adequately treated HCV with documented sustained virologic response
- Active bacterial, viral, fungal, or opportunistic infection
- History of significant, recurrent, or chronic infection that may pose additional risks from participating in the study, in the opinion of the investigator
- 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
- Current substance abuse, or history of substance abuse within 12 months of Visit 0
- Lack of peripheral venous access
- Pregnancy
- Breastfeeding
- 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 child- bearing potential
- 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
Sites / Locations
- University of California San Diego School of Medicine: Division of Rheumatology, Allergy and Immunology
- UCLA Medical Center: Division of Rheumatology
- University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center
- University of Colorado School of Medicine: Division of Rheumatology
- Yale University School of Medicine: Section of Rheumatology
- University of Miami Miller School of Medicine: Nephrology & Hypertension Division
- Emory University School of Medicine: Division of Rheumatology
- University of Chicago, Department of Medicine: Rheumatology
- University of Minnesota Medical School: Division of Renal Diseases and Hypertension
- Washington University School of Medicine in St. Louis: Division of Nephrology
- Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
- Hospital for Special Surgery, New York: Division of Rheumatology
- Columbia University Medical Center: Department of Medicine, Division of Rheumatology
- Temple University, Lewis Katz School of Medicine, Department of Medicine: Nephrology
- University of South Carolina
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
VIB4920
VIB4920 Placebo
Participants will receive VIB4920 1500 mg intravenously at Weeks 0, 2, 4, 8, 12, 16, 20, and 24. Participants will also receive methylprednisolone 1000 mg at Week 0 and will begin MMF 2-3 g per day and prednisone 25 mg per day, tapered to ≤ 5 mg per day from Week 8.
Participants will receive VIB4920 placebo intravenously at Weeks 0, 2, 4, 8, 12, 16, 20, and 24. Participants will also receive methylprednisolone 1000 mg at Week 0 and will begin MMF 2-3 g per day and prednisone 25 mg per day, tapered to ≤ 5 mg per day from Week 8.