VIBRANT: VIB4920 for Active Lupus Nephritis (VIBRANT)

December 17, 2025 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase 2a Randomized Placebo-Controlled Double-Blind Multicenter Trial of VIB4920 for Active Lupus Nephritis (ITN091AI)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Seventy-four eligible participants with active lupus nephritis (LN) will be randomized to receive VIB4920 1500 mg or placebo intravenously at Weeks 0, 2, 4, 8, 12, 16, 20, and 24. Participants will receive a total of 1000 mg of methylprednisolone according to either of the following schedules:

  • 1000 mg methylprednisolone IV at Day 0, or
  • 500 mg methylprednisolone IV at Day 0 and at Day 1.

Participants who previously received 1000 mg of methylprednisolone IV within 42 days of Visit 0 will not receive additional methylprednisolone IV on Day 0. Participants who previously received less than 1000 mg of methylprednisolone IV within 42 days of Visit 0 will receive an additional dose of methylprednisolone IV at Day 0, according to the following formula, where X is the intravenous dose previously received and Y is the intravenous dose administered on Day 0: 1000 mg - X = Y. Participants will also receive MMF 2-3 g per day and will receive prednisone 25 mg/d beginning on Day 0, or on the day after completion of methylprednisolone. Prednisone will be tapered to 5 mg/d by Week 8.

Study Type

Interventional

Enrollment (Estimated)

74

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • University of California San Diego School of Medicine: Division of Rheumatology, Allergy and Immunology
        • Principal Investigator:
          • Kenneth Kalunian
        • Contact:
        • Contact:
      • Los Angeles, California, United States, 90095
        • Recruiting
        • UCLA Medical Center: Division of Rheumatology
        • Principal Investigator:
          • Maureen McMahon
        • Contact:
        • Contact:
      • Orange, California, United States, 92868
        • Recruiting
        • of California, Irvine School of Medicine Division of Rheumatology
        • Contact:
        • Principal Investigator:
          • Desai Sheetal
        • Contact:
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center
        • Principal Investigator:
          • Maria Dall'Era
        • Contact:
        • Contact:
    • Colorado
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Recruiting
        • Yale University School of Medicine: Section of Rheumatology
        • Principal Investigator:
          • Fotios Koumpouras
        • Contact:
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Miller School of Medicine: Nephrology & Hypertension Division
        • Principal Investigator:
          • Gabriel Contreras
        • Contact:
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30307
        • Recruiting
        • Emory University School of Medicine: Division of Rheumatology
        • Principal Investigator:
          • Arezou Khosroshahi, MD
        • Contact:
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago, Department of Medicine: Rheumatology
        • Principal Investigator:
          • Kichul Ko
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Principal Investigator:
          • Panduranga Rao
        • Contact:
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine in St. Louis: Division of Nephrology
        • Principal Investigator:
          • Tingting Li
        • Contact:
    • New York
      • Manhasset, New York, United States, 11030
        • Recruiting
        • Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
        • Contact:
        • Principal Investigator:
          • Cynthia Aranow, MD
        • Contact:
      • New York, New York, United States, 10021
        • Not yet recruiting
        • Hospital for Special Surgery, New York: Division of Rheumatology
        • Principal Investigator:
          • Kirou Kyriakos
        • Contact:
        • Contact:
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center: Department of Medicine, Division of Rheumatology
        • Principal Investigator:
          • Anca Askanase
        • Contact:
        • Contact:
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Recruiting
        • Penn State Health Milton S. Hershey Medical Center: Division of Rheumatology
        • Contact:
        • Principal Investigator:
          • Nancy Olsen
        • Contact:
          • Phone Number: 215-615-4938
      • Philadelphia, Pennsylvania, United States, 19140
        • Recruiting
        • Temple University, Lewis Katz School of Medicine, Department of Medicine: Nephrology
        • Principal Investigator:
          • Iris Lee
        • Contact:
        • Contact:
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • University of South Carolina
        • Principal Investigator:
          • Diane Kamen
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 or within 14 days prior to 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.
  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. ESRD, 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VIB4920

Participants will receive VIB4920 1500 mg intravenously at Weeks 0, 2, 4, 8, 12, 16, 20, and 24.

Participants who previously received 1000 mg of methylprednisolone IV within 42 days of Visit 0 will not receive additional methylprednisolone IV on Day 0. Participants who previously received less than 1000 mg of methylprednisolone IV within 42 days of Visit 0 will receive an additional dose of methylprednisolone IV at Day 0, according to the following formula, where X is the intravenous dose previously received and Y is the intravenous dose administered on Day 0: 1000 mg - X = Y. Participants will begin MMF 2-3 g per day and prednisone 25 mg per day, tapered to 5 mg per day by Week 8. The prednisone dose may be tapered more rapidly and to a dose lower than 5 mg/d, at the discretion of the site investigator. Prednisone of no more than 5 mg/d will be continued until Week 60.
Drug: VIB4920
Participants will receive 1500 mg of VIB4920 at Weeks 0, 2, 4, 8, 12, 16, 20, and 24 while continuing on MMF and prednisone
Placebo Comparator: VIB4920 Placebo

Participants will receive VIB4920 placebo intravenously at Weeks 0, 2, 4, 8, 12, 16, 20, and 24.

Participants who previously received 1000 mg of methylprednisolone IV within 42 days of Visit 0 will not receive additional methylprednisolone IV on Day 0. Participants who previously received less than 1000 mg of methylprednisolone IV within 42 days of Visit 0 will receive an additional dose of methylprednisolone IV at Day 0, according to the following formula, where X is the intravenous dose previously received and Y is the intravenous dose administered on Day 0: 1000 mg - X = Y. Participants will begin MMF 2-3 g per day and prednisone 25 mg per day, tapered to 5 mg per day by Week 8. The prednisone dose may be tapered more rapidly and to a dose lower than 5 mg/d, at the discretion of the site investigator. Prednisone of no more than 5 mg/d will be continued until Week 60.
Drug: Placebo for VIB4920
Participants will receive placebo for VIB4920 at Weeks 0, 2, 4, 8, 12, 16, 20, and 24 while continuing on MMF and prednisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants achieving a complete renal response at week 36
Time Frame: Week 36

Complete renal response is defined as all of the following:

  1. Urine protein-to-creatinine ratio (UPCR) <= 0.5, based on a 24-hour urine collection
  2. Estimated glomerular filtration rate (eGFR) >= 120 ml/min/1.73 m^2 or, if < 120 ml/min/1.73 m^2, then >= 80 percent of the eGFR at baseline
  3. Prednisone <= 5 mg/day from Week 8, according to the prednisone dosing restrictions
Week 36

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who experience at least one serious adverse event
Time Frame: Week 0 to Week 60
The number of participants who experienced at least one SAE and the number of participants who experienced at least one AESI will be analyzed using a Fisher's exact test.
Week 0 to Week 60
Proportion of participants who achieve a complete renal response
Time Frame: Weeks 12, 24, 48, and 60

Complete renal response is defined as all of the following:

  1. Urine protein-to-creatinine ratio (UPCR) <= 0.5, based on a 24-hour urine collection
  2. Estimated glomerular filtration rate (eGFR) >= 120 ml/min/1.73 m^2 or, if < 120 ml/min/1.73 m^2, then > 80 percent of the eGFR at Week 0
  3. Prednisone tapered to <= 5 mg/day by Week 8, and adherence to the prednisone dosing restrictions
Weeks 12, 24, 48, and 60
Proportion of participants who achieve an overall renal response
Time Frame: Weeks 12, 24, 36, 48 and 60

Overall renal response is defined as all of the following:

  1. >= 50 percent improvement in the urine protein-to-creatinine ratio (UPCR) compared to baseline, based on a 24-hour urine collection
  2. Estimated glomerular filtration rate (eGFR) >= 120 ml/min/1.73 m^2, or if < 120 ml/min/1.73 m^2, then > 80 percent of the eGFR at baseline, and
  3. Prednisone <= 5 mg/day from Week 8, according to the prednisone dosing restrictions
Weeks 12, 24, 36, 48 and 60
Change in Serum IgM over study participation
Time Frame: Weeks 12, 24, 36, 48, and 60
Serum IgM levels will be analyzed using a longitudinal mixed effects model with the test results at the time points as the dependent variable
Weeks 12, 24, 36, 48, and 60
Urine Protein-to-Creatinine Ratio (UPCR)
Time Frame: Weeks 12, 24, 36, 48, and 60
Based on 24-hour urine collection
Weeks 12, 24, 36, 48, and 60
Proportion of participants who achieve a BLISS-LN primary efficacy renal response (PERR)
Time Frame: Weeks 12, 24, 36, 48, and 60

BLISS-LN primary efficacy renal response (PERR) defined as all of the following:

  1. UPCR ≤ 0.7, and
  2. eGFR ≥ 60 ml/min/1.73m2, or if < 60 ml/min/1.73m2, then ≥ 80% of the eGFR at baseline, and
  3. no receipt of a prohibited immunosuppressive or immunomodulatory medication
Weeks 12, 24, 36, 48, and 60
Anti-dsDNA antibodies
Time Frame: Weeks 12, 24, 36, 48, and 60
The change in the proportion of participants who had a negative anti-dsDNA test will be summarized by arm, and will be analyzed using an exact conditional logistic regression model
Weeks 12, 24, 36, 48, and 60
Change in proportion of participants with lower C3 levels after treatment initiation
Time Frame: Weeks 12, 24, 36, 48, and 60
The change in the proportion of participants who were hypocomplementemic for C3 and C4 after initiation of VIB4920 or placebo will be summarized by arm, and analyzed using an exact conditional logistic regression model
Weeks 12, 24, 36, 48, and 60
Change in proportion of participants with lower C4 levels after treatment initiation
Time Frame: Weeks 12, 24, 36, 48, and 60
The change in the proportion of participants who were hypocomplementemic for C3 and C4 after initiation of VIB4920 or placebo will be summarized by arm, and analyzed using an exact conditional logistic regression model
Weeks 12, 24, 36, 48, and 60
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
Time Frame: Weeks 12, 24, 36, 48, and 60
The change in SLEDAI-2K scores after initiation of VIB4920 or placebo will be summarized by arm, and analyzed using an analysis of covariance (ANCOVA) model
Weeks 12, 24, 36, 48, and 60
Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus (SLICC/ACR-DI)
Time Frame: Weeks 24 and 60
The change in SLICC/ACR-DI scores after initiation of VIB4920 or placebo will be summarized by arm, and analyzed using an ANCOVA model
Weeks 24 and 60
Number of participants who experience at least one adverse Events of Special Interest
Time Frame: Week 0 to Week 60

Adverse Events of Special Interests include:

  1. Anaphylaxis
  2. Grade 3 or greater infusion reaction
  3. Grade 3 or greater hypersensitivity reaction
  4. Grade 3 or greater infection
  5. Thromboembolic event
Week 0 to Week 60
Change in Serum IgG over study participation
Time Frame: Weeks 12, 24, 36, 48, and 60
Serum IgG levels will be analyzed using a longitudinal mixed effects model with the test results at the time points as the dependent variable
Weeks 12, 24, 36, 48, and 60
Proportion of participants who experience treatment failures
Time Frame: Week 0 to Week 60

Treatment failure is defined as any one of the following:

  1. Receipt of SLE rescue therapy
  2. End-stage renal disease (ESRD), defined as eGFR < 20 ml/min/1.73m2

  3. Worsening of proteinuria or eGFR from Week 24 onward, defined as either:

    1. confirmed ≥ 50% increase in the UPCR to a value ≥ 3.0 compared to Visit -1, or
    2. confirmed ≥ 30% increase in eGFR to a value of < 60, compared to Visit -1
Week 0 to Week 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Maria Dall'Era, M.D., University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center
  • Study Chair: Betty Diamond, M.D., Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
  • Study Chair: David Wofsy, M.D., University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 16, 2022

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

January 7, 2022

First Submitted That Met QC Criteria

January 7, 2022

First Posted (Actual)

January 21, 2022

Study Record Updates

Last Update Posted (Estimated)

December 19, 2025

Last Update Submitted That Met QC Criteria

December 17, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAIT ITN091AI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical mechanistic data from NIAID/DAIT-funded grants and contracts

IPD Sharing Time Frame

Within 24 months after database lock for the trial

IPD Sharing Access Criteria

Open Access

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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