VIBRANT: VIB4920 for Active Lupus Nephritis (VIBRANT)

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: Lupus Nephritis
• Intervention / Treatment: Drug: VIB4920; Drug: Placebo for VIB4920

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 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. The primary endpoint will be assessed at Week 36, and participants followed until Week 60.

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Not yet recruiting
      • University of California San Diego School of Medicine: Division of Rheumatology, Allergy and Immunology
      • Contact: Erica Brodie; Phone Number: 858-246-2386; Email: ebrodie@health.ucsd.edu
      • Principal Investigator: Kenneth Kalunian
      • Contact: Amina Arshad; Phone Number: 858-246-2389; Email: aiarshad@health.ucsd.edu
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • UCLA Medical Center: Division of Rheumatology
      • Principal Investigator: Maureen McMahon
      • Contact: Lori Sahakian; Phone Number: 310-794-9236; Email: Lsahakian@mednet.ucla.edu
      • Contact: Belen Ramirez; Phone Number: 310-825-2598; Email: BelenRamirez@mednet.ucla.edu
    • Orange, California, United States, 92868
      • Not yet recruiting
      • University of California, Irvine School of Medicine Division of Rheumatology
      • Contact: Bryan Robles; Email: bsrobles@hs.uci.edu
      • Contact: Walid Roshan; Email: ahmadwar@hs.uci.edu
      • Principal Investigator: Desai Sheetal
    • 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: Lidia Espino; Phone Number: 415-502-5108; Email: Lidia.Espino@ucsf.edu
      • Contact: Olivia Rosenstein; Phone Number: 415-502-1886; Email: olivia.rosenstein@ucsf.edu
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado School of Medicine: Division of Rheumatology
      • Principal Investigator: Amber Podoll
      • Contact: Elizabeth Wagner; Phone Number: 303-724-7790; Email: elizabeth.c.wagner@cuanschutz.edu
      • Contact: Jennyleigh Santa Rosa; Email: Jennyleigh.santarosa@cuanschutz.edu
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Yale University School of Medicine: Section of Rheumatology
      • Contact: Julie Heffernan; Phone Number: 203-785-6631; Email: julie.heffernan@yale.edu
      • Principal Investigator: Fotios Koumpouras
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Miller School of Medicine: Nephrology & Hypertension Division
      • Principal Investigator: Gabriel Contreras
      • Contact: Carlos Bidot; Phone Number: 305-243-8793; Email: cbidot2@med.miami.edu
      • Contact: Miguel Bandes; Email: mab816@med.miami.edu
  • Georgia
    • Atlanta, Georgia, United States, 30307
      • Recruiting
      • Emory University School of Medicine: Division of Rheumatology
      • Contact: John Varghese; Phone Number: 404-727-2886; Email: john.varghese@emory.edu
      • Principal Investigator: Arezou Khosroshahi, MD
      • Contact: Sabeena Usman; Email: sabeena.usman@emory.edu
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago, Department of Medicine: Rheumatology
      • Principal Investigator: Kichul Ko
      • Contact: Sarah Gonzalez; Phone Number: 773-702-1229; Email: sarah.gonzalez@bsd.uchicago
      • Contact: Yusra Irshad; Phone Number: 773-702-5119; Email: yusra.irshad@bsd.uchicago.edu
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine in St. Louis: Division of Nephrology
      • Principal Investigator: Tingting Li
      • Contact: Audrey Stratemeyer; Phone Number: 314-362-8749; Email: audreys@wustl.edu
      • Contact: Brittany Zwijack; Phone Number: 314-747-8251; Email: bzwijack@wustl.edu
  • New York
    • Manhasset, New York, United States, 11030
      • Recruiting
      • Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
      • Principal Investigator: Cynthia Aranow, MD
      • Contact: Sanita Kandasami; Phone Number: 516-562-2401; Email: skandasami@northwell.edu
    • New York, New York, United States, 10021
      • Not yet recruiting
      • Hospital for Special Surgery, New York: Division of Rheumatology
      • Principal Investigator: Kirou Kyriakos
      • Contact: Emily Wu; Phone Number: 212-774-2967; Email: WuE@HSS.edu
      • Contact: Haley Slosberg; Email: slosbergh@hss.edu
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center: Department of Medicine, Division of Rheumatology
      • Principal Investigator: Anca Askanase
      • Contact: Sean Inzerillo; Phone Number: 212-342-9051; Email: si2404@cumc.columbia.edu
      • Contact: Maya Souvignier; Email: mls2356@cumc.columbia.edu
  • Ohio
    • Columbus, Ohio, United States, 43201
      • Not yet recruiting
      • Ohio State University
      • Contact: Laci Roberts; Phone Number: 614-685-5323; Email: laci.roberts@osumc.edu
      • Contact: Alexander McDaniels; Phone Number: 614 -293-9904; Email: alexander.mcdaniels@osumc.edu
      • Principal Investigator: Isabelle Ayoub
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Not yet recruiting
      • Penn State Health Milton S. Hershey Medical Center: Division of Rheumatology
      • Contact: Peri Newman; Phone Number: 717-531-4921; Email: pnewman@pennstatehealth.psu.edu
      • Contact: Jamie Carter; Phone Number: 717-531-4921; Email: jcarter3@pennstatehealth.psu.edu
      • Principal Investigator: Nancy Olsen
    • Philadelphia, Pennsylvania, United States, 19140
      • Not yet recruiting
      • Temple University, Lewis Katz School of Medicine, Department of Medicine: Nephrology
      • Principal Investigator: Iris Lee
      • Contact: Julia Aruta; Email: julia.aruta@temple.edu
      • Contact: Zoe Pfeffer; Phone Number: 267-242-2902; Email: zoe.pfeffer@tuhs.temple.edu
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • University of South Carolina
      • Principal Investigator: Diane Kamen
      • Contact: Stephanie Dezzutti; Phone Number: 843-792-8997; Email: brays@musc.edu
      • Contact: Lori Ann Ueberroth; Phone Number: 843-792-1964; Email: ueberro@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 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.

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

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 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.	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 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.	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	Complete renal response is defined as all of the following: Urine protein-to-creatinine ratio (UPCR) <= 0.5, based on a 24-hour urine collection; 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; 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	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	Complete renal response is defined as all of the following: Urine protein-to-creatinine ratio (UPCR) <= 0.5, based on a 24-hour urine collection; 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; 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	Overall renal response is defined as all of the following: >= 50 percent improvement in the urine protein-to-creatinine ratio (UPCR) compared to baseline, based on a 24-hour urine collection; 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; Prednisone <= 5 mg/day from Week 8, according to the prednisone dosing restrictions	Weeks 12, 24, 36, 48 and 60
Proportion of participants who experience renal treatment failures	Renal treatment failure is defined as any one of the following: Worsening proteinuria, defined as both of the following:Urine protein-to-creatinine ratio (UPCR) > 1.0>= 50 percent increase in UPCR compared to the lowest previous value; Progressive deterioration in renal function, defined as both of the following:Serum creatinine >1.5>= 50 percent increase in serum creatinine compared to the lowest previous value; Nephritis that worsens or fails to sufficiently improve, according to the judgment of the investigator; Receipt of a prohibited immunosuppressive medication, including but not limited to cyclophosphamide, azathioprine, solumedrol, rituximab, belimumab, and calcineurin inhibitors	Week 0 to Week 60
Change in Serum IgM over study participation	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)	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)	BLISS-LN primary efficacy renal response (PERR) defined as all of the following: UPCR ≤ 0.7, and; eGFR ≥ 60 ml/min/1.73m2, or if < 60 ml/min/1.73m2, then ≥ 80% of the eGFR at baseline, and; no receipt of a prohibited immunosuppressive or immunomodulatory medication	Weeks 12, 24, 36, 48, and 60
Anti-dsDNA antibodies	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	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	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)	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)	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	Adverse Events of Special Interests include: Anaphylaxis; Grade 3 or greater infusion reaction; Grade 3 or greater hypersensitivity reaction; Grade 3 or greater infection; Thromboembolic event	Week 0 to Week 60
Change in Serum IgG over study participation	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

Collaborators and Investigators

• 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

Helpful Links

• Immune Tolerance Network (ITN)

Study record dates

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 (Actual): June 7, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: VIB4920; Lupus Nephritis; Mycophenolate mofetil
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephritis; Lupus Nephritis
• 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