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VIBRANT: VIB4920 for Active Lupus Nephritis (VIBRANT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05201469
Recruitment Status : Recruiting
First Posted : January 21, 2022
Last Update Posted : June 8, 2022
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Lupus Nephritis Drug: VIB4920 Drug: Placebo for VIB4920 Phase 2

Detailed Description:

Up to 114 eligible participants with active lupus nephritis (LN) will receive induction therapy with mycophenolate mofetil (MMF) and methylprednisolone beginning at Week 0.Participants will also receive prednisone 25 mg per day beginning at Week 0 and tapered to 5 mg per day at Week 8.

Participants will be assessed at Week 8 for a renal response. Sixty-six participants with a urine protein-to-creatinine ratio (UPCR) > 0.75 will be randomized 2:1 to receive VIB4920 versus placebo at Week 10. Participants who are not eligible for randomization will complete study participation after the Week 8 study visit, and further care will be provided according to the judgment of the site investigator or treating physician.

Randomized participants will receive VIB4920 1500 mg or placebo intravenously at Weeks 10, 12, 14, 18, 22, 26, 30, and 34, and will continue MMF 2-3 g per day and prednisone 5 mg per day. The primary endpoint will be assessed at Week 38, and participants followed until Week 60.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2a Randomized Placebo-Controlled Double-Blind Multicenter Trial of VIB4920 for Active Lupus Nephritis (ITN091AI)
Actual Study Start Date : May 16, 2022
Estimated Primary Completion Date : August 2026
Estimated Study Completion Date : March 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arm Intervention/treatment
Experimental: VIB4920

Participants will receive VIB4920 1500 mg intravenously at Weeks 10, 12, 14, 18, 22, 26, 30, and 34.

Participants will receive induction therapy with Mycophenolate Mofetil (MMF) beginning at Week 0. The target dose is 2 to 3 g/d and must be reached by Week 4. MMF administration will continue at the target dose through Week 60.

Participants will also receive prednisone 25 mg per day beginning at day 0 or on the day after completion of methylprednisolone

Drug: VIB4920
Participants will receive 1500 mg of VIB4920 at Weeks 10, 12, 14, 18, 22, 26, 30, and 34, while continuing on MMF and prednisone

Placebo Comparator: VIB4920 Placebo

Participants will receive VIB4920 placebo intravenously at Weeks 10, 12, 14, 18, 22, 26, 30, and 34.

Participants will receive induction therapy with MMF beginning at Week 0. The target dose is 2 to 3 g/d and must be reached by Week 4. MMF administration will continue at the target dose through Week 60. Participants will receive a total of 1000 mg of methylprednisolone at Day 0 or Day 1

Participants will also receive prednisone 25 mg per day beginning at day 0 or on the day after completion of methylprednisolone.

Drug: Placebo for VIB4920
Participants will receive placebo for VIB4920 at Weeks 10, 12, 14, 18, 22, 26, 30, and 34, while continuing on MMF and prednisone




Primary Outcome Measures :
  1. Proportion of participants who achieve a complete renal response [ Time Frame: Week 38 ]

    Complete renal response is defined as all of the following:

    1. Urine protein-to-creatinine ratio (UPCR) <= 0.75, 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


Secondary Outcome Measures :
  1. Proportion of participants who achieve a complete renal response [ Time Frame: Weeks 26, 48, and 60 ]

    Complete renal response is defined as all of the following:

    1. Urine protein-to-creatinine ratio (UPCR) <= 0.75, 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

  2. Proportion of participants who achieve an overall renal response [ Time Frame: Weeks 26, 38, 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

  3. Change in proportion of participants who have negative Anti-dsDNA antibodies post treatment initiation [ Time Frame: Weeks 26, 38, 48, and 60 ]
    The change in the proportion of participants who had a negative anti-dsDNA test after initiation of VIB4920 or placebo will be summarized by arm, and will be analyzed using an exact conditional logistic regression model

  4. Change in proportion of participants with lower C3 levels after treatment initiation [ Time Frame: At Weeks 26, 38, 48, and 60 ]
    The change in the proportion of participants who were hypocomplementemic for C3 after initiation of VIB4920 or placebo will be summarized by arm, and analyzed using an exact conditional logistic regression model with the binary response variable for the test result (C3)

  5. Change in proportion of participants with lower C4 levels after treatment initiation [ Time Frame: Weeks 26, 38, 48, and 60 ]
    The change in the proportion of participants who were hypocomplementemic for C4 after initiation of VIB4920 or placebo will be summarized by arm, and analyzed using an exact conditional logistic regression model with the binary response variable for the test result (C4)

  6. Proportion of participants who experience renal treatment failures [ Time Frame: Week 0 to Week 60 ]

    Renal treatment failure is defined as any one of the following:

    1. Worsening proteinuria, defined as both of the following:

      1. Urine protein-to-creatinine ratio (UPCR) > 1.5
      2. >= 50 percent increase in UPCR compared to the lowest previous value
    2. Progressive deterioration in renal function, defined as both of the following:

      1. Serum creatinine >1.5
      2. >= 50 percent increase in serum creatinine compared to the lowest previous value
    3. Nephritis that worsens or fails to sufficiently improve, according to the judgment of the investigator
    4. Receipt of a prohibited immunosuppressive medication, including but not limited to cyclophosphamide, azathioprine, solumedrol, rituximab, belimumab, and calcineurin inhibitors

  7. Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) post treatment [ Time Frame: Weeks 26, 38, 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 with the SLEDAI-2K score at the timepoint as the dependent variable

  8. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus (SLICC/ACR-DI) post treatment [ Time Frame: Weeks 26 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 with the SLICC/ACR-DI score at the time point as the dependent variable

  9. 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.

  10. Number of participants who experience at least one adverse event of special interest [ Time Frame: Week 0 to Week 60 ]

    Adverse events of special interest 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

  11. Change in Serum IgM over study participation [ Time Frame: Weeks 26, 38, 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

  12. Changes in Serum IgG over study participation [ Time Frame: Weeks 26, 38, 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Classification of Systemic Lupus Erythematosus (SLE) by any of the following criteria:

    1. the 1997 update of the 1982 American College of Rheumatology (ACR) criteria
    2. or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria
    3. or the 2019 European League Against Rheumatism (EULAR)/ACR criteria
  2. 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
  3. Renal biopsy documentation at 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:

  1. Inability or unwillingness to give written informed consent or comply with study protocol
  2. 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
  3. Treatment with a biologic agent 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. End stage renal disease, defined as Estimated glomerular filtration rate (eGFR) < 20 ml/min/1.73m^2
  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.
    5. 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

  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/mcl
    2. Neutropenia (absolute neutrophil count < 1000/mm^3)
    3. Anemia (hemoglobin < 8 g/dL)
    4. Thrombocytopenia (platelets < 50,000/mm^3)
    5. Aspartate aminotransferase 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 child- bearing 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05201469


Locations
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United States, California
University of California San Diego School of Medicine: Division of Rheumatology, Allergy and Immunology Not yet recruiting
La Jolla, California, United States, 92093
UCLA Medical Center: Division of Rheumatology Not yet recruiting
Los Angeles, California, United States, 90095
University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center Not yet recruiting
San Francisco, California, United States, 94143
United States, Colorado
University of Colorado School of Medicine: Division of Rheumatology Not yet recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School of Medicine: Section of Rheumatology Not yet recruiting
New Haven, Connecticut, United States, 06519
United States, Florida
University of Miami Miller School of Medicine: Nephrology & Hypertension Division Not yet recruiting
Miami, Florida, United States, 33136
United States, Georgia
Emory University School of Medicine: Division of Rheumatology Not yet recruiting
Atlanta, Georgia, United States, 30307
United States, Illinois
University of Chicago, Department of Medicine: Rheumatology Not yet recruiting
Chicago, Illinois, United States, 60637
United States, Minnesota
University of Minnesota Medical School: Division of Renal Diseases and Hypertension Not yet recruiting
Duluth, Minnesota, United States, 55805
United States, Missouri
Washington University School of Medicine in St. Louis: Division of Nephrology Not yet recruiting
Saint Louis, Missouri, United States, 63110
Washington University School of Medicine in St. Louis: Division of Rheumatology Not yet recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases Recruiting
Manhasset, New York, United States, 11030
Contact: Julia Weiner    212-342-1587    jkw2160@cumc.columbia.edu   
Principal Investigator: Cynthia Aranow         
Hospital for Special Surgery, New York: Division of Rheumatology Not yet recruiting
New York, New York, United States, 10021
Columbia University Medical Center: Department of Medicine, Division of Rheumatology Not yet recruiting
New York, New York, United States, 10032
United States, Pennsylvania
Temple University, Lewis Katz School of Medicine, Department of Medicine: Nephrology Not yet recruiting
Philadelphia, Pennsylvania, United States, 19140
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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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
Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT05201469    
Other Study ID Numbers: DAIT ITN091AI
First Posted: January 21, 2022    Key Record Dates
Last Update Posted: June 8, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical mechanistic data from NIAID/DAIT-funded grants and contracts
Time Frame: Within 24 months after database lock for the trial
Access Criteria: Open Access
URL: http://www.immport.org/home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Lupus Nephritis
Mycophenolate mofetil
VIB4920
Additional relevant MeSH terms:
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Nephritis
Lupus Nephritis
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases