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VIBRANT: VIB4920 for Active Lupus Nephritis (VIBRANT)

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ClinicalTrials.gov Identifier: NCT05201469
Recruitment Status : Recruiting
First Posted : January 21, 2022
Last Update Posted : June 7, 2024
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE January 7, 2022
First Posted Date  ICMJE January 21, 2022
Last Update Posted Date June 7, 2024
Actual Study Start Date  ICMJE May 16, 2022
Estimated Primary Completion Date August 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2024)
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
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2022)
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2024)
  • 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
  • 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
  • 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
  • Urine Protein-to-Creatinine Ratio (UPCR) [ Time Frame: Weeks 12, 24, 36, 48, and 60 ]
    Based on 24-hour urine collection
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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) > 1.0
      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
  • 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.
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2022)
  • 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
  • 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
  • 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
  • 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)
  • 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)
  • 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
  • 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
  • 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
  • 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.
  • 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
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE VIBRANT: VIB4920 for Active Lupus Nephritis
Official Title  ICMJE A Phase 2a Randomized Placebo-Controlled Double-Blind Multicenter Trial of VIB4920 for Active Lupus Nephritis (ITN091AI)
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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Lupus Nephritis
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.

    Intervention: Drug: VIB4920
  • 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.

    Intervention: Drug: Placebo for VIB4920
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 13, 2023)
74
Original Estimated Enrollment  ICMJE
 (submitted: January 7, 2022)
114
Estimated Study Completion Date  ICMJE March 2027
Estimated Primary Completion Date August 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05201469
Other Study ID Numbers  ICMJE DAIT ITN091AI
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Current Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Original Responsible Party Same as current
Current Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date June 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP