VIBRANT: VIB4920 for Active Lupus Nephritis

• Status: Not yet recruiting
• Trial end date: 2027-03-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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