CLINICAL TRIAL / NCT05201469
VIBRANT: VIB4920 for Active Lupus Nephritis
- Interventional
- Active
- NCT05201469
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).
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.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
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.