Clinical trial NCT05201469: VIBRANT: VIB4920 for Active Lupus Nephritis
Official title: A Phase 2a Randomized Placebo-Controlled Double-Blind Multicenter Trial of VIB4920 for Active Lupus Nephritis (ITN091AI)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lupus Nephritis
Keywords: Lupus Nephritis
Mycophenolate mofetil
VIB4920
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2022-01-21
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of participants achieving a complete renal response at week 36
timeFrame: Week 36
Secondary outcomes:
measure: Proportion of participants who achieve a complete renal response
timeFrame: Weeks 12, 24, 48, and 60
measure: Proportion of participants who achieve an overall renal response
timeFrame: Weeks 12, 24, 36, 48 and 60
measure: Proportion of participants who achieve a BLISS-LN primary efficacy renal response (PERR)
timeFrame: Weeks 12, 24, 36, 48, and 60
measure: Urine Protein-to-Creatinine Ratio (UPCR)
timeFrame: Weeks 12, 24, 36, 48, and 60
measure: Anti-dsDNA antibodies
timeFrame: Weeks 12, 24, 36, 48, and 60
measure: Change in proportion of participants with lower C3 levels after treatment initiation
timeFrame: Weeks 12, 24, 36, 48, and 60
measure: Change in proportion of participants with lower C4 levels after treatment initiation
timeFrame: Weeks 12, 24, 36, 48, and 60
measure: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
timeFrame: Weeks 12, 24, 36, 48, and 60
measure: Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus (SLICC/ACR-DI)
timeFrame: Weeks 24 and 60
measure: Proportion of participants who experience renal treatment failures
timeFrame: Week 0 to Week 60
measure: Number of participants who experience at least one serious adverse event
timeFrame: Week 0 to Week 60
measure: Number of participants who experience at least one adverse Events of Special Interest
timeFrame: Week 0 to Week 60
measure: Change in Serum IgM over study participation
timeFrame: Weeks 12, 24, 36, 48, and 60
measure: Change in Serum IgG over study participation
timeFrame: Weeks 12, 24, 36, 48, and 60
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego School of Medicine: Division of Rheumatology, Allergy and Immunology
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center: Division of Rheumatology
state: California
city: Orange
country: United States
facility: University of California, Irvine School of Medicine Division of Rheumatology
state: California
city: San Francisco
country: United States
facility: University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine: Division of Rheumatology
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine: Section of Rheumatology
state: Connecticut
city: Miami
country: United States
facility: University of Miami Miller School of Medicine: Nephrology & Hypertension Division
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine: Division of Rheumatology
state: Georgia
city: Chicago
country: United States
facility: University of Chicago, Department of Medicine: Rheumatology
state: Illinois
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis: Division of Nephrology
state: Missouri
city: Manhasset
country: United States
facility: Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery, New York: Division of Rheumatology
state: New York
city: New York
country: United States
facility: Columbia University Medical Center: Department of Medicine, Division of Rheumatology
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center: Division of Rheumatology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University, Lewis Katz School of Medicine, Department of Medicine: Nephrology
state: Pennsylvania
city: Charleston
country: United States
facility: University of South Carolina
state: South Carolina
Study officials:
affiliation: University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center
name: Maria Dall'Era, M.D.
role: STUDY_CHAIR
affiliation: Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
name: Betty Diamond, M.D.
role: STUDY_CHAIR
affiliation: University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center
name: David Wofsy, M.D.
role: STUDY_CHAIR
References: