VIB4920 for Lupus Nephritis

(VIBRANT Trial)

Recruiting at 18 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

Must be taking: Mycophenolate, Prednisone

Must not be taking: Biologics, Rituximab

Disqualifiers: Malignancy, End stage renal, Transplant, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

74 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called VIB4920, along with two other medications, MMF and prednisone, to treat kidney problems caused by lupus. The study involves people who have active lupus nephritis, a serious kidney condition. The treatment aims to reduce inflammation and calm the immune system to help improve kidney function. MMF has been established as an effective treatment for lupus nephritis, often used in combination with other medications like prednisone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have been treated with certain biologic agents or investigational drugs recently, and you must be able to take mycophenolate mofetil and prednisone.

What makes the drug VIB4920 unique for treating lupus nephritis?

VIB4920, also known as Dazodalibep, is unique because it is being studied specifically for lupus nephritis, a condition with limited treatment options, and it may offer a novel approach compared to existing therapies like intravenous immunoglobulin or belimumab, which target different pathways in the immune system. ^{1 2 3 4 5}

Research Team

Maria Dall'Era, M.D.

Principal Investigator

University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center

Betty Diamond, M.D.

Principal Investigator

Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases

David Wofsy, M.D.

Principal Investigator

University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center

Eligibility Criteria

This trial is for adults over 18 with active lupus nephritis, diagnosed by specific criteria and a recent kidney biopsy. Participants must have had a COVID-19 vaccine as per CDC guidelines. Those with substance abuse history, certain infections like HIV or tuberculosis, past significant infections, or on treatments like biologics (except belimumab) are excluded.

Inclusion Criteria

I have been diagnosed with Systemic Lupus Erythematosus.

You had a kidney biopsy within the last 24 weeks and it showed specific criteria.

Your UPCR (urine protein-to-creatinine ratio) is higher than 1.0 based on a 24-hour urine collection before the study starts.

Exclusion Criteria

I am unwilling to use birth control.

I have previously been treated with VIB4920.

I haven't taken any biologic treatment recently, except for belimumab.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VIB4920 or placebo intravenously at Weeks 0, 2, 4, 8, 12, 16, 20, and 24, along with methylprednisolone, MMF, and prednisone

24 weeks

8 visits (in-person)

Primary Endpoint Assessment

Assessment of primary endpoint, complete renal response, at Week 36

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment until Week 60

24 weeks

Treatment Details

Interventions

• Placebo for VIB4920
• VIB4920

Trial Overview The VIBRANT study tests the effectiveness of VIB4920 combined with mycophenolate mofetil (MMF) and prednisone in treating lupus nephritis compared to a placebo. This double-blind study means neither participants nor researchers know who's receiving the real treatment versus the placebo.

Participant Groups

Group I: VIB4920 Experimental Treatment 1 Intervention

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.

Group II: VIB4920 Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Findings from Research

In a study of seven patients with treatment-resistant membranous and membranoproliferative lupus nephritis, all patients showed a beneficial response to high-dose intravenous immunoglobulin (IVIg) therapy, indicating its potential efficacy for this condition.

Patients experienced significant reductions in proteinuria and improvements in plasma albumin levels after IVIg treatment, suggesting that IVIg may help manage kidney-related symptoms in lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin treatment of lupus nephritis. Levy, Y., Sherer, Y., George, J., et al.[2022]

In the phase 3 BLISS-LN study involving 448 patients with lupus nephritis, belimumab significantly improved kidney-related outcomes compared to placebo, with a higher percentage of patients achieving primary and complete renal responses, especially in relapsed patients.

The efficacy of belimumab was consistent regardless of whether patients received glucocorticoid pulses during induction therapy, indicating its potential as a reliable treatment option for both newly diagnosed and relapsed lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of belimumab on kidney-related outcomes in patients with lupus nephritis: post hoc subgroup analyses of the phase 3 BLISS-LN trial. Anders, HJ., Furie, R., Malvar, A., et al.[2023]

In a Phase 2b clinical trial involving 547 patients with systemic lupus erythematosus (SLE), the highest dose of blisibimod (200 mg once-weekly) showed statistically significant improvements in disease response rates compared to placebo, particularly in patients with severe disease.

Blisibimod was found to be safe, with no significant differences in serious adverse events or infections compared to placebo, indicating it could be a viable treatment option for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study. Furie, RA., Leon, G., Thomas, M., et al.[2022]

The Fc gamma RIIIA-V/F158 polymorphism is associated with an increased risk of developing lupus nephritis, as shown by a meta-analysis of 11 studies involving 1154 patients with lupus nephritis and 1261 SLE patients without nephritis.

Patients with the low-binding F158 allele, particularly FF homozygotes, have a significantly higher risk of renal disease compared to those with the VV homozygous genotype, indicating the polymorphism's role in modulating disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Fc gamma RIIIA-F158 allele is a risk factor for the development of lupus nephritis: a meta-analysis. Karassa, FB., Trikalinos, TA., Ioannidis, JP.[2004]

In a phase II study involving 147 patients with active lupus nephritis, the primary endpoint of improved urine protein-creatinine ratio was not met for anifrolumab compared to placebo, indicating limited efficacy in this measure.

However, the intensified regimen of anifrolumab showed numerical improvements in secondary outcomes, such as complete renal response and sustained glucocorticoid reductions, although there was a higher incidence of herpes zoster in the anifrolumab groups compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Jayne, D., Rovin, B., Mysler, EF., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin treatment of lupus nephritis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Effect of belimumab on kidney-related outcomes in patients with lupus nephritis: post hoc subgroup analyses of the phase 3 BLISS-LN trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The Fc gamma RIIIA-F158 allele is a risk factor for the development of lupus nephritis: a meta-analysis. [2004]

5. England pubmed.ncbi.nlm.nih.gov

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. [2022]