VIB4920 for Lupus Nephritis

(VIBRANT Trial)

Recruiting at 20 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called VIB4920 for individuals with lupus nephritis, a kidney condition caused by lupus. Researchers aim to determine if VIB4920, combined with two other medications (MMF and prednisone), can improve kidney function. Participants will receive either VIB4920 (also known as HZN-4920, MEDI-4920, or Dazodalibep) or a placebo (inactive substance) through an IV at regular intervals. Ideal candidates for this trial are those diagnosed with active lupus nephritis and experiencing related kidney problems. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in lupus nephritis treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that VIB4920 appears safe and well-tolerated. In a past study involving individuals with rheumatoid arthritis, VIB4920 proved safe and manageable for patients. This suggests it might also be safe for those with lupus nephritis. VIB4920 is undergoing tests for other conditions, such as Sjögren's Syndrome, where it has demonstrated a good safety record. While this information is promising, remember that individual experiences can vary. Always discuss potential risks with the trial team or your doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus nephritis?

Unlike the standard treatments for lupus nephritis, which often involve immunosuppressive drugs like cyclophosphamide or mycophenolate mofetil, VIB4920 is unique because it targets a specific pathway in the immune system. Researchers are excited about VIB4920 as it acts on the CD40-CD40L interaction, which is crucial in the activation of immune responses. By intervening in this pathway, VIB4920 has the potential to provide a more targeted and possibly more effective approach with fewer side effects. This novel mechanism could offer a new hope for patients, potentially improving their quality of life by reducing the burden of the disease.

What evidence suggests that VIB4920 might be an effective treatment for lupus nephritis?

Research shows that VIB4920, which participants in this trial may receive, may help treat autoimmune diseases. Early tests with people who have rheumatoid arthritis found it safe, easy to tolerate, and effective. This suggests it might also help with lupus nephritis, a condition where the immune system attacks the kidneys. VIB4920 targets specific parts of the immune system, potentially reducing the harmful inflammation that damages the kidneys in lupus nephritis. Early results from related studies indicate that it remains effective, with no new safety issues over a 28-week period. These findings offer hope that VIB4920 could benefit people with lupus nephritis. ^{1 2 3 4 6}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 who previously received 1000 mg of methylprednisolone IV within 42 days of Visit 0 will not receive additional methylprednisolone IV on Day 0. Participants who previously received less than 1000 mg of methylprednisolone IV within 42 days of Visit 0 will receive an additional dose of methylprednisolone IV at Day 0, according to the following formula, where X is the intravenous dose previously received and Y is the intravenous dose administered on Day 0: 1000 mg - X = Y. Participants will begin MMF 2-3 g per day and prednisone 25 mg per day, tapered to 5 mg per day by Week 8. The prednisone dose may be tapered more rapidly and to a dose lower than 5 mg/d, at the discretion of the site investigator. Prednisone of no more than 5 mg/d will be continued until Week 60.

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 who previously received 1000 mg of methylprednisolone IV within 42 days of Visit 0 will not receive additional methylprednisolone IV on Day 0. Participants who previously received less than 1000 mg of methylprednisolone IV within 42 days of Visit 0 will receive an additional dose of methylprednisolone IV at Day 0, according to the following formula, where X is the intravenous dose previously received and Y is the intravenous dose administered on Day 0: 1000 mg - X = Y. Participants will begin MMF 2-3 g per day and prednisone 25 mg per day, tapered to 5 mg per day by Week 8. The prednisone dose may be tapered more rapidly and to a dose lower than 5 mg/d, at the discretion of the site investigator. Prednisone of no more than 5 mg/d will be continued until Week 60.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

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 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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05201469

VIBRANT: VIB4920 for Active Lupus Nephritis This is a multi-center double-blind placebo controlled clinical trial evaluating the efficacy of VIB4920 combined with mycophenolate mofetil (MMF) and ...

2. medicine.yale.edu medicine.yale.edu/trial/vibrant-vib4920-for-active-lupus-nephritis-1/

VIBRANT: VIB4920 for Active Lupus Nephritis This is a multi-center double-blind placebo controlled clinical trial evaluating the efficacy of VIB4920 combined with mycophenolate mofetil (

3. immunetolerance.org immunetolerance.org/clinical-trials/vib4920-for-active-lupus-nephritis-vibrant

VIBRANT: VIB4920 for Active Lupus Nephritis VIB4920 was found to be safe, tolerable, and effective in an early phase trial in rheumatoid arthritis patients, and it is currently being used in other trials.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10978744/

Novel and potential future therapeutic options in systemic ... The efficacy was stable, and no new safety concerns were raised during a 28-week, open-label extension study (8). Promising new drug candidates.

5. uclahealth.org uclahealth.org/clinical-trials/vibrant-vib4920-active-lupus-nephritis

VIBRANT: VIB4920 for Active Lupus Nephritis This is a multi-center double-blind placebo controlled clinical trial evaluating the efficacy of VIB4920 combined with mycophenolate mofetil (MMF) and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04129164

NCT04129164 | A Study to Evaluate the Efficacy and ... The purpose of the study is to evaluate the efficacy, safety, and tolerability of VIB4920 (formerly MEDI4920) in adult participants with Sjögren's Syndrome (SS ...