Belimumab for Early Lupus

Overseen By Cynthia Aranow, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Northwell Health

Must be taking: Hydroxychloroquine

Must not be taking: Biologics, Azathioprine, Mycophenolate, others

Disqualifiers: Renal disease, HIV, Hepatitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how belimumab affects individuals diagnosed with lupus within the last two years. Lupus is an autoimmune disease in which the immune system attacks the body. Participants will receive either belimumab or a placebo to assess the medication's impact on the condition and the immune system over two years. Suitable candidates have had mild to moderate lupus for less than two years and have not tried certain lupus medications. As a Phase 4 trial, belimumab is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires a stable dose of corticosteroids and methotrexate if you are on them. You must also be on hydroxychloroquine unless you cannot tolerate it.

What is the safety track record for belimumab?

Research has shown that belimumab is generally safe for patients. Studies have found that it does not cause serious harm. In adults with systemic lupus erythematosus (SLE), belimumab was safe to use for up to seven years. Serious side effects are rare, and most people tolerate the treatment well. These findings suggest that belimumab is a safe option for treating lupus, even for those who are newly diagnosed. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Belimumab is unique because it specifically targets and inhibits a protein called BLyS, which plays a crucial role in the survival of B cells that are overactive in lupus. Most treatments for lupus work by broadly suppressing the immune system, but belimumab offers a more targeted approach, potentially reducing side effects associated with widespread immune suppression. Researchers are excited about belimumab because it can be administered subcutaneously, making it more convenient for patients who prefer self-administration at home compared to the conventional intravenous treatments. Additionally, the excitement also stems from belimumab's potential to significantly improve the long-term management of early lupus by directly addressing the underlying autoimmune activity.

What is the effectiveness track record for belimumab in treating early lupus?

Research has shown that belimumab effectively treats systemic lupus erythematosus (SLE), which resembles early lupus. Studies have found that patients taking belimumab experience significant improvements, such as fewer SLE symptoms. For instance, many patients on belimumab showed a noticeable drop in disease activity. Additionally, a large number of patients could reduce or stop using steroids after some time on belimumab. In this trial, participants will be assigned to different arms: some will receive belimumab alone, some will receive belimumab followed by a placebo, and others will receive a placebo throughout. These findings suggest that belimumab can help people with early lupus manage their symptoms effectively. ^{2 6 7 8 9}

Who Is on the Research Team?

Cynthia Aranow, M.D.

Principal Investigator

Feinstein Institute for Medical Research, Northwell Health

Are You a Good Fit for This Trial?

This trial is for individuals diagnosed with early lupus (within the last 2 years), who have mild to moderate disease activity. Participants must be ANA and anti-ds DNA antibody positive, on stable medication doses, able to consent, and use birth control if of reproductive potential. Exclusions include severe organ dysfunction, certain infections or immunodeficiencies, recent drug abuse, pregnancy/lactation, psychiatric disorders affecting participation.

Inclusion Criteria

Mild to moderate disease activity defined by a SLEDAI-2K ≥4

I agree to use birth control during and for 4 months after treatment.

I have been diagnosed with lupus according to ACR criteria.

Exclusion Criteria

I have taken drugs like azathioprine or cyclophosphamide before.

Hemoglobin: < 8.0 gm/dL

I have been treated with medications like rituximab or belimumab for lupus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Year 1

Participants receive subcutaneous belimumab or placebo weekly for 1 year

52 weeks

Treatment Year 2

Participants previously on belimumab are rerandomized to continue belimumab or switch to placebo for another year

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belimumab
• Belimumab/Placebo
• Placebo

Trial Overview The study tests Belimumab's effects on patients with early lupus over two years. In year one, participants are randomly assigned to receive either Belimumab or a placebo. In the second year, those initially given Belimumab may continue it or switch to a placebo. The focus is on clinical outcomes and immune system responses.

How Is the Trial Designed?

Group I: Belimumab/Placebo Experimental Treatment 1 Intervention

Subjects in this arm will receive 200mg belimumab for self administration subcutaneously weekly for 1 year and then placebo injections subcutaneously for 1 year.

Group II: Belimumab Active Control 1 Intervention

Subjects in this arm will receive 200mg belimumab for self administration subcutaneously weekly for 2 years

Group III: Placebo Placebo Group 1 Intervention

Subjects in this arm will receive placebo for self administration subcutaneously weekly for 2 years

Belimumab is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Benlysta for:

• Systemic lupus erythematosus (SLE)

Approved in European Union as Benlysta for:

• Systemic lupus erythematosus (SLE)

Approved in Canada as Benlysta for:

• Systemic lupus erythematosus (SLE)

Approved in Japan as Benlysta for:

• Systemic lupus erythematosus (SLE)

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a study involving 364 patients with systemic lupus erythematosus (SLE), long-term treatment with belimumab combined with standard therapy demonstrated a stable or declining incidence of adverse events over 4 years, indicating a favorable safety profile.

The most common side effects were mild, such as arthralgia and upper respiratory infections, and serious infusion reactions were rare, suggesting that belimumab can be safely administered for extended periods in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. Merrill, JT., Ginzler, EM., Wallace, DJ., et al.[2013]

In a phase III trial with 819 patients, belimumab at 10 mg/kg significantly improved the SLE Responder Index response rate at week 52 compared to placebo (43.2% vs. 33.5%), indicating its efficacy in reducing disease activity in systemic lupus erythematosus (SLE).

Belimumab was generally well tolerated, with serious adverse events being comparable across treatment groups, suggesting that it is a safe addition to standard therapy for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Furie, R., Petri, M., Zamani, O., et al.[2022]

Belimumab (Benlysta®) is an effective treatment for adults with active, autoantibody-positive systemic lupus erythematosus (SLE), particularly for those who have high disease activity despite standard therapy.

In multinational trials, patients receiving belimumab showed significantly higher rates of achieving an SLE Responder Index response at 52 weeks compared to those receiving a placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab: a guide to its use in systemic lupus erythematosus. Scott, LJ., Burness, CB., McCormack, PL.[2016]

Belimumab is a monoclonal antibody that effectively targets and inhibits B-cell activating factor, leading to reduced B-cell levels and improved disease activity in patients with active systemic lupus erythematosus (SLE).

Clinical trials and post-marketing data indicate that belimumab is beneficial for lupus patients who continue to experience active disease despite receiving standard of care therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing experiences with belimumab in the treatment of SLE patients. Askanase, AD., Yazdany, J., Molta, CT.[2015]

Belimumab is an effective treatment for autoantibody-positive systemic lupus erythematosus (SLE) in adults, as demonstrated in phase III trials and real-world studies, showing its ability to inhibit B-lymphocyte stimulator.

The safety profile of belimumab is favorable, and there is ongoing research into its use for childhood-onset SLE and other specific SLE disease states, indicating its potential for broader applications in lupus treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab in systemic lupus erythematosus: a perspective review. Hui-Yuen, JS., Li, XQ., Askanase, AD.[2020]

In patients with autoantibody-positive systemic lupus erythematosus (SLE), treatment with the BLyS-specific inhibitor belimumab led to significant reductions in immunoglobulin G (IgG) and autoantibody levels, as well as improvements in complement levels, indicating a positive effect on disease activity.

Belimumab treatment resulted in decreased numbers of naive and activated B cells, while not affecting memory B cells or T cell populations, suggesting a targeted mechanism of action that may help normalize immune function in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Stohl, W., Hiepe, F., Latinis, KM., et al.[2022]

Belimumab is an effective treatment for autoantibody-positive systemic lupus erythematosus (SLE) in both adults and children aged 5 to 17, as supported by phase III trials in adults and a phase II trial in children.

The drug works by inhibiting B lymphocyte stimulator (BLyS), which is crucial for B cell activation, and has a favorable safety profile, making it a promising option for managing moderate disease activity in SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Pediatric Systemic Lupus Erythematosus: Focus on Belimumab. Guzman, M., Hui-Yuen, JS.[2021]

Belimumab is an effective add-on therapy for adults with active, autoantibody-positive systemic lupus erythematosus (SLE), showing significant reductions in disease activity and flare severity in phase III trials.

The treatment is generally well tolerated, has low rates of immunogenicity, and offers benefits such as steroid-sparing effects and improved quality of life, making it a convenient option for long-term management of SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab: A Review in Systemic Lupus Erythematosus. Blair, HA., Duggan, ST.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9314515/

Real-World Effectiveness of Belimumab in Systemic Lupus ... This study reports a systematic review and meta-analysis of the literature to evaluate the real-world effectiveness of belimumab for the treatment of SLE.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0011393X24000080

Usefulness of Belimumab in Adult Patients With Systemic ... Significantly more belimumab-treated patients achieved a ≥4-point reduction in SLEDAI (relative risk 1.28; 95% confidence interval, 1.16–1.40; P < 0.00001) ...

3. benlystahcp.com benlystahcp.com/lupus/efficacy/

Efficacy for Lupus | BENLYSTA (belimumab) for HCPs Real-world data. 86%. of patients reduced or discontinued steroids at Week 264,5. Real-world, observational cohort study, results are descriptive.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01729455

Study Details | NCT01729455 | Safety and Effectiveness of ... Safety and Effectiveness of BENLYSTA (Belimumab) in Systemic Lupus Erythematosus (SLE) Registry (SABLE). ClinicalTrials.gov ID NCT01729455.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11340010/

Belimumab in early systemic lupus erythematosus The BLISS‐LN study assessed the efficacy of belimumab on LN and demonstrated significant improvements in outcomes. In addition, a previous observational ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3389390/

Efficacy and Safety Data of Belimumab in Patients with ... Treatment with belimumab is well tolerated and has not been associated with significant toxicity. Keywords: lupus, BLyS, BAFF, belimumab, autoantibodies, B- ...

7. ard.bmj.com ard.bmj.com/content/83/Suppl_1/1837.1

BeEARLY, A PHASE 4, PROSPECTIVE, OPEN-LABEL ... This clinical open-label trial will investigate the efficacy and safety of subcutaneous BEL in adults with early, active SLE, using relevant disease activity ...

8. jrheum.org jrheum.org/content/41/2/300

Disease Control and Safety of Belimumab Plus Standard ... Disease control and safety profile were maintained in patients with active SLE taking belimumab plus standard therapy for up to 7 years.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9679798/

Safety of belimumab in adult patients with systemic lupus ... This evidence continues to support a positive benefit–risk profile of belimumab in the treatment of adult patients with SLE.