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

Trial Summary

What is the purpose of this trial?

This two year study will evaluate the effects of giving belimumab (Benlysta) to patients with Early Lupus. Early lupus is a diagnosis of lupus within 2 years. Subjects will be randomized to receive belimumab or placebo during the first year. During the second year, subjects who were randomized to belimumab will be rerandomized to continue to receive belimumab or to receive placebo. The study will look at clinical effects as well as effects on the immune system.

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 data supports the effectiveness of the drug Belimumab for treating early lupus?

Research shows that Belimumab, a drug used for systemic lupus erythematosus (SLE), helps reduce disease activity and flares, improves quality of life, and is generally well tolerated. It works by targeting and inhibiting a protein that helps B cells (a type of immune cell) survive and multiply, which is beneficial for patients with active lupus. ^{1 2 3 4 5}

Is belimumab safe for humans?

Belimumab has been studied for safety in patients with systemic lupus erythematosus (SLE), and it is generally considered safe when used with standard therapy. It has been approved for use in adults and children with SLE, and its safety profile has been evaluated in clinical trials and real-world use. ^{1 2 6 7 8}

What makes the drug Belimumab unique for treating lupus?

Belimumab is unique because it is the only biological drug approved specifically for treating non-renal systemic lupus erythematosus (SLE) by targeting and inhibiting a protein that helps B cells survive and multiply, which are involved in the disease. It can be administered either intravenously or subcutaneously, offering flexibility in treatment. ^{2 3 4 7 8}

Research Team

Cynthia Aranow, M.D.

Principal Investigator

Feinstein Institute for Medical Research, Northwell Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

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

Post-marketing experiences with belimumab in the treatment of SLE patients. [2015]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Belimumab: A Review in Systemic Lupus Erythematosus. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Belimumab: a guide to its use in systemic lupus erythematosus. [2016]

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

Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. [2022]

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

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Belimumab in systemic lupus erythematosus: a perspective review. [2020]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Management of Pediatric Systemic Lupus Erythematosus: Focus on Belimumab. [2021]