Belimumab for Pediatric Lupus

(PLUTO Trial)

Recruiting at 28 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must not be taking: Belimumab, B cell therapy

Disqualifiers: Pregnancy, Severe lupus kidney, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

93 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multi-center study to evaluate the safety, pharmacokinetics, and efficacy of belimumab intravenous (IV) in pediatric patients 5 to 17 years of age with active systemic lupus erythematosus

Will I have to stop taking my current medications?

The trial requires that participants are on a stable lupus treatment regimen for at least 30 days before starting the study, so you should not stop taking your current medications if they are part of this regimen.

What data supports the effectiveness of the drug Belimumab for treating pediatric lupus?

Belimumab has been shown to reduce disease activity in adults with systemic lupus erythematosus (SLE) and is now approved for children aged 5 to 17 with SLE. Clinical trials have demonstrated its ability to lower B-cell levels, which are involved in the disease, and improve symptoms in both adults and children. ^{1 2 3 4 5}

Is Belimumab safe for use in humans?

Belimumab (also known as Benlysta) has been approved by the FDA for use in both adults and children with systemic lupus erythematosus (SLE), and studies have highlighted its safety profile. It has been evaluated in clinical trials for both adults and children, showing that it is generally safe when used as part of standard therapy for SLE. ^{1 2 3 6 7}

What makes the drug Belimumab unique for treating pediatric lupus?

Belimumab is unique because it is the first treatment specifically approved for children with systemic lupus erythematosus (SLE) and works by targeting and inhibiting a protein called B lymphocyte stimulator (BLyS), which plays a role in the immune system's overactivity in lupus. It is administered intravenously and has been shown to help reduce disease activity in children with lupus. ^{1 2 3 8 9}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

This trial is for children aged 5-17 with active systemic lupus erythematosus (SLE), meeting specific criteria. They must have a positive ANA test, an SELENA SLEDAI score ≥ 6, and be on stable SLE treatment for at least 30 days. Girls able to have babies must agree to use birth control. Kids can't join if they've had certain treatments like belimumab or rituximab, recent high-dose steroids or IV cyclophosphamide, severe kidney disease from lupus, major organ transplants, certain infections or diseases not from SLE.

Inclusion Criteria

I, or my child, have agreed to participate and a parent or guardian has given consent.

I am willing to use birth control.

I have been on a steady lupus treatment for at least 30 days.

Exclusion Criteria

Pregnant or nursing

I am scheduled for surgery.

I have not had cancer in the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belimumab or placebo intravenously every 28 days for 52 weeks

52 weeks

Monthly visits (in-person)

Long-term open label continuation

Participants may continue receiving belimumab in an open-label setting

5-10 years

Long-term safety follow-up

Participants are monitored for long-term safety outcomes

5-10 years

Treatment Details

Interventions

• Belimumab

Trial Overview The study tests the safety and effectiveness of belimumab (an intravenous medication) in kids with lupus compared to a placebo. Belimumab will be given alongside standard therapies that participants are already using for their condition.

Participant Groups

Group I: Arm 1 Experimental Treatment 1 Intervention

belimumab 10mg/kg IV monthly

Group II: Arm 2 Placebo Group 1 Intervention

Normal Saline IV monthly

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?

GlaxoSmithKline

Lead 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

Human Genome Sciences Inc., a GSK Company

Industry Sponsor

Trials

14

Recruited

3,600+

Findings from Research

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]

In a study of 17 female patients with lupus nephritis treated with belimumab for a median of 36 months, all patients experienced resolution of arthralgia and skin manifestations, indicating its efficacy in managing these symptoms.

Belimumab treatment led to normalization of proteinuria in three patients and allowed for the reduction or complete withdrawal of corticosteroids in 35% of patients, demonstrating its potential to improve kidney function and reduce reliance on steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient). Binda, V., Trezzi, B., Del Papa, N., et al.[2021]

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 (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 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]

Benlysta (belimumab) is the first new drug approved for systemic lupus erythematosus (SLE) in 50 years, providing a new treatment option for patients with this complex disease.

Clinical trials suggest that Benlysta is effective in reducing SLE activity and flares in patients who are antinuclear antibody-positive, potentially allowing for lower doses of background medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab and the clinical data. Shum, K., Askanase, A.[2021]

Belimumab (Benlysta®) was approved by the US FDA in March 2011, marking the first new treatment for lupus in over 50 years, despite its modest efficacy.

Dr. Tsokos highlighted that while belimumab's clinical trial design was innovative and necessary for its approval, future lupus trials may need to address challenges in patient selection and trial endpoints to improve efficacy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab efficacy is 'mild' but market potential still great†: anticipating us approval of the first lupus drug since 1957. Weintraub, B.[2016]

References

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

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

2. Italy pubmed.ncbi.nlm.nih.gov

Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient). [2021]

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

Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison. [2021]

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

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

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

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

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

Belimumab and the clinical data. [2021]

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

Belimumab efficacy is 'mild' but market potential still great†: anticipating us approval of the first lupus drug since 1957. [2016]

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

Prediction of Belimumab Pharmacokinetics in Chinese Pediatric Patients with Systemic Lupus Erythematosus. [2022]