Belimumab for Pediatric Lupus

(PLUTO Trial)

Not currently recruiting at 37 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests belimumab, administered through an IV, to determine its safety and effectiveness for children and teens with active lupus, a condition where the immune system attacks healthy body parts. Researchers aim to understand how the body processes the drug and whether it reduces lupus symptoms. Some participants will receive belimumab, while others will receive a placebo (a non-active substance) for comparison. Children and teens aged 5 to 17 with lupus who have stable treatment routines might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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.

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

Research has shown that belimumab is generally safe for children with systemic lupus erythematosus (SLE). In previous studies, children responded to the treatment similarly to adults with the same condition, indicating comparable tolerance. The most common side effects were mild, including nausea, diarrhea, and fever, while serious side effects were rare. Notably, the FDA has already approved belimumab for children with lupus nephritis, a kidney problem related to lupus, which supports its safety. Overall, evidence suggests that belimumab is safe for children with lupus. However, discussing any concerns with a doctor remains important. ^{1 2 3 4 5}

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

Belimumab is unique because it specifically targets and inhibits a protein called B-lymphocyte stimulator (BLyS), which plays a critical role in the survival of B cells that contribute to lupus. Unlike standard treatments for pediatric lupus, such as corticosteroids and immunosuppressants, which broadly suppress the immune system, belimumab offers a more targeted approach. This precision can potentially reduce the harmful side effects associated with conventional therapies, making it an exciting option for researchers and patients alike.

What evidence suggests that belimumab might be an effective treatment for pediatric lupus?

Research has shown that belimumab, which participants in this trial may receive, may help treat lupus in children. Studies found that children taking belimumab were more likely to reach their treatment goals than those taking a placebo. Belimumab lowered disease activity and reduced the risk of severe lupus flare-ups. Real-world data in adults also suggest that belimumab can lead to fewer lupus flares and reduce the need for steroids. This evidence supports the potential effectiveness of belimumab in managing lupus in children. ^{1 3 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

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

Have a historically positive test, or test positive at screening for HIV, Hepatitis B, or Hepatitis C

I am scheduled for surgery.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 (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]

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®) 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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9363663/

Belimumab in childhood systemic lupus erythematosus

Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial.

2.

ard.bmj.com

ard.bmj.com/content/79/10/1340

Safety and efficacy of intravenous belimumab in children ...

At Week 52, compared with placebo, numerically higher proportions of patients receiving belimumab met the primary efficacy endpoint of SLE Responder Index 4 ...

3.

benlystahcp.com

benlystahcp.com/lupus/efficacy-pediatric/

Efficacy for Pediatrics | BENLYSTA (belimumab) for HCPs

BENLYSTA reduced disease activity and the risk of severe flare in pediatric patients with lupus aged 5 years and older.

4.

carragroup.org

carragroup.org/grant/outcomes-of-belimumab-use-for-pediatric-lupus-in-the-childhood-arthritis-and-rheumatology-research-alliance-registry/

Outcomes of Belimumab Use for Pediatric Lupus in the ...

Real-world effectiveness data in adults shows that patients who start belimumab have fewer lupus flares and need lower steroid doses.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11647295/

Efficacy of initial combination with belimumab in newly ...

Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial.

6.

benlystahcp.com

benlystahcp.com/safety/

Safety Profile | BENLYSTA (belimumab) for HCPs

Find the BENLYSTA (belimumab) safety profile for lupus and lupus nephritis, established in clinical trials. Find adverse events and organ damage info.

7.

us.gsk.com

us.gsk.com/en-us/media/press-releases/fda-approves-benlysta-belimumab-autoinjector-for-children-with-active-lupus-nephritis/

FDA approves Benlysta (belimumab) Autoinjector for ...

The 200 mg/mL autoinjector was approved for pediatric patients with active systemic lupus erythematosus (SLE) in 2024. ... safety of Benlysta ...

8.

fda.gov

fda.gov/media/188465/download

NDA/BLA Multi-Disciplinary Review and Evaluation

The safety of belimumab SC in pediatric LN is leveraged from the belimumab's safety ... B lymphocyte stimulator expression in pediatric systemic ...