Mepolizumab for Hypereosinophilic Syndrome

(SPHERE Trial)

Recruiting at 18 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must be taking: HES therapy

Must not be taking: Monoclonal antibodies

Disqualifiers: Life-threatening HES, EGPA, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to investigate the efficacy and safety of mepolizumab in children and adolescents with hypereosinophilic syndrome (HES) who are receiving standard of care (SoC) therapy.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of their current HES therapy for at least 4 weeks before starting the study medication. This means you should not stop taking your current medications if they are part of your HES treatment.

What data supports the effectiveness of the drug Mepolizumab for Hypereosinophilic Syndrome?

Mepolizumab has been shown to improve quality of life and reduce activity impairments in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), suggesting it may have beneficial effects in conditions involving eosinophils, like Hypereosinophilic Syndrome. ^{1 2 3 4 5}

Is mepolizumab safe for humans?

Mepolizumab has been studied for safety in people with conditions like hypereosinophilic syndrome and severe eosinophilic asthma. These studies generally show that it is safe for human use, with some treatment-related side effects reported. ^{6 7 8 9 10}

How is the drug Mepolizumab unique for treating hypereosinophilic syndrome?

Mepolizumab is unique for treating hypereosinophilic syndrome because it specifically targets and reduces disease flares in patients with this condition, especially those who have had multiple flares in the past year. It works by inhibiting interleukin-5 (IL-5), a protein that plays a key role in the growth and survival of eosinophils, which are a type of white blood cell involved in this syndrome. ^{1 2 11 12 13}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

Children and teens aged 6-17 with hypereosinophilic syndrome (HES) for at least 6 months, having a high eosinophil count, stable on current HES therapy, and who've had two or more HES flares in the past year can join. Those with certain infections, cancer history within a year, non-responsive to steroids, prior mepolizumab use or other monoclonal antibodies recently cannot participate.

Inclusion Criteria

Signed written informed consent

I am either male or female.

I have been diagnosed with HES for at least 6 months.

Exclusion Criteria

I have not had serious infections or been on infection treatment in the last 4 weeks.

Participants with documented history of any clinically significant cardiac damage prior to Screening (Visit 1) that, in the opinion of the investigator, would impact the participant's participation during the study

My previous cancer has been in remission for less than a year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mepolizumab in addition to standard of care therapy

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Mepolizumab

Trial Overview The trial is testing the effectiveness and safety of mepolizumab when added to standard care for young patients with HES. It aims to see if this treatment helps reduce symptoms and manage the condition better than standard treatments alone.

Participant Groups

Group I: Participants receiving mepolizumab Experimental Treatment 1 Intervention

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

Findings from Research

In a study of 10 prednisone-dependent asthma patients, weight-adjusted intravenous reslizumab significantly reduced sputum eosinophils by 91.2% and blood eosinophils by 87.4%, showing a strong efficacy compared to placebo.

Reslizumab also led to greater improvements in lung function (FEV1) and asthma control compared to the previously used mepolizumab, indicating it may be a more effective treatment option for managing eosinophilia in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight-adjusted Intravenous Reslizumab in Severe Asthma with Inadequate Response to Fixed-Dose Subcutaneous Mepolizumab. Mukherjee, M., Aleman Paramo, F., Kjarsgaard, M., et al.[2022]

In a 24-week phase III trial involving 549 patients with active rheumatoid arthritis, otilimab did not significantly improve the proportion of patients achieving an ACR20 response compared to placebo, indicating limited efficacy in this population.

While otilimab had a similar safety profile to other treatments, it was less effective than sarilumab, failing to meet the primary endpoint and showing no significant improvements in secondary measures of disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-GM-CSF otilimab versus sarilumab or placebo in patients with rheumatoid arthritis and inadequate response to targeted therapies: a phase III randomised trial (contRAst 3). Taylor, PC., Weinblatt, ME., McInnes, IB., et al.[2023]

Mepolizumab (MEP) significantly reduced relapse rates and therapeutic failures in patients with hypereosinophilic syndrome (HES), showing a 26% reduction with the 300 mg subcutaneous dose and a 48% reduction with the 750 mg intravenous dose, based on a meta-analysis of three randomized controlled trials involving 255 patients.

The treatment also allowed 48% of patients to reduce their prednisone dosage to ≤10 mg/day for at least 8 weeks and achieved eosinophil counts below 600/μL in 51% of patients, with no significant increase in treatment-related adverse effects, indicating its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab in Hypereosinophilic Syndrome: A Systematic Review and Meta-analysis. Alves Júnior, JM., Prota, FE., Villagelin, D., et al.[2022]

Mepolizumab significantly reduced the rate of clinically significant asthma exacerbations in Korean patients with severe eosinophilic asthma, demonstrating its efficacy in this population.

The safety profile of mepolizumab in Korean patients was consistent with that observed in the overall population, indicating it is a safe treatment option for severe eosinophilic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mepolizumab in Korean patients with severe eosinophilic asthma from the DREAM and MENSA studies. Kim, MK., Park, HS., Park, CS., et al.[2021]

In a study of 351 patients with severe eosinophilic asthma, initiating treatment with mepolizumab led to a significant reduction in the use of high-dose inhaled corticosteroids (ICS) over a 12-month period, with 49% of patients reducing or discontinuing ICS.

Patients who discontinued ICS after starting mepolizumab experienced lower rates of chronic oral corticosteroid (OCS) use, fewer exacerbations, and reduced reliance on short-acting β2-agonists, indicating improved clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world study of inhaled corticosteroid use in patients with severe eosinophilic asthma treated with mepolizumab. Corren, J., Silver, J., Molfino, NA., et al.[2022]

Mepolizumab significantly reduced the frequency of disease flares in patients with hypereosinophilic syndrome (HES), showing a reduction in flare rates by 58% to 84% across different baseline blood eosinophil count (BEC) subgroups, indicating its efficacy regardless of eosinophil levels.

The treatment was effective even in patients with undetectable baseline serum IL-5 levels, suggesting that low IL-5 should not prevent the use of mepolizumab in HES patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5. Rothenberg, ME., Roufosse, F., Faguer, S., et al.[2022]

A woman successfully treated for psoriasis and psoriatic arthritis with the IL-17 inhibitor secukinumab also managed her severe asthma and nasal polyps with other biologics, demonstrating the potential for concurrent treatment of multiple inflammatory conditions.

The use of secukinumab alongside IL-5 and IL-4 receptor inhibitors highlights the efficacy of targeted biological therapies in managing complex cases of inflammation, suggesting a promising approach for patients with overlapping inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination treatment with monoclonal antibodies: Secukinumab, benralizumab and dupilumab for the combined management of psoriasis and severe asthma. Mahar, PD., Zubrinich, CM., Manuelpillai, N., et al.[2022]

References

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

Weight-adjusted Intravenous Reslizumab in Severe Asthma with Inadequate Response to Fixed-Dose Subcutaneous Mepolizumab. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Mepolizumab improves quality of life and reduces activity impairments in patients with CRSwNP. [2022]

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

Eosinophilic arthritis. [2019]

4. Italy pubmed.ncbi.nlm.nih.gov

Efficacy of tocilizumab therapy in Korean patients with adult-onset Still's disease: a multicentre retrospective study of 22 cases. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Anti-GM-CSF otilimab versus sarilumab or placebo in patients with rheumatoid arthritis and inadequate response to targeted therapies: a phase III randomised trial (contRAst 3). [2023]

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

Mepolizumab in Hypereosinophilic Syndrome: A Systematic Review and Meta-analysis. [2022]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mepolizumab in Korean patients with severe eosinophilic asthma from the DREAM and MENSA studies. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Association Between Baseline Therapy and Flare Reduction in Mepolizumab-Treated Patients With Hypereosinophilic Syndrome. [2022]

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

A real-world study of inhaled corticosteroid use in patients with severe eosinophilic asthma treated with mepolizumab. [2022]

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

Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5. [2022]

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

Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study. [2022]

12. Australia pubmed.ncbi.nlm.nih.gov

Combination treatment with monoclonal antibodies: Secukinumab, benralizumab and dupilumab for the combined management of psoriasis and severe asthma. [2022]

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

Impact of Certolizumab Pegol on Patient-Reported Outcomes in Patients With Axial Spondyloarthritis. [2018]