Mepolizumab for Hypereosinophilic Syndrome

(SPHERE Trial)

Not currently recruiting at 23 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests mepolizumab to determine its safety and effectiveness for children and teens with hypereosinophilic syndrome (HES), a condition where an excess of white blood cells causes bodily issues. Participants will receive mepolizumab injections alongside their usual treatment to assess improvements. The trial is open to those aged 6 to 17 who have had HES for at least six months and experienced two or more flare-ups in the past year. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that mepolizumab is generally well-tolerated by patients with hypereosinophilic syndrome (HES). In one study, no deaths occurred, and the treatment led to fewer disease flare-ups. Specifically, patients taking mepolizumab had a 66% lower chance of experiencing a flare-up compared to those taking a placebo. Another study found that 57% of patients had a complete response, meaning their symptoms fully improved. Importantly, no new side effects appeared in HES patients beyond those already known from its use in treating severe asthma. This suggests that mepolizumab is relatively safe for managing HES. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about mepolizumab for treating Hypereosinophilic Syndrome (HES) because it offers a targeted approach that differs from existing treatments. Unlike traditional therapies, which often involve corticosteroids or immunosuppressive drugs that broadly dampen the immune system, mepolizumab specifically targets and blocks interleukin-5 (IL-5), a protein that plays a key role in the growth and activation of eosinophils. This targeted action can potentially reduce side effects and improve outcomes by directly addressing the underlying cause of HES. Additionally, mepolizumab is an injectable, which might offer convenience compared to some oral medications.

What evidence suggests that mepolizumab might be an effective treatment for hypereosinophilic syndrome?

Research has shown that mepolizumab effectively treats hypereosinophilic syndrome (HES). Studies found that mepolizumab led to remission in 57.1% to 76.0% of patients. It also significantly reduced blood eosinophil levels, with reductions ranging from 71.4% to 99.1%. Mepolizumab helps reduce disease flare-ups, with 72% of patients experiencing no flares compared to 44% who took a placebo. Overall, these findings suggest that mepolizumab can effectively manage and control HES symptoms. ^{2 3 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1704077/full

Mepolizumab for hypereosinophilic syndrome (HES) Remission rates were 57.1–76.0%. Most studies reported a range of 71.4–99.1% reduction in mean blood eosinophil counts with mepolizumab ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6173586/

Long-Term Clinical Outcomes of High-Dose Mepolizumab ... Data from a multicenter retrospective analysis of treatment responses demonstrated that although 85% of HES patients respond to some dose of GC at 1 month, 40% ...

3. nucalahcp.com nucalahcp.com/hes/efficacy-safety/study-results/

HES Study Results | NUCALA (mepolizumab) for HCPs CLINICAL EFFICACY OF NUCALA ; NUCALA provides proven protection from flares · 72% of patients had zero flares vs 44% with placebo (results are descriptive.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2213219821008916

Safety and Efficacy of Mepolizumab in Hypereosinophilic ... A phase III study demonstrated that compared with placebo, 4-weekly add-on mepolizumab (300 mg subcutaneously) reduced flares in patients with uncontrolled FIP1 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29751154/

Long-Term Clinical Outcomes of High-Dose Mepolizumab ... This study confirms that mepolizumab is an effective and well-tolerated therapy for HES, but suggests that response is more likely in GC-responsive subjects.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34389506/

Safety and Efficacy of Mepolizumab in Hypereosinophilic ... No events were fatal. The annualized flare rate (95% confidence interval) in the previous placebo and previous mepolizumab groups was 0.37 (0.16-0.86) and 0.14 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02836496

NCT02836496 | Efficacy and Safety Study of Mepolizumab ... This study will demonstrate the efficacy of mepolizumab compared with placebo based on maintenance of control of HES symptoms during the treatment period.

8. nucalahcp.com nucalahcp.com/hes/efficacy-safety/safety-profile/

HES Safety Profile | NUCALA (mepolizumab) for HCPs In the 32-week clinical trial in patients with HES (300 mg of NUCALA), no additional adverse reactions were identified to those reported in severe asthma trials ...