Depemokimab for Hypereosinophilic Syndrome

(DESTINY Trial)

Recruiting in Palo Alto (17 mi)

+94 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: GlaxoSmithKline

Must be taking: Standard HES therapy

Must not be taking: Monoclonal antibodies

Disqualifiers: Infections, Cancer, Cardiovascular disease, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called depemokimab for adults with Hypereosinophilic Syndrome (HES) who are not responding well to their current treatments. The medication aims to lower the number of certain white blood cells that cause symptoms to worsen. Participants will either receive depemokimab or continue their usual treatment.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial allows participants to continue their standard HES therapy while receiving either depemokimab or a placebo.

What data supports the effectiveness of the drug Depemokimab for treating hypereosinophilic syndrome?

Mepolizumab, a drug similar to Depemokimab, has shown effectiveness in reducing disease flares in patients with hypereosinophilic syndrome by targeting interleukin-5, a protein involved in the condition. This suggests that Depemokimab, which may work in a similar way, could also be effective. ^{1 2 3 4 5}

How does the drug Depemokimab differ from other treatments for hypereosinophilic syndrome?

Depemokimab is unique because it is a monoclonal antibody that targets specific proteins involved in the immune response, potentially offering a more targeted approach compared to traditional treatments like corticosteroids, which have broader effects. This specificity may lead to fewer side effects and improved outcomes for patients with hypereosinophilic syndrome. ^{2 5 6 7 8}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

Adults with Hypereosinophilic Syndrome (HES) who are not pregnant or breastfeeding, weigh at least 40 kg, have had a confirmed HES diagnosis and experienced two or more flares in the past year can join. They must be on stable HES therapy for four weeks before the trial and cannot have certain cancers, heart issues, severe allergies to monoclonal antibodies, or other specific health conditions.

Inclusion Criteria

I am able to understand and sign the consent form.

I have had 2 or more episodes of severe allergic reactions in the last year.

I am not pregnant or breastfeeding and either cannot become pregnant or am using effective birth control.

Exclusion Criteria

My liver is not stable or I have cirrhosis, as assessed by a doctor.

QT interval corrected for heart rate according to Fridericia's formula (QTcF) ≥450 milliseconds (msec) or QTcF ≥480 msec for participants with Bundle Branch Block at Screening Visit 1

You have been treated with oral corticosteroids (OCS) but did not show improvement in symptoms or blood test results according to the doctor's opinion.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive either depemokimab or placebo while continuing their standard of care HES therapy

52 weeks

Regular visits (frequency not specified)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Depemokimab (Monoclonal Antibodies)

Trial Overview The study is testing Depemokimab against a placebo in people with uncontrolled HES over one year. Participants will continue their standard care while being randomly assigned to either receive Depemokimab or a placebo in a 2:1 ratio.

Participant Groups

Group I: Depemokimab Experimental Treatment 1 Intervention

All participants in this arm will receive depemokimab.

Group II: Placebo Placebo Group 1 Intervention

All participants in this arm will receive placebo.

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

Hypereosinophilic syndromes (HES) are characterized by high levels of eosinophils in the blood, leading to organ damage, and can be caused by specific genetic mutations or increased IL-5 production, with a diagnosis requiring exclusion of other conditions.

Imatinib is the first-line treatment for patients with the FIP1L1-PDGFRA fusion gene, while corticosteroids and other agents are used for other variants; recent studies show that mepolizumab can effectively reduce corticosteroid use in F/P-negative patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypereosinophilic syndromes. Roufosse, FE., Goldman, M., Cogan, E.[2018]

In a study of five patients with CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome (L-HES), treatment with JAK inhibitors (ruxolitinib and tofacitinib) resulted in complete clinical remission within three months for all patients, allowing for prednisone withdrawal in four of them.

No adverse events were reported during 3-13 months of follow-up, suggesting that JAK inhibitors may be a safe and effective alternative for patients with L-HES who are unresponsive to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibition for CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome. Faguer, S., Groh, M., Vergez, F., et al.[2023]

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]

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]

Hypereosinophilic syndromes (HES) are rare disorders characterized by high levels of eosinophils that can cause damage to various organs, with treatment options varying based on the underlying cause, including idiopathic, myeloproliferative (M-HES), and lymphocytic (L-HES) variants.

Imatinib has shown remarkable efficacy in patients with the FIP1L1-PDGFRA genetic marker, achieving up to 100% long-term hematological response, while mepolizumab, an IL-5 neutralizing monoclonal antibody, has also shown promise for L-HES, highlighting advancements in targeted therapies for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic and therapeutic management in patients with hypereosinophilic syndromes. Helbig, G., Kyrcz-Krzemień, S.[2022]

A study of 280 patients with hypereosinophilic syndrome (HES) across five European countries revealed that most patients (55%) had idiopathic HES, and common comorbidities included asthma (45%) and anxiety or depression (36%).

Despite extensive treatment with oral corticosteroids (used by 89% of patients), many experienced significant disease burden, with 23% having disease flares and 40% achieving a complete treatment response, indicating a need for more effective targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypereosinophilic syndrome in Europe: Retrospective study of treatment patterns, clinical manifestations, and healthcare resource utilization. Hwee, J., Huynh, L., Du, S., et al.[2023]

Imatinib mesylate was found to induce a durable and complete clinical and biological remission in a 32-year-old man with idiopathic hypereosinophilic syndrome within just 3 weeks, after previous treatments failed.

This treatment appears to be very safe and effective, although the exact mechanism of how it works in this specific syndrome remains unclear, suggesting that other oncogenes may be involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Complete remission with imatinib mesylate (Glivec) of an idiopathic hypereosinophilic syndrome associated with a cutaneous mastocytosis after failure of interferon-alpha]. Pottier, P., Planchon, B., Grossi, O.[2019]

Hypereosinophilic syndromes (HES) are characterized by high eosinophil counts in the blood, which can lead to organ damage due to tissue infiltration, and are often linked to various conditions like allergies, infections, and tumors.

Recent advancements in understanding HES have led to the classification of different subgroups based on molecular profiles, allowing for targeted therapies such as tyrosine kinase inhibitors and monoclonal antibodies to be developed and potentially improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapies for hypereosinophilic disorders: From tyrosine kinase inhibitors to monoclonal antibodies. Towards an increasingly customized management? Iurlo, A., Cattaneo, D.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Hypereosinophilic syndromes. [2018]

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

JAK inhibition for CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome. [2023]

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

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

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

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

5. Poland pubmed.ncbi.nlm.nih.gov

Diagnostic and therapeutic management in patients with hypereosinophilic syndromes. [2022]

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

Hypereosinophilic syndrome in Europe: Retrospective study of treatment patterns, clinical manifestations, and healthcare resource utilization. [2023]

7. France pubmed.ncbi.nlm.nih.gov

[Complete remission with imatinib mesylate (Glivec) of an idiopathic hypereosinophilic syndrome associated with a cutaneous mastocytosis after failure of interferon-alpha]. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Biologic therapies for hypereosinophilic disorders: From tyrosine kinase inhibitors to monoclonal antibodies. Towards an increasingly customized management? [2023]