Depemokimab for Hypereosinophilic Syndrome

(DESTINY Trial)

Recruiting at 105 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must be taking: Standard HES therapy

Must not be taking: Monoclonal antibodies

Disqualifiers: Infections, Cancer, Cardiovascular disease, others

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: 1

Duration: 52 weeks

123 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of depemokimab for individuals with hypereosinophilic syndrome (HES), a condition characterized by the buildup of a type of white blood cell that causes problems. The trial aims to determine if depemokimab can reduce flare-ups (sudden worsening of symptoms) in patients who continue to experience issues despite standard treatment. Participants will receive either depemokimab or a placebo (a non-active substance) while maintaining their usual therapy. Suitable candidates have had HES for some time, are on stable treatment, and have experienced at least two flare-ups in the past year. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that depemokimab is promising for treating severe asthma and chronic sinus issues with nasal polyps. In studies involving individuals with severe asthma, depemokimab reduced flare-ups and was generally well-tolerated.

Some participants reported side effects, but these were neither common nor serious, indicating that most did not experience major problems with depemokimab. The FDA is also reviewing the treatment for other conditions, suggesting it has already passed some safety checks.

Overall, the evidence suggests depemokimab is safe for many people, but as with any treatment, experiences can vary. Always consult a doctor about any concerns. ^{1 2 3 4 5}

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

Depemokimab is unique because it targets the root cause of hypereosinophilic syndrome by specifically blocking interleukin-5 (IL-5), a protein that promotes the growth and activity of eosinophils, which are white blood cells involved in this condition. Current treatments, like corticosteroids and other immunosuppressive drugs, often have broad effects and can lead to significant side effects. Depemokimab's targeted approach aims to reduce these side effects while effectively controlling the disease. Researchers are excited about depemokimab because it offers a more precise strategy, potentially leading to better patient outcomes with fewer downsides.

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

Research has shown that depemokimab, which participants in this trial may receive, may help treat conditions with high levels of eosinophils, a type of white blood cell. In studies on severe asthma with elevated eosinophil levels, depemokimab significantly reduced the number of severe flare-ups. This suggests it can help manage diseases caused by eosinophils, such as hypereosinophilic syndrome (HES). Based on these findings, depemokimab could be effective for people with HES who experience frequent flare-ups despite standard treatments. ^{1 2 5 6 7}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Depemokimab

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39248309/

Twice-Yearly Depemokimab in Severe Asthma with an ... Conclusions: Depemokimab reduced the annualized rate of exacerbations among patients with severe asthma with an eosinophilic phenotype. (Funded ...

2. gsk.com gsk.com/media/jeonhvh5/gsk-announces-positive-results-from-phase-iii-severe-asthma-trials-of-depemokimab.pdf

Stock-exchange announcement GSK announces positive results from phase III severe asthma trials of depemokimab. • Primary endpoints met in SWIFT-1 and SWIFT-2 trials ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04719832

Study Details | NCT04719832 | Placebo-controlled Efficacy ... This is a multi-center, randomized, placebo-controlled, double-blind, parallel group study that aims to assess the efficacy and safety of GSK3511294 ...

4. gsk.com gsk.com/en-gb/media/press-releases/depemokimab-late-breaking-data-presented-at-ers-show-a-54-reduction-in-severe-asthma-exacerbations/

Depemokimab late-breaking data presented at ERS show ... Depemokimab is currently being evaluated in phase III trials across a range of other IL-5 mediated diseases, including OCEAN for eosinophilic ...

5. gsk.com gsk.com/en-gb/media/press-releases/gsk-announces-positive-phase-iii-results-from-anchor-trials/

GSK announces positive phase III results from ANCHOR ... GSK today announced positive headline results from the phase III clinical trials ANCHOR-1 and ANCHOR-2, which assessed the efficacy and safety of depemokimab ...

6. gsk.com gsk.com/en-gb/media/press-releases/depemokimab-applications-accepted-for-review-by-the-us-fda/

Depemokimab applications accepted for review by the US ... Depemokimab applications accepted for review by the US FDA for asthma with type 2 inflammation and for chronic rhinosinusitis with nasal polyps ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05281523

NCT05281523 | Efficacy and Safety of Depemokimab ... This study will evaluate the efficacy and safety of depemokimab (GSK3511294) in participants with Chronic rhinosinusitis with nasal polyps (CRSwNP).