Depemokimab vs Mepolizumab for Granulomatosis with Polyangiitis

(OCEAN Trial)

Not currently recruiting at 105 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must be taking: Oral corticosteroids

Must not be taking: Omalizumab, Rituximab, Cyclophosphamide, others

Disqualifiers: Cancer, Cardiovascular disease, Immunodeficiency, 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 two treatments, depemokimab and mepolizumab, to determine which is more effective and safer for individuals with eosinophilic granulomatosis with polyangiitis (EGPA). EGPA is a rare disease that causes inflammation in blood vessels and can affect various parts of the body, often accompanied by asthma and high levels of eosinophils, a type of white blood cell. Participants will receive either depemokimab or mepolizumab along with a placebo, allowing researchers to compare the effects of both drugs. This trial suits adults who have had EGPA for at least six months and have experienced flare-ups or resistance to standard treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of oral prednisolone or prednisone and any immunosuppressive therapy (except cyclophosphamide) for at least 4 weeks before starting the study. Some medications, like certain monoclonal antibodies, require a washout period (time without taking them) before joining the trial.

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

Research shows that depemokimab has been tested for safety in treating asthma and chronic sinusitis with nasal polyps. These studies found depemokimab to be safe, with fewer severe asthma attacks, and patients tolerated the treatment well.

For mepolizumab, research has shown it to be safe for patients with inflammatory conditions. The FDA has already approved it for asthma and similar conditions, indicating its general safety for use.

Both treatments in this trial, depemokimab and mepolizumab, are considered safe based on previous research. They have been tested in people before and have shown promising safety results. However, participants should always discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about depemokimab because, unlike current treatments for Granulomatosis with Polyangiitis that focus on general inflammation, depemokimab targets the IL-5 pathway, which plays a crucial role in the disease's progression. This targeted approach could mean more effective management of symptoms with potentially fewer side effects. Additionally, depemokimab may offer a longer duration of action compared to existing options like mepolizumab, potentially reducing the frequency of treatments needed.

What evidence suggests that this trial's treatments could be effective for Granulomatosis with Polyangiitis?

Research has shown that depemokimab, which participants in this trial may receive, can reduce severe asthma attacks by 54%. This suggests its potential usefulness for conditions involving eosinophils, a type of white blood cell that can cause inflammation. Mepolizumab, another treatment option in this trial, has already been approved for treating eosinophilic granulomatosis with polyangiitis (EGPA), where it reduces symptoms and prevents flare-ups. Both treatments target the same inflammation pathway in the body, but depemokimab is newer and might offer additional benefits. These findings suggest that both treatments could be effective for EGPA. ^{2 3 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 relapsing or refractory EGPA who are at least 18 years old, weigh more than 40 kg, and can consent to the study. They must have stable immunosuppressive therapy doses (excluding cyclophosphamide), a non-pregnant/non-breastfeeding status with effective contraception if of childbearing potential, and be on a steady oral steroid dose. Participants should not have severe organ-threatening conditions or recent cancer remission.

Inclusion Criteria

I am able to understand and sign the consent form.

I have been diagnosed with EGPA for at least 6 months and meet the specific criteria.

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

Exclusion Criteria

I am currently being treated for a long-term infection.

My liver tests are within acceptable ranges for the study, and I don't have severe liver or biliary disease.

Your heart's electrical activity, as measured by a test called ECG, is outside the normal range.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either depemokimab or mepolizumab for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Depemokimab
• Mepolizumab

Trial Overview The trial is testing the effectiveness and safety of depemokimab versus mepolizumab in adults with EGPA alongside standard care. It involves comparing these drugs to their respective placebos to see which one better controls the disease symptoms.

How Is the Trial Designed?

Group I: Participants receiving depemokimab+placebo matching mepolizumab Experimental Treatment 2 Interventions

Group II: Participants receiving mepolizumab+placebo matching depemokimab Active Control 2 Interventions

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 (MPZ) demonstrated a 100% retention rate in patients with severe eosinophilic granulomatosis with polyangiitis (EGPA), indicating strong adherence and effectiveness as a remission induction therapy compared to intravenous cyclophosphamide (IVCY), which had a completion rate of only 61.5%.

Patients treated with MPZ experienced fewer adverse events (28.6%) compared to those receiving IVCY (53.8%), and the MPZ group showed a significantly greater reduction in corticosteroid doses after 3 months, suggesting MPZ may be a safer and more effective option for managing EGPA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of mepolizumab therapy in remission induction therapy for eosinophilic granulomatosis with polyangiitis: a retrospective study. Ueno, M., Miyagawa, I., Aritomi, T., et al.[2022]

In a real-world study of 16 patients with relapsing/refractory eosinophilic granulomatosis with polyangiitis (EGPA), mepolizumab (MPZ) showed a 75% remission rate after one year, indicating its effectiveness in managing this condition.

MPZ treatment led to significant reductions in disease activity, as measured by the Birmingham vasculitis activity score (BVAS) and eosinophil counts, while also allowing for a decrease in corticosteroid use, demonstrating its safety and a corticosteroid-sparing effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of mepolizumab in combination with corticosteroids in patients with eosinophilic granulomatosis with polyangiitis. Ueno, M., Miyagawa, I., Nakano, K., et al.[2021]

In the MIRRA study involving 136 patients with eosinophilic granulomatosis with polyangiitis (EGPA), mepolizumab significantly improved remission rates compared to placebo, achieving remission in 54% of patients with a history of ANCA positivity and 27% without, versus 0% and 4% in the placebo group.

Mepolizumab also reduced all types of relapses in patients, demonstrating its efficacy in both patients with and without a vasculitic phenotype, indicating its potential as a beneficial treatment option for EGPA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Benefit of Mepolizumab in Eosinophilic Granulomatosis With Polyangiitis for Patients With and Without a Vasculitic Phenotype. Terrier, B., Jayne, DRW., Hellmich, B., et al.[2023]

In a study of 25 patients with eosinophilic granulomatosis with polyangiitis (EGPA), treatment with mepolizumab significantly reduced the daily dose of oral corticosteroids from an average of 11.04 mg to 3.65 mg, indicating its efficacy in managing the condition.

Mepolizumab also led to significant improvements in asthma control and quality of life scores, with 76% of patients achieving a complete response by the 6th month and 81.25% by the 12th month, demonstrating its potential as a beneficial treatment option for EGPA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Low-Dose Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA): A Real-Life Experience. Özdel Öztürk, B., Yavuz, Z., Aydın, Ö., et al.[2023]

In a phase 2a study involving 159 patients with rheumatoid arthritis, those who received bimekizumab alongside certolizumab pegol showed a significantly greater reduction in disease activity compared to those receiving certolizumab plus placebo, indicating the efficacy of dual IL-17A and IL-17F neutralization.

While the combination treatment was effective, it was associated with a higher incidence of treatment-emergent adverse events, particularly infections, suggesting that while the therapy is promising, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study. Glatt, S., Taylor, PC., McInnes, IB., et al.[2020]

In a study of 27 patients with eosinophilic granulomatosis with polyangiitis (EGPA) treated with mepolizumab for a median of 31 months, about 50% were able to discontinue glucocorticoids (GC), indicating the efficacy of mepolizumab in managing this condition.

Patients who achieved GC-free status had higher absolute eosinophil counts at diagnosis and fewer gastrointestinal lesions, suggesting that while specific factors were not statistically significant, improvements in eosinophil counts and disease activity scores contributed to the reduction of GC use and protection against organ damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab exerts crucial effects on glucocorticoid discontinuation in patients with eosinophilic granulomatosis with polyangiitis: a retrospective study of 27 cases at a single center in Japan. Yamane, T., Hashiramoto, A.[2023]

In a study of 114 patients with active psoriatic arthritis (PsA) who started on guselkumab, 78.9% continued treatment after 6 months, showing strong treatment persistence.

Patients experienced significant improvements in joint and skin symptoms, with a mean reduction in disease activity index (cDAPSA) of -5.4 and notable decreases in pain and psoriasis severity, confirming guselkumab's efficacy in a real-world setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-Month Persistence and Multi-domain Effectiveness of Guselkumab in Adults with Psoriatic Arthritis: Real-World Data from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. Mease, PJ., Ogdie, A., Tesser, J., et al.[2023]

Secukinumab demonstrated significant efficacy in treating psoriatic arthritis (PsA), showing robust improvements across all core domains, including joint counts, enthesitis, and skin severity, in a pooled analysis of 2049 patients from multiple phase III studies.

At a dosage of 300 mg, secukinumab led to complete resolution of swollen joints in 34.3% of patients and significant improvements in other symptoms, indicating its potential as an effective treatment option for various manifestations of PsA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Secukinumab on the Different GRAPPA-OMERACT Core Domains in Psoriatic Arthritis: A Pooled Analysis of 2049 Patients. Orbai, AM., McInnes, IB., Coates, LC., et al.[2021]

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 study involving 1118 patients with active psoriatic arthritis (PsA), guselkumab significantly improved the resolution of enthesitis compared to placebo, with 45% and 50% of patients achieving resolution at week 24 for the Q4W and Q8W dosing regimens, respectively.

By week 52, 58% of patients treated with guselkumab had resolved their enthesitis, and those who achieved resolution were more likely to reach minimal disease activity, indicating that effective enthesitis treatment may lead to better overall patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resolution of enthesitis by guselkumab and relationships to disease burden: 1-year results of two phase 3 psoriatic arthritis studies. McGonagle, D., McInnes, IB., Deodhar, A., et al.[2021]

Citations

1. 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).

2. 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 ...

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/media/yh0ll4nt/final-press-release-depemokimab-swift.pdf

final-press-release-depemokimab-swift.pdf Depemokimab late-breaking data presented at ERS show a. 54% reduction in severe asthma exacerbations. • SWIFT-1 and SWIFT-2 phase III data ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11843704/

Heterogeneity and individualized therapy for eosinophilic ... Non-severe eosinophilic granulomatosis with polyangiitis: long-term outcomes after remission-induction trial. Rheumatology (Oxford) 2019; 58 ...

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. accp1.onlinelibrary.wiley.com accp1.onlinelibrary.wiley.com/doi/full/10.1002/cpdd.1506

Pharmacokinetics of Depemokimab Delivered by Safety ... Depemokimab is an ultra-long-acting biologic targeting human IL-5, showing approximately 29–fold increased potency and about a 2-fold reduction in clearance ...