Depemokimab vs Mepolizumab for Granulomatosis with Polyangiitis

(OCEAN Trial)

Recruiting at 85 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: GlaxoSmithKline

Must be taking: Oral corticosteroids

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

Disqualifiers: Cancer, Cardiovascular disease, Immunodeficiency, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing two medications, depemokimab and mepolizumab, to see if they can help adults with a difficult-to-treat inflammatory condition called EGPA by reducing inflammation. Mepolizumab was previously approved for the treatment of EGPA.

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.

What data supports the effectiveness of the drug Depemokimab or Mepolizumab for treating Granulomatosis with Polyangiitis?

The research mentions that mepolizumab, when used as a fixed-dose subcutaneous injection, shows modest benefits in patients who depend on prednisone (a type of steroid) but have uncontrolled sputum eosinophilia (a condition where a type of white blood cell is present in high amounts in the lungs). This suggests that mepolizumab may have some effectiveness in managing conditions related to immune system dysfunction. ^{1 2 3 4 5}

How does the drug Depemokimab differ from Mepolizumab for treating Granulomatosis with Polyangiitis?

Depemokimab is being compared to Mepolizumab, which is already known to help reduce the need for steroids in treating eosinophilic granulomatosis with polyangiitis (EGPA). Mepolizumab works by targeting a specific protein involved in inflammation, and the trial aims to see if Depemokimab offers similar or better benefits. ^{6 7 8 9 10}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Depemokimab (Monoclonal Antibodies)
• Mepolizumab (Monoclonal Antibodies)

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.

Participant Groups

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

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 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 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]

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]

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 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]

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. England 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. [2020]

3. England 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. [2023]

4. England 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. [2021]

5. Canada pubmed.ncbi.nlm.nih.gov

Effect of Secukinumab on the Different GRAPPA-OMERACT Core Domains in Psoriatic Arthritis: A Pooled Analysis of 2049 Patients. [2021]

6. England 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. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of Low-Dose Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA): A Real-Life Experience. [2023]

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

Safety and effectiveness of mepolizumab therapy in remission induction therapy for eosinophilic granulomatosis with polyangiitis: a retrospective study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of mepolizumab in combination with corticosteroids in patients with eosinophilic granulomatosis with polyangiitis. [2021]

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

Clinical Benefit of Mepolizumab in Eosinophilic Granulomatosis With Polyangiitis for Patients With and Without a Vasculitic Phenotype. [2023]