OCEAN: Efficacy and Safety of Depemokimab Compared With Mepolizumab in Adults With Relapsing or Refractory Eosinophilic Granulomatosis With Polyangiitis (EGPA)
Study Details
Study Description
Brief Summary
This study aims to investigate the efficacy and safety of depemokimab compared with mepolizumab in adults with relapsing or refractory EGPA receiving SoC therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Participants receiving depemokimab+placebo matching mepolizumab
|
Biological: Depemokimab
Depemokimab will be administered
Drug: Placebo matching mepolizumab
Placebo matching to mepolizumab will be administered.
|
| Active Comparator: Participants receiving mepolizumab+placebo matching depemokimab
|
Biological: Mepolizumab
Mepolizumab will be administered
Drug: Placebo matching depemokimab
Placebo matching to depemokimab will be administered.
|
Outcome Measures
Primary Outcome Measures
- Number of participants with remission (Birmingham Vasculitis Activity Score [BVAS]=0 and a dose of oral corticosteroid [OCS] less than or equal to [<=]4 milligram [mg] per day) [Up to Week 52]
Participants must be in remission at both Week 36 and Week 52
Secondary Outcome Measures
- Number of participants in each category of accrued duration of remission [Up to Week 52]
Total accrued duration of remission is the accrued number of weeks where BVAS=0 plus OCS dose <=4 mg/day over the 52-week intervention period. The accrued duration was categorized into zero, >0 to <12 weeks, 12 to <24 weeks, 24 to <36 weeks or more than or equal to (>=) 36 weeks.
- Number of participants with total accrued duration of remission [Up to Week 52]
Total accrued duration of remission is the accrued number of weeks where BVAS=0 plus OCS dose <=4 mg/day over the 52-week intervention period.
- Time to first EGPA relapse [Up to Week 52]
The time to first EGPA relapse will be calculated from the date of first dose of study intervention and start date of the EGPA relapse.
- Number of participants receiving in each category of mean OCS dose during the last 4 weeks of study treatment period (Weeks 49 to 52) [Weeks 49 to 52]
Number of participants receiving the mean OCS dose (categorized as 0, >0 to <=4, >4 to <=7.5 or >7.5 mg/day) will be assessed during the last 4 weeks of the study treatment period (Weeks 49 to 52).
- Number of participants achieving remission (BVAS=0 and OCS <=4mg/day) within the first 24 weeks with continued remission until Week 52 [Up to Week 52]
- Number of participants achieving remission using the European League against Rheumatism (EULAR) definition (BVAS=0 and OCS <=7.5 mg/day) at Weeks 36 and 52 [At Weeks 36 and 52]
- Number of participants in each category of accrued duration of remission according to the EULAR definition of remission (BVAS=0 plus OCS <=7.5 mg/day) over 52-week intervention period [Up to Week 52]
Total accrued duration of remission according to the EULAR definition of remission is the accrued number of weeks where BVAS=0 plus OCS dose <=7.5 mg/day over the 52 week intervention period categorized as zero weeks; >0 to <12 weeks; 12 to <24 weeks; 24 to <36 weeks or >=36 weeks.
- Number of participants with total accrued duration of remission according to the EULAR definition of remission [Up to Week 52]
Total accrued duration of remission according to the EULAR definition of remission is the accrued number of weeks where BVAS=0 plus OCS <=7.5 mg/day over the 52-week intervention period.
- Number of participants with remission (BVAS=0 and OCS <=7.5 mg/day) within the first 24 weeks with continued remission until Week 52 [Up to Week 52]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant (male or female) must be 18 years of age or older at the time of signing the informed consent.
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Participants who are >=40 kilogram at Screening Visit 1.
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Participants who have been diagnosed with EGPA for at least 6 months based on the history or presence of: asthma plus eosinophilia defined as >1.0*10^9/Liter (L) and/or
10 percentage (%) of leucocytes plus at least 2 of the following additional features of EGPA: a biopsy showing histopathological evidence of eosinophilic vasculitis, or perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation, neuropathy, mono or poly (motor deficit or nerve conduction abnormality), pulmonary infiltrates, non-fixed, sino-nasal abnormality, cardiomyopathy (established by echocardiography or magnetic resonance imaging), glomerulonephritis (hematuria, red cell casts, proteinuria), alveolar hemorrhage (by bronchoalveolar lavage), palpable purpura, anti-neutrophil cytoplasmic antibodies positive Myeloperoxidase or Proteinase 3.
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History of relapsing OR refractory disease.
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Participants must be on a stable dose of oral prednisolone or prednisone of >=7.5 mg/day (but not >50 mg/day) for at least 4 weeks prior to Baseline (Visit 2).
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If participants receiving immunosuppressive therapy (excluding cyclophosphamide) the dosage must be stable for the 4 weeks prior to Baseline (Visit 2) and during the study.
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A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%.
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Capable of giving signed informed consent
Exclusion Criteria:
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Participants diagnosed with granulomatosis with polyangiitis; previously known as Wegener's granulomatosis or microscopic polyangiitis.
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Participants with organ-threatening EGPA as per EULAR criteria,
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Imminently life-threatening EGPA disease within 3 months prior to Screening (Visit 1).
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A current malignancy or previous history of cancer in remission for less than 12 months prior to Screening.
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Participants with alanine aminotransferase >2upper limit of normal (ULN) or if participant is on background methotrexate or azathioprine >3ULN, aspartate aminotransferase >2ULN or if participant is on background methotrexate or azathioprine >3ULN, alkaline phosphatase >=2.0ULN, total bilirubin >1.5ULN (isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%), Cirrhosis or current unstable liver or biliary disease per investigator assessment.
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Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
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Participants who have known, pre-existing, clinically significant system abnormalities that are not associated with EGPA and are uncontrolled with standard treatment.
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Clinically significant abnormality in the hematological, biochemical or urinalysis screen at Visit 1.
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Chronic or ongoing active infectious disease requiring systemic treatment.
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Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening Visit 1.
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A known immunodeficiency (e.g. human immunodeficiency virus [HIV]).
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Participants that, according to the investigator's medical judgment, are likely to have active coronavirus disease 2019 (COVID-19) infection. Participants with known COVID-19 positive contacts within the past 14 days must be excluded for at least 14 days following the exposure during which the participant must remain symptom-free.
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Participants with a known allergy or intolerance to a monoclonal antibody or biologic therapy or any of the excipients of the investigational products.
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Participants who have a previous documented failure with anti-Interleukin-5 /Interleukin-5 receptor therapy.
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Participants receiving any of the following: Oral corticosteroids: Participant requires an oral corticosteroid dose of >50 mg/day prednisolone/prednisone in the 4-week period prior to Baseline (Visit 2), Intravenous (IV), intramuscular or subcutaneous (SC) corticosteroids in the 4-week period prior to Baseline (Visit 2), Omalizumab within 130 days prior to Screening (Visit 1), Cyclophosphamide (CYC): oral CYC within 4 weeks prior to Baseline (Visit 2) and IV CYC within 3 weeks prior to Baseline (Visit 2), if their total white blood cells is >=4*10^9/L (measured using the local laboratory if necessary), Rituximab within 12 months prior to Screening (Visit 1); in addition, the Participant must have shown recovery of peripheral B-cell count to within the normal range, IV or SC immunoglobulin within 6 months prior to Screening (Visit 1); For China and Japan only within 12 weeks prior to Screening (Visit 1), Interferon-alpha within 6 months prior to Screening Visit 1, Anti-tumor necrosis factor therapy within 12 weeks prior to Screening Visit 1, Anti-CD52 (alemtuzumab) within 6 months prior to Screening Visit 1.
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Participants with 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Tulsa | Oklahoma | United States | 74136 |
| 2 | GSK Investigational Site | Norfolk | Virginia | United States | 23507 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 217102