Efficacy and Safety of Depemokimab Compared With Mepolizumab in Adults With Relapsing or Refractory Eosinophilic Granulomatosis With Polyangiitis (EGPA)

Eosinophilic Granulomatosis With Polyangiitis Clinical Trial

— OCEAN  

Official title:

A 52-week, Randomized, Double-blind, Double-dummy, Parallel-group, Multi-centre, Non-inferiority Study to Investigate the Efficacy and Safety of Depemokimab Compared With Mepolizumab in Adults With Relapsing or Refractory Eosinophilic Granulomatosis With Polyangiitis (EGPA) Receiving Standard of Care (SoC) Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05263934
• Other study ID #: 217102
• Status: Recruiting
• Phase: Phase 3
• Start date: July 14, 2022
• Est. completion date: November 7, 2025

Study information

• Verified date: October 2023
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: November 7, 2025
• Est. primary completion date: October 10, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant (male or female) must be 18 years of age or older at the time of signing the informed consent.
• Participants who are >=40 kilogram at Screening Visit 1.
• Participants with a documented diagnosis of 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.
• History of relapsing OR refractory disease.
• 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).
• 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.
• 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%.
• Capable of giving signed informed consent

Exclusion Criteria:

• Participants diagnosed with granulomatosis with polyangiitis; previously known as Wegener's granulomatosis or microscopic polyangiitis.
• Participants with organ-threatening EGPA as per EULAR criteria,
• Imminently life-threatening EGPA disease within 3 months prior to Screening (Visit 1).
• A current malignancy or previous history of cancer in remission for less than 12 months prior to Screening.
• Participants with alanine aminotransferase >2*upper limit of normal (ULN) or if participant is on background methotrexate or azathioprine >3*ULN, aspartate aminotransferase >2*ULN or if participant is on background methotrexate or azathioprine >3*ULN, alkaline phosphatase >=2.0*ULN, total bilirubin >1.5*ULN (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.
• Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
• Participants who have known, pre-existing, clinically significant system abnormalities that are not associated with EGPA and are uncontrolled with standard treatment.
• Clinically significant abnormality in the hematological, biochemical or urinalysis screen at Visit 1.
• Chronic or ongoing active infectious disease requiring systemic treatment.
• Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening Visit 1.
• A known immunodeficiency (e.g. human immunodeficiency virus [HIV]).
• 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.
• Participants with a known allergy or intolerance to a monoclonal antibody or biologic therapy or any of the excipients of the investigational products.
• Participants who have a previous documented failure with anti-Interleukin-5 /Interleukin-5 receptor therapy. Participants who have received monoclonal antibodies (mAb) and who have not undergone the required washout periods, prior to Visit 1.
• 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, Tezepelumab and Dupilumab with a washout period of 5 half-lives prior to Screening Visit 1, 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.
• 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 in the 12-lead ECG central over-read from at Screening Visit 1.

Related Conditions & MeSH terms

• Churg-Strauss Syndrome
• Eosinophilic Granulomatosis With Polyangiitis
• Granulomatosis with Polyangiitis
• Systemic Vasculitis

Intervention

Biological:
• Depemokimab
Depemokimab will be administered
• Mepolizumab
Mepolizumab will be administered

Drug:
• Placebo matching mepolizumab
Placebo matching to mepolizumab will be administered.
• Placebo matching depemokimab
Placebo matching to depemokimab will be administered.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	San Miguel de Tucuman	Tucumán
Australia	GSK Investigational Site	Canberra	Australian Capital Territory
Austria	GSK Investigational Site	Graz
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Leuven
Brazil	GSK Investigational Site	Santo André	São Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Guangzhou
China	GSK Investigational Site	Guangzhou
China	GSK Investigational Site	Hefei
China	GSK Investigational Site	Kunming	Yunnan
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Qingdao	Shandong
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shen Zhen	Guangdong
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Wenzhou
Czechia	GSK Investigational Site	Liben
Czechia	GSK Investigational Site	Praha
France	GSK Investigational Site	Angers Cedex 09
France	GSK Investigational Site	Brest Cedex
France	GSK Investigational Site	La Roche sur Yon Cedex 9
France	GSK Investigational Site	Lille Cedex
France	GSK Investigational Site	Montpellier cedex 5
France	GSK Investigational Site	Nantes Cedex 1
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Pessac
France	GSK Investigational Site	Suresnes
France	GSK Investigational Site	Toulouse
Germany	GSK Investigational Site	Freiburg	Baden-Wuerttemberg
Hungary	GSK Investigational Site	Budapest
Israel	GSK Investigational Site	Kfar Saba
Israel	GSK Investigational Site	Ramat-Gan
Italy	GSK Investigational Site	Bari	Puglia
Italy	GSK Investigational Site	Brescia	Lombardia
Italy	GSK Investigational Site	Firenze	Toscana
Italy	GSK Investigational Site	Milan	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Pisa	Toscana
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Torino
Italy	GSK Investigational Site	Torrette	Marche
Italy	GSK Investigational Site	Treviso	Veneto
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Chonju
Korea, Republic of	GSK Investigational Site	Gwangju
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Leiden, RC
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Warszawa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Porto
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Pamplona
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Zaragoza
Sweden	GSK Investigational Site	Malmö
United Kingdom	GSK Investigational Site	Birmingham
United Kingdom	GSK Investigational Site	Cambridge
United Kingdom	GSK Investigational Site	London
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Norfolk	Virginia
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Rochester	Minnesota
United States	GSK Investigational Site	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Participants must be in remission at both Weeks 36 and 52.	Up to Week 52
Secondary	Number of participants in each category of accrued duration of remission	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.	Up to Week 52
Secondary	Number of participants with total accrued duration of remission	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.	Up to Week 52
Secondary	Time to first EGPA relapse	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.	Up to Week 52
Secondary	Number of participants receiving in each category of mean OCS dose during the last 4 weeks of study treatment period (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).	Weeks 49 to 52
Secondary	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
Secondary	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
Secondary	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	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.	Up to Week 52
Secondary	Number of participants with total accrued duration of remission according to the EULAR definition of remission	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.	Up to Week 52
Secondary	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

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