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

NCT05263934 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 2171022023-510019-20-00
• Study Type: interventional
• Target: 163
• Locations: 20 countries
• Sites: 76

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.

Conditions

Eosinophilic Granulomatosis With Polyangiitis

Keywords

Depemokimab; Mepolizumab; Eosinophilic Granulomatosis with Polyangiitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Number of participants in each category of accrued duration of remission

  Up to Week 52

• Number of participants with total accrued duration of remission

  Up to Week 52

• Time to first EGPA relapse

  Up to Week 52

• 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 achieving remission (BVAS = 0 and OCS <= 4 mg/day) within the first 24 weeks with continued remission until Week 52

  Up to Week 52

Study Arms (2)

Participants receiving depemokimab+placebo matching mepolizumab

EXPERIMENTAL

Biological: Depemokimab; Drug: Placebo matching mepolizumab

Participants receiving mepolizumab+placebo matching depemokimab

ACTIVE COMPARATOR

Biological: Mepolizumab; Drug: Placebo matching depemokimab

Interventions

Depemokimab BIOLOGICAL

Depemokimab will be administered

Participants receiving depemokimab+placebo matching mepolizumab

Mepolizumab BIOLOGICAL

Mepolizumab will be administered

Participants receiving mepolizumab+placebo matching depemokimab

Placebo matching mepolizumab DRUG

Placebo matching to mepolizumab will be administered.

Participants receiving depemokimab+placebo matching mepolizumab

Placebo matching depemokimab DRUG

Placebo matching to depemokimab will be administered.

Participants receiving mepolizumab+placebo matching depemokimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) or equivalent 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

You may not qualify if:

• 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 (e.g., mepolizumab, reslizumab, benralizumab). 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (76)

GSK Investigational Site

Denver, Colorado, 80206, United States

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GSK Investigational Site

Gainesville, Florida, 32610, United States

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GSK Investigational Site

Rochester, Minnesota, 55905, United States

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GSK Investigational Site

New York, New York, 10021, United States

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GSK Investigational Site

Charlotte, North Carolina, 28211, United States

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GSK Investigational Site

Tulsa, Oklahoma, 74136, United States

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GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

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GSK Investigational Site

Pittsburgh, Pennsylvania, 15261, United States

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GSK Investigational Site

Norfolk, Virginia, 23507, United States

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GSK Investigational Site

La Plata, B1900, Argentina

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GSK Investigational Site

San Miguel de Tucumán, T4000, Argentina

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GSK Investigational Site

Graz, 8036, Austria

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GSK Investigational Site

Brussels, 1070, Belgium

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GSK Investigational Site

Leuven, 3000, Belgium

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GSK Investigational Site

São Paulo, 4023900, Brazil

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GSK Investigational Site

Toronto, Ontario, M5T 3A9, Canada

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GSK Investigational Site

Toronto, Ontario, M5T 3L9, Canada

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GSK Investigational Site

Beijing, 100005, China

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GSK Investigational Site

Guangzhou, 510163, China

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GSK Investigational Site

Hefei, 230001, China

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GSK Investigational Site

Nanjing, 210006, China

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GSK Investigational Site

Qingdao, 266071, China

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GSK Investigational Site

Shanghai, 200032, China

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GSK Investigational Site

Shenzhen, 518020, China

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GSK Investigational Site

Wenzhou, 325000, China

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GSK Investigational Site

Brest, 29609, France

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GSK Investigational Site

La Roche-sur-Yon, 85925, France

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GSK Investigational Site

Lille, 59037, France

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GSK Investigational Site

Montpellier, 34295, France

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GSK Investigational Site

Nantes, 44093, France

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GSK Investigational Site

Paris, 75014, France

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GSK Investigational Site

Suresnes, 92150, France

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GSK Investigational Site

Toulouse, 31059, France

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GSK Investigational Site

Freiburg im Breisgau, 79106, Germany

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GSK Investigational Site

Minden, 32429, Germany

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GSK Investigational Site

Budapest, 1023, Hungary

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GSK Investigational Site

Ramat Gan, 52621, Israel

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GSK Investigational Site

Bari, 70124, Italy

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GSK Investigational Site

Brescia, 25123, Italy

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GSK Investigational Site

Florence, 50134, Italy

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GSK Investigational Site

Milan, 20132, Italy

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GSK Investigational Site

Milan, 20162, Italy

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GSK Investigational Site

Pavia, 27100, Italy

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GSK Investigational Site

Pisa, 56126, Italy

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GSK Investigational Site

Roma, 00128, Italy

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GSK Investigational Site

Torrette AN, 60126, Italy

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GSK Investigational Site

Treviso, 31100, Italy

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GSK Investigational Site

Kanagawa, 247-8533, Japan

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GSK Investigational Site

Kanagawa, 252-0392, Japan

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GSK Investigational Site

Saitama, 350-8550, Japan

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GSK Investigational Site

Tokyo, 162-8666, Japan

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GSK Investigational Site

Tokyo, 181-8611, Japan

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GSK Investigational Site

Groningen, 9713 GZ, Netherlands

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GSK Investigational Site

Leiden, 2333 ZA, Netherlands

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GSK Investigational Site

Gdansk, 80-952, Poland

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GSK Investigational Site

Lodz, 90-153, Poland

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GSK Investigational Site

Warsaw, 01-138, Poland

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GSK Investigational Site

Lisbon, 1649-035, Portugal

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GSK Investigational Site

Porto, 4099-001, Portugal

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GSK Investigational Site

Gwangju, 61469, South Korea

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GSK Investigational Site

Seoul, 05505, South Korea

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GSK Investigational Site

Seoul, 06351, South Korea

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GSK Investigational Site

Seoul, 06591, South Korea

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GSK Investigational Site

Seoul, 3080, South Korea

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GSK Investigational Site

Badalona, 08930, Spain

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GSK Investigational Site

Barcelona, 08035, Spain

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Granada, 18014, Spain

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GSK Investigational Site

Granada, 18016, Spain

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GSK Investigational Site

Pamplona, 31008, Spain

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GSK Investigational Site

Valencia, 46026, Spain

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GSK Investigational Site

Zaragoza, 50009, Spain

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GSK Investigational Site

Malmo, SE-205 02, Sweden

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GSK Investigational Site

Birmingham, B15 2GW, United Kingdom

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GSK Investigational Site

Cambridge, CB2 2QQ, United Kingdom

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GSK Investigational Site

London, SE1 7EH, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Churg-Strauss Syndrome

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will receive either depemokimab plus placebo matching mepolizumab or mepolizumab plus placebo matching depemokimab

Study Record Dates

• First Submitted: February 28, 2022
• First Posted: March 3, 2022
• Study Start: July 14, 2022
• Primary Completion (Estimated): September 29, 2026
• Study Completion (Estimated): October 27, 2026
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

PT (2); JP (5); NL (2); FR (8); CN (8); HU (1); IL (1); KR (5); US (9); IT (10); AR (2); BE (2); AU (1); ES (8); CA (2); DE (2); SE (1); GB (3); BR (1); PL (3)