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

• Status: Not yet recruiting
• Trial end date: 2025-11-07
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline

Criteria

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 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.

• 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 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.

• 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.