Status:

ACTIVE_NOT_RECRUITING

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

Lead Sponsor:

GlaxoSmithKline

Conditions:

Eosinophilic Granulomatosis With Polyangiitis

Eligibility:

All Genders

18+ years

Phase:

PHASE3

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.

Eligibility Criteria

Inclusion

  • 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

Exclusion

  • 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.
  • 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.

Key Trial Info

Start Date :

July 14 2022

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

October 27 2026

Estimated Enrollment :

163 Patients enrolled

Trial Details

Trial ID

NCT05263934

Start Date

July 14 2022

End Date

October 27 2026

Last Update

November 20 2025

Active Locations (76)

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Page 1 of 19 (76 locations)

1

GSK Investigational Site

Denver, Colorado, United States, 80206

2

GSK Investigational Site

Gainesville, Florida, United States, 32610

3

GSK Investigational Site

Rochester, Minnesota, United States, 55905

4

GSK Investigational Site

New York, New York, United States, 10021