ACTIVE_NOT_RECRUITING

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

Conditions

Eosinophilic Granulomatosis With Polyangiitis Depemokimab Mepolizumab

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study aims to investigate the efficacy and safety of depemokimab compared with mepolizumab in adults with relapsing or refractory EGPA receiving SoC therapy.

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

Quick Facts

Study Start:2022-07-14

Study Completion:2026-10-27

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05263934

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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.

Inclusion Criteria

Exclusion 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

* 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.

Contacts and Locations

Principal Investigator

GSK Clinical Trials

STUDY_DIRECTOR

GlaxoSmithKline

Study Locations (Sites)

GSK Investigational Site

Denver, Colorado, 80206

United States

GSK Investigational Site

Gainesville, Florida, 32610

United States

GSK Investigational Site

Rochester, Minnesota, 55905

United States

GSK Investigational Site

Manhasset, New York, 11030

United States

GSK Investigational Site

New York, New York, 10021

United States

GSK Investigational Site

Charlotte, North Carolina, 28211

United States

GSK Investigational Site

Tulsa, Oklahoma, 74136

United States

GSK Investigational Site

Philadelphia, Pennsylvania, 19104

United States

GSK Investigational Site

Pittsburgh, Pennsylvania, 15261

United States

GSK Investigational Site

Norfolk, Virginia, 23507

United States

Collaborators and Investigators

Sponsor: GlaxoSmithKline

GSK Clinical Trials, STUDY_DIRECTOR, GlaxoSmithKline

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-07-14

Study Completion Date2026-10-27

Study Record Updates

Study Start Date2022-07-14

Study Completion Date2026-10-27

Terms related to this study

Keywords Provided by Researchers

Depemokimab
Mepolizumab
Eosinophilic Granulomatosis with Polyangiitis

Additional Relevant MeSH Terms

Eosinophilic Granulomatosis With Polyangiitis