A study to investigate the efficacy and safety of depemokimab compared with mepolizumab in adults with relapsing or refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Phase 1

Recruiting

• Conditions: Relapsing or refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA) receiving standard of care (SoC) therapy; MedDRA version: 20.0Level: PTClassification code: 10078117Term: Eosinophilic granulomatosis with polyangiitis Class: 100000004870; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: CTIS2023-510019-20-00
• Lead Sponsor: Glaxosmithkline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-16
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

Participant (male or female) must be 18 years or older at the time of signing the informed consent., Participants who are = 40 kg 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 in this study as >1.0x109/L and/or >10% 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 [MRI]) • glomerulonephritis (haematuria, red cell casts, proteinuria) • alveolar haemorrhage (by bronchoalveolar lavage) • palpable purpura • ANCA positive Myeloperoxidase (MPO) or Proteinase 3 (PR3)., History of relapsing OR refractory disease defined as: • Relapsing disease: Participants must have a history of at least one confirmed EGPA relapse (i.e., requiring increase in oral corticosteroid (OCS) dose, initiation/increased dose of immunosuppressive therapy or inpatient hospitalisation due to EGPA) within the past 2 years. EGPA relapse should have occurred at least 12 weeks or more prior to Screening (Visit 1) whilst receiving a dose of prednisolone (or equivalent of) =7.5 mg/day. • China and Japan only definition of Relapsing disease: Participant must have a history of at least one confirmed EGPA relapse (i.e., requiring increase in OCS dose, initiation of IV prednisolone (or equivalent), initiation/increased dose of immunosuppressive therapy, initiation/increased dose of intravenous immunoglobulin (IVIG) or hospitalisation) within the past 2 years which occurred at least 12 weeks prior to Screening (Visit 1) whilst receiving a dose of prednisolone (or equivalent of) =7.5 mg/day. • Refractory disease: Defined as either: o Failure to attain remission (BVAS=0 and OCS dose =7.5 mg/day prednisolone or equivalent) within the last 6 months prior to Screening Visit 1 and following induction treatment with a standard OCS regimen, administered for at least 3 months OR o Participants with recurrence of EGPA symptoms within 6 months prior to Screening (Visit 1) whilst tapering OCS and occurring at any dose level =7.5 mg/day prednisolone or equivalent., 'Corticosteroid therapy: 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)., Immunosuppressive therapy: If 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 nonchildbearing potential (WONCBP) • Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, from at least 14 days prior to the first dose of study intervention until the following durations (whichever is greater): o 30 weeks after the last potential administration of depemokimab at Week 1 or Week 26, o 16 weeks after the last potential administration of mepolizumab (remaining administrations)., Capable of giving signed informed conse

Exclusion Criteria

Diagnosed with granulomatosis with polyangiitis or MPA., Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening Visit 1., A known immunodeficiency (e.g. HIV), other than that explained by the use of OCS or other immunosuppressants taken as therapy for EGPA., COVID-19: Participants that, according to the investigator's medical judgment, are likely to have active 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., Hypersensitivity: Participants with a known allergy or intolerance to a monoclonal antibody or biologic therapy or any of the excipients of the investigational products listed in Section 6.1., Monoclonal antibodies • Monoclonal antibodies targeting IL-5/5R: Participants who have a previous documented failure with anti-IL-5/5R therapy, based on investigator's discretion. • Participants who have received mAb who have not undergone the required washout periods, prior to Visit 1., Investigational Medications/clinical study: • Participants who have received treatment with investigational drug within the past 30 days or 5 terminal phase half-lives of the drug whichever is longer, prior to Visit 1 (this also includes investigational formulations of marketed products). • Participants who are currently participating in any other interventional clinical study., Participants receiving other prohibited medications., Previous participation in any study with mepolizumab, reslizumab, or benralizumab and received study intervention (including placebo) within 6 months prior to Screening Visit 1., ECG Assessment: QTcF =450 msec or QTcF =480 msec for participants with Bundle Branch Block in the 12-lead ECG central overread from Screening Visit 1., Alcohol/Substance Abuse, EULAR defined organ-threatening EGPA: Organ-threatening EGPA as per EULAR criteria, i.e., organ failure due to active vasculitis, creatinine >5.8 g/dL (>513 µmol/L) within 3 months prior to Screening (Visit 1)., Pregnancy, Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations., Imminently life-threatening EGPA disease defined as any of the following within 3 months prior to Screening (Visit 1): • Intensive care required • Severe alveolar haemorrhage or haemoptysis requiring transfusion or ventilation or haemoglobin <8 g/dL (<80 g/L) or drop in haemoglobin >2 g/dL (>20 g/L) over a 48 hours period due to alveolar haemorrhage • Rapidly progressive glomerulonephritis (RPGN) with creatinine >2.5 mg/dL (>221 µmol/L) or rise in creatinine >2 mg/dL (>177 µmol/L) over a 48 hour period • Severe GI involvement, e.g., gangrene, bleeding requiring surgery • Severe CNS involvement • Severe cardiac involvement, A current malignancy or previous history of cancer in remission for less than 12 months prior to screening. Participants that had localised carcinoma of the skin which was resected for cure will not be excluded., Liver Disease: • Alanine aminotransferase (ALT) >2x upper limit of normal (ULN) or if participant is on background methotrexate or azathioprine >3x ULN • AST >2x ULN or if participant is on background methotrexate or azathioprine >3x ULN • Alkaline Phosphatase =2.0x ULN • Total bilirubin >1.5x ULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) • Ci

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of depemokimab SC every 26 weeks compared with mepolizumab SC every 4 weeks in participants with relapsing or refractory EGPA receiving SoC therapy.;Secondary Objective: To evaluate the efficacy of depemokimab SC every 26 weeks compared with mepolizumab SC every 4 weeks on additional efficacy assessments in participants with relapsing or refractory EGPA receiving SoC therapy;Primary end point(s): Remission (i.e., a Birmingham Vasculitis Activity Score (BVAS)=0 and a dose of oral corticosteroids (OCS) =4mg/day) at both Week 36 and Week 52.