A study to investigate the efficacy and safety of depemokimab compared with mepolizumab in adults with relapsing or refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA)
- Conditions
- Relapsing or refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA) receiving standard of care (SoC) therapyMedDRA version: 20.0Level: PTClassification code 10078117Term: Eosinophilic granulomatosis with polyangiitisSystem Organ Class: 10021428 - Immune system disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2021-005726-15-PT
- Lead Sponsor
- GlaxoSmithKline Research & Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 192
1. Participant (male or female) must be 18 years or older at the time of signing the informed consent.
2. Participants who are = 40 kg at Screening Visit 1.
3. Participants who have been diagnosed with 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).
4. 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.
5. 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).
6. 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.
7. 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).
8. Capable of giving signed
1. Diagnosed with granulomatosis with polyangiitis (GPA; previously known as Wegener’s granulomatosis) or microscopic polyangiitis (MPA).
2. 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).
3. 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 gastrointestinal (GI) involvement, e.g., gangrene, bleeding requiring surgery
• Severe central nervous system (CNS) involvement
• Severe cardiac involvement, e.g., life-threatening arrhythmia, cardiac failure: ejection fraction <20%, New York Heart Association Class III/IV, acute myocardial infarction.
4. 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.
5. 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%)
• Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice.
6. Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment including but not limited to:
• Known ejection fraction of <20%, OR
• Severe heart failure that meets New York Heart Association Class IV, OR
• Hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III OR
• Myocardial infarction or angina diagnosed less than 3 months prior to or at Screening Visit 1 OR
• Uncontrolled life threatening arrythmia within 3 months prior to or at Screening Visit 1).
7. Participants who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory or any other system abnormalities that are not associated with EGPA and are uncontrolled with standard treatment.
8. Evidence of clinically significant abnormality in the haematological, biochemical or urinalysis screen at Visit 1, as judged by the investigator.
9. Infectious disease: Chronic or ongoing active infectious disease requiring systemic treatment.
10. Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening Visit 1.
11. A known immunodeficiency (e.g. HIV), other than that explained by the use of OCS or other immunosuppressants taken as therapy for EGPA.
12. COVID-19: Participants that, according to the investigator's medical judgment, are likely to have active COV
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method