Efficacy and safety of depemokimab compared with mepolizumab in adults with relapsing or refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA)
- Conditions
- Eosinophilic granulomatosis with polyangiitis for which Standard of care is insufficient.
- Registration Number
- JPRN-jRCT2031220070
- Lead Sponsor
- Fujii Katsuya
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 9
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Participant (male or female) must be 18 years or older at the time of signing the informed consent.
Weight
2. Participants who are >=40 kg at Screening Visit 1.
Type of Participant and Disease Characteristics
3. EGPA diagnosis: 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 >1.0x10x9/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 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:
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
NOTE:
- Participants who have received a cyclophosphamide (CYC) induction regimen may be included a minimum of 4 weeks after the last dose of daily oral CYC or pulsed IV CYC prior to Baseline (Visit 2), if their total white blood cells (WBC) is >=4x10x9/L (tested at the local laboratory, if necessary) prior to randomization.
- Participants who have received a methotrexate, azathioprine, or mycophenolate mofetil induction regimen may be included if on a stable dose for at least 4 weeks prior to Baseline (Visit 2).
- Participants who have received an induction regimen comprising corticosteroids alone may be included only if they have failed to attain remission after 3 months of treatment AND the corticosteroid dose is >=15 mg/day prednisolone or equivalent for the 4 weeks prior to Baseline (Visit 2).
OR
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. NOTE: Recurrent symptoms of EGPA do not necessarily need to meet
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. GPA or MPA: Diagnosed with granulomatosis with polyangiitis (GPA; previously known as Wegeners 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 micro mol/L) within 3 months prior to Screening (Visit 1).
3. Life-threatening EGPA: 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 micro mol/L) or rise in creatinine >2 mg/dL (>177 micro mol/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. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening. Participants that had localised carcinoma (i.e., basal or squamous cell) 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.
NOTE: Stable non-cirrhotic chronic liver disease (including Gilberts syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C), are acceptable if participant otherwise meets entry criteria.
6. Cardiovascular: 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. Other Concurrent Medical Conditions: 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. Laboratory abnormality: Evidence of clinically significant abnormality in the haematological, biochemical or urinalysis screen at Visit 1, as judged by the
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method