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
- Conditions
- EGPAEosinophylic Granulomatosis with Polyangiitis10003816
- Registration Number
- NL-OMON53511
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 4
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 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).
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
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 exp
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Remission (i.e., a Birmingham Vasculitis Activity Score (BVAS)=0 and a dose of<br /><br>oral corticosteroids (OCS) <=4mg/day) at both Week 36 and Week 52</p><br>
- Secondary Outcome Measures
Name Time Method