A Study to Investigate Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02020889
• Date of registration: 19/12/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Study to Investigate Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis
• Scientific title: A Double-blind, Randomised, Placebo-controlled Study to Investigate the Efficacy and Safety of Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis in Subjects Receiving Standard of Care Therapy
• Date of first enrolment: February 5, 2014
• Target sample size: 136
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02020889
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Belgium, Canada, France, Germany, Italy, Japan, Spain, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Informed Consent: Able to give written informed consent prior to participation in the
study, which will include the ability to comply with the requirements and restrictions
listed in the consent form. Subjects must be able to read, comprehend, and write at a
level sufficient to complete study related materials.

- Age and gender: Male or female subjects age 18 years or older.

- EGPA diagnosis: subjects who have been diagnosed with EGPA for at least 6 months based
on the history or presence of: asthma plus eosinophilia (>1.0x10^9/Liter and/or >10%
of leucocytes) plus at least two 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 (haematuria, red cell casts,
proteinuria); alveolar haemorrhage (by bronchoalveolar lavage); palpable purpura; anti
neutrophil cytoplasmic anti-body (ANCA) positive (Myeloperoxidase or proteinease 3).

- History of relapsing OR refractory disease defined as: Relapsing disease:

Subject must have a past history of at least one confirmed EGPA relapse (i.e., requiring
increase in oral corticosteroids (OCS) dose, initiation/increased dose of immunosuppressive
therapy 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
milligram per day (mg/day). Refractory disease: Either: Failure to attain remission (BVAS=0
and OCS dose <=7.5 mg/day prednisolone or equivalent) within the last 6 months following
induction treatment with a standard regimen, administered for at least 3 months. Note: a)
Subjects who have received a cyclophosphamide (CYC) induction regimen may be included a
minimum of 2 weeks after the last dose of daily oral CYC, or 3 weeks after the last dose of
pulsed intravenous CYC prior to Baseline (Visit 2), if their total white blood cells (WBC)
is >=4x10^9/Liter (tested at the local laboratory, if necessary) prior to randomisation. b)
Subjects 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). c) Subjects 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: Within 6 months prior to Screening (Visit 1), recurrence of
symptoms of EGPA (not necessarily meeting the protocol definition of relapse) whilst
tapering OCS, occurring at any dose level >=7.5 mg/day prednisolone or equivalent.

- Corticosteroid therapy: Subject 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 (dose reductions for safety reasons will be permitted).

- ECG measurements: QTc(F)<450 msec or QTc(F)<480 msec for patients with bundle branch
block. The QTc is the QT interval corrected for heart rate according to either
Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or
manual overread. For subject eligibility and withdrawal decisions, QTcFwill be used.
For purposes of data analysis, QTcF will be used as primary though data using both
correction formulas will be collected and analysed. The QTc should be based on single
or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief
recording period.

- Female subjects: To be eligible for entry into the study, females of childbearing
potential (FCBP) must commit to consistent and correct use of an acceptable method of
birth control (as discussed in the protocol) beginning with consent, for the duration
of the trial and for 4 months after the last study drug administration.

- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category.

- Liver Function Tests: obtained at Screening (Visit 1): ALT<2x ULN (upper limit of
normal) or if subject is on background methotrexate or azathioprine <3x ULN; AST<2x
ULN or if subject is on background methotrexate or azathioprine <3x ULN; Alkaline
Phosphatase =2.0x ULN;Bilirubin = 1.5x ULN (isolated bilirubin>1.5x ULN is acceptable
if bilirubin is fractionated and direct bilirubin <35%)

Exclusion Criteria:

- GPA or MPA: Diagnosed with granulomatosis with polyangiitis (GPA; previously known as
Wegener's granulomatosis) or microscopic polyangiitis (MPA).

- Organ-threatening EGPA: Organ-threatening EGPA as per European league against
rheumatism (EULAR) criteria, i.e., organ failure due to active vasculitis, creatinine
>5.8 gram per deciliter (g/dL) (>513 micromole per liter [µmol/L]) within 3 months
prior to Screening (Visit 1).

- 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 gram per liter (g/dL) (<80 g/L) or drop in haemoglobin > 2 g/dL (>20
g/L) over a 48 hour period due to alveolar haemorrhage; Rapidly progressive
glomerulonephritis (RPGN) with creatinine > 2.5 milligram per deciliter (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 (as discussed in protocol), acute myocardial infarction.

- Malignancy: A current malignancy or previous history of cancer in remission for less
than 12 months prior screening (Subjects that had localized carcinoma (i.e., basal or
squamous cell) of the skin which was resected for cure will not be excluded).

- Liver disease: Unstable liver disease (as defined by the presence of ascites,



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Churg-Strauss Syndrome

Intervention(s)

Biological: Mepolizumab

Drug: Placebo

Primary Outcome(s)

Number of Participants in Each Category of Accrued Duration of Remission [Time Frame: Up to Week 52]

Number of Participants Who Are in Remission at 36 and 48 Weeks [Time Frame: Week 36 and Week 48]

Secondary Outcome(s)

Change From Baseline in Clinical Chemistry Parameters of Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.), Aspartate Aminotransferase (AST), Creatinine Kinase, Gamma Glutamyl Transaminase (GGT) and Lactate Dehydrogenase (Dehydro) Levels [Time Frame: Baseline and up to Week 60]

Change From Baseline in Hematology Parameters of Erythrocytes Levels [Time Frame: Baseline and up to Week 60]

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Levels [Time Frame: Baseline up to Week 60]

Maximum Change From Baseline in QTcF and QTcB Values [Time Frame: Baseline and up to Week 60]

Number of Participants Who Achieved Remission (BVAS=0 and Prednisolone/Prednisone <=7.5 mg/Day) Within the First 24 Weeks and Remained in Remission for the Remainder of the Treatment Period [Time Frame: Up to Week 52]

Change From Baseline in Body Temperature [Time Frame: Baseline and up to Week 60]

Change From Baseline in Hematology Parameters of Basophils, Eosinophil, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Levels [Time Frame: Baseline and up to Week 60]

Change From Baseline in Hematology Parameters of Mean Corpuscle Hemoglobin (MCH) Levels [Time Frame: Baseline and up to Week 60]

Number of Participants in Each Category of Accrued Duration of Remission [Time Frame: Up to Week 52]

Number of Participants Who Achieved Remission Within the First 24 Weeks and Remained in Remission for the Remainder of the Treatment Period [Time Frame: Up to Week 52]

Change From Baseline in Hematology Parameters of Mean Corpuscle Volume (MCV) Levels [Time Frame: Baseline and up to Week 60]

Mean Change From Baseline in QT Interval Corrected by Fridericia's Method (QTcF) and QT Interval Corrected by Bazett's Method (QTcB) Values [Time Frame: Baseline and up to Week 60]

Change From Baseline in Hematology Parameters of Mean Corpuscle Hemoglobin Concentration (MCHC) and Hemoglobin Levels [Time Frame: Baseline and up to Week 60]

Change From Baseline in Clinical Chemistry Parameters of Albumin and Protein Levels [Time Frame: Baseline and up to Week 60]

Time to First EGPA Relapse [Time Frame: Up to Week 52]

Number of Participants With Anti-Mepolizumab Antibodies [Time Frame: Up to Week 60]

Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Phosphorus, Potassium, Sodium, Urea Nitrogen and Very Low Density Lipoprotein (VLDL) Cholesterol Levels [Time Frame: Baseline and up to Week 60]

Number of Participants in Each Category of Average Daily Prednisolone/Prednisone Dose During the Last 4 Weeks of the Study Treatment Period. [Time Frame: Week 48 and Week52]

Number of Participants With Local and Systemic Adverse Events (AEs) [Time Frame: Up to Week 52]

Change From Baseline in Clinical Chemistry Parameters of Direct, Indirect and Total Bilirubin and Creatinine Levels [Time Frame: Baseline and up to Week 60]

Change From Baseline in Clinical Chemistry Parameter of Troponin Levels [Time Frame: Baseline and up to Week 60]

Number of Participants Who Are in Remission at 36 and 48 Weeks [Time Frame: Week 36 and Week 48]

Change From Baseline in Pulse Rate [Time Frame: Baseline and up to Week 60]

Secondary ID(s)

115921

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institute of Allergy and Infectious Diseases (NIAID)

Results

• Results available: Yes
• Date Posted: 26/01/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02020889