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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02020889
Other study ID # 115921
Secondary ID
Status Completed
Phase Phase 3
First received December 19, 2013
Last updated January 29, 2018
Start date February 5, 2014
Est. completion date September 5, 2016

Study information

Verified date January 2018
Source GlaxoSmithKline
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this randomized, double-blind study is to investigate the efficacy and safety of mepolizumab (300 milligram [mg] administered subcutaneously [SC] every 4 weeks) compared with placebo over a 52-week study treatment period in subjects with relapsing or refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA) receiving standard of care therapy including background corticosteroid therapy with or without immunosuppressive therapy. During the treatment period, in accordance with standard of care, corticosteroid dose will be tapered. The key outcomes in the study focus on evaluation of clinical remission, defined as Birmingham Vasculitis Activity Score (BVAS)=0 with a corticosteroid dose of <=4 mg/day prednisolone/prednisone, reduction in disease relapse and reduction in corticosteroid requirement.


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Study Design


Intervention

Biological:
Mepolizumab
Mepolizumab will be provided as a lyophilized cake in sterile vials for individual use to be reconstituted with sterile water for Injection, just prior to use.
Drug:
Placebo
Placebo will be available as 0.9% sodium chloride

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Sponsors (2)

Lead Sponsor Collaborator
GlaxoSmithKline National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants in Each Category of Accrued Duration of Remission Total accrued duration of remission is the accrued number of weeks where Birmingham Vasculitis Activity Score (BVAS) =0 plus prednisolone/prednisone dose <=4 mg/day over the 52 week study treatment period was reported. The accrued duration was categorized into zero, >0 to <12 weeks, 12 to <24 weeks, 24 to <36 weeks and >=36 weeks. Statistical analysis was based on a proportional odds regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region. Intent-to-Treat (ITT) Population was used for the analysis and was defined as all participants who were randomized and received at least one dose of trial medication. Randomized participants were assumed to have received study treatment unless definitive evidence to the contrary exists. The odds ratio for treatment difference and associated probability (p)-value and 95 percent confidence interval (CI) were calculated. Up to Week 52
Primary Number of Participants Who Are in Remission at 36 and 48 Weeks The number of participants who were in remission (i.e ., BVAS=0 and prednisolone /prednisone <=4 mg/day) at both Weeks 36 and 48 of the study treatment period was reported. The statistical analysis was performed using a logistic regression model on ITT Population. The odds ratio for treatment difference and associated p-value and 95 percent CI were calculated. Week 36 and Week 48
Secondary Time to First EGPA Relapse EGPA relapse was defined as worsening or persistence of active disease since the last visit characterized by active vasculitis or active asthma symptoms and/or signs with a corresponding worsening in Asthma Control Questionnaire-6 (ACQ-6) score or active nasal and/or sinus disease, with a corresponding worsening in at least one of the sino-nasal symptom questions warranting: i) an increased dose of OCS therapy (or other systemic corticosteroid therapy) to >4 mg/day prednisolone total daily dose or equivalent; OR ii) an increased dose or addition of immunosuppressive therapy; OR iii) hospitalization related to EGPA worsening. Participants who completed study, or withdrawn prematurely from the study without experiencing the event were censored. The number of participants with at least one EGPA relapse during the planned study treatment period are presented. Up to Week 52
Secondary Number of Participants in Each Category of Average Daily Prednisolone/Prednisone Dose During the Last 4 Weeks of the Study Treatment Period. The number of participants with an average daily prednisolone/prednisone dose during the last 4 weeks of the Study Treatment Period (48 through 52) was calculated. The average dose was categorized into zero, >0 to <=4.0mg, >4.0 to <=7.5mg and >7.5mg. The statistical analysis was performed using a proportional odds regression model with Baseline covariates of treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region and the comparison between treatment groups was presented as an odds ratio, p-value and 95 percent CI. Week 48 and Week52
Secondary Number of Participants Who Achieved Remission Within the First 24 Weeks and Remained in Remission for the Remainder of the Treatment Period The number of participants who achieved remission (i.e., BVAS=0 and prednisolone/prednisone<=4 mg/day) within the first 24 weeks and remain in remission for the remainder of the study treatment period was reported. The statistical analysis was performed using a logistic regression model on ITT Population. The odds ratio for treatment difference and associated p-value and 95 percent CI were calculated. Up to Week 52
Secondary Number of Participants in Each Category of Accrued Duration of Remission Total accrued duration of remission, i.e., the accrued number of weeks where Birmingham Vasculitis Activity Score (BVAS) =0 plus prednisolone/prednisone dose <=7.5mg/day over the 52 week study treatment period was reported. BVAS is a validated, clinician-completed tool used for the comprehensive multisystem clinical assessment of disease activity in systemic vasculitis. The duration was categorized into zero, >0 to <12 weeks, 12 to <24 weeks, 24 to <36 weeks and >=36 weeks. Statistical analysis was performed on ITT Population and was based on a proportional odds regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region. The odds ratio for treatment difference and associated p-value and 95 percent CI were calculated. Up to Week 52
Secondary Number of Participants Who Are in Remission at 36 and 48 Weeks The number of participants who were in remission (i.e ., BVAS=0 and prednisolone /prednisone <=7.5mg/day) at both Weeks 36 and 48 of the study treatment period was reported. The statistical analysis was performed using a logistic regression model on ITT Population. The odds ratio for treatment difference and associated p-value and 95 percent CI were calculated. Week 36 and Week 48
Secondary 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 The number of participants who were in remission (i.e ., BVAS=0 and prednisolone /prednisone <=7.5mg/day) at both Weeks 36 and 48 of the study treatment period was reported. The statistical analysis was performed using a logistic regression model on ITT Population. The odds ratio for treatment difference and associated p-value and 95 percent CI were calculated. Up to Week 52
Secondary Number of Participants With Local and Systemic Adverse Events (AEs) An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs including systemic allergic and non-allergic reactions as well as local site injection-related reactions were counted throughout treatment phase and follow up phase. Systemic allergic reactions included Facial paralysis, flushing, hypersensitivity and rash pruritic. Injection related reactions were considered as systemic non-allergic reactions. Local site reactions included injection site bruising, erythema, pain and reaction. The analysis was performed on Safety Population which comprised of all participants who receive at least one dose of study treatment. Up to Week 52
Secondary 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 Blood samples were collected to evaluate change from Baseline in ALT, Alk.phosph., AST, creatinine kinase, GGT and lactate dehydro values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary Change From Baseline in Clinical Chemistry Parameters of Albumin and Protein Levels Blood samples were collected to evaluate change from Baseline in albumin and protein levels values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary Change From Baseline in Clinical Chemistry Parameters of Direct, Indirect and Total Bilirubin and Creatinine Levels Blood samples were collected to evaluate change from Baseline in direct, indirect and total bilirubin and creatinine values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary 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 Blood samples were collected to evaluate 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 values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. NA indicates that data were not available. Baseline and up to Week 60
Secondary Change From Baseline in Clinical Chemistry Parameter of Troponin Levels Blood samples were collected to evaluate change from Baseline in troponin values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary Change From Baseline in Hematology Parameters of Basophils, Eosinophil, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Levels Blood samples were collected to evaluate change from Baseline in basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelet values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary Change From Baseline in Hematology Parameters of Mean Corpuscle Hemoglobin Concentration (MCHC) and Hemoglobin Levels Blood samples were collected to evaluate change from Baseline in MCHC and hemoglobin values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary Change From Baseline in Hematology Parameters of Mean Corpuscle Volume (MCV) Levels Blood samples were collected to evaluate change from Baseline in MCV values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary Change From Baseline in Hematology Parameters of Mean Corpuscle Hemoglobin (MCH) Levels Blood samples were collected to evaluate change from Baseline in MCH values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary Change From Baseline in Hematology Parameters of Erythrocytes Levels Blood samples were collected to evaluate change from Baseline in erythrocytes values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary Number of Participants With Anti-Mepolizumab Antibodies Blood samples were collected for the determination of anti-Mepolizumab antibodies. Participants who showed presence of anti-Mepolizumab antibody were termed as 'positive' and those who did not have anti-Mepolizumab antibody in blood sample were termed as 'negative'. Participants who did not have a positive ADA assay prior to the first dose of investigational product were included in the analysis. Up to Week 60
Secondary Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Levels SBP and DBP were measured from Baseline throughout follow-up (till Week 60) before injection with the participant sitting, having rested in this position for at least 5 minutes before reading. The Baseline value was taken at Visit 2 and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline up to Week 60
Secondary Change From Baseline in Pulse Rate Pulse rate was measured from Baseline throughout follow-up (till Week 60) before injection with the participant sitting, having rested in this position for at least 5 minutes before reading. The Baseline value was taken at Visit 2 and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary Change From Baseline in Body Temperature Body temperature was measured from Baseline throughout follow-up (till Week 60). The Baseline value was taken at Visit 2 and change from Baseline was defined as post dose visit value minus Baseline value. The analysis was performed on Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. Baseline and up to Week 60
Secondary Mean Change From Baseline in QT Interval Corrected by Fridericia's Method (QTcF) and QT Interval Corrected by Bazett's Method (QTcB) Values Single measurements of 12-lead electrocardiogram (ECGs) were obtained after 5 minutes rest in a supine position at Baseline throughout the 52 weeks treatment period and 8 weeks follow-up period using an ECG machine. Mean change from Baseline in QTcF and QTcB values were measured. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Baseline and up to Week 60
Secondary Maximum Change From Baseline in QTcF and QTcB Values Single measurements of 12-lead ECGs were obtained after 5 minutes rest in a supine position at Baseline throughout the 52 weeks treatment period and 8 weeks follow-up period using an ECG machine. Maximum change from Baseline in QTcF and QTcB values were measured. Baseline and up to Week 60
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