MEA112997 Open-label Long Term Extension Safety Study of Mepolizumab in Asthmatic Subjects

Study Overview
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Brief Summary
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This is a multi-centre, open-label long term safety study of 100 milligrams (mg) mepolizumab administered subcutaneously (SC) in addition to standard of care in subjects who participated in the MEA112997 study. At each clinic visit, adverse events will be assessed and exacerbations will also be reviewed.

Official Title
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MEA115666: A Multi-centre, Open-label, Long Term Safety Study of Mepolizumab in Asthmatic Subjects Who Participated in the MEA112997 Trial

Conditions
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Asthma

Intervention / Treatment
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* Drug: Mepolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent. MEA112997 Study Participation: Received at least 2 doses of double-blind investigational product during the MEA112997 trial. MEA112997 Treatment Assignment: If the subject received mepolizumab, they must have had a positive risk: benefit ratio. Currently being treated with a controller medication and the subject has been on a controller medication for the past 12 weeks. Male or Eligible Female Subjects. To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control for the duration of the trial and for 4 months after the last study drug administration. Exclusion Criteria: Hypersensitivity related to mepolizumab. Clinically significant change in health status since completing participation in the MEA112997 trial. A current malignancy or previous history of cancer in remission for less than 12 months prior to screening. For those subjects who had a SAE in MEA112997 that was assessed as possibly related to mepolizumab by the investigator. Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation. Screening ECG which has a clinically significant abnormality. Received Xolair (omalizumab) within the past 130 days. Participated in a clinical trial within the past 30 days or have received investigational medication within five terminal half-lives of Screen Visit, whichever is longer. Current smokers.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mepolizumab<br>Subjects will receive 100 mg of mepolizumab (in 1ml polypropylene syringe) injected subcutaneously (SC) approximately every 4 weeks. | Drug: Mepolizumab<br>* 100 mg of mepolizumab will be injected subcutaneously (SC) once every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced On-treatment Adverse Events (AE) and On-treatment Serious Adverse Events (SAE) | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a medicinal product (MP), whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or all events of possible drug induced liver injury with hyperbilirubinemia. As Treated (AT) Population consisted of participants who received at least one dose of open label mepolizumab. On-treatment AEs and on-treatment SAEs are the events occurring on/after the first dose of open-label mepolizumab date and before/on last dose of mepolizumab + 28 days. | Baseline (Week 0) to Week 240 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced On-treatment Systemic (i.e., Allergic/Immunoglobulin E [IgE]-Mediated and Non-allergic) and On-treatment Local Site Reactions | Systemic and local site reactions following mepolizumab dosing as identified by the investigator and the number of participants who experienced systemic and/or local site reactions are presented. On-treatment AEs and on-treatment SAEs are the events occurring on/after the first dose of open-label mepolizumab date and before/on last dose of mepolizumab + 28 days. | Baseline (Week 0) to Week 240 | 
| Mean Change From Baseline in QT Interval Corrected by Bazett's Method (QTc[B]) | Twelve-lead ECGs were performed at Screening and every 24 weeks during the treatment period. ECG measurements were made after the participant had rested in the supine position for 5 minutes. Collection shortly after a meal or during sleep was avoided as QT prolongation can occur at these times. Baseline was the last available ECG prior to mepolizumab dosing. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Baseline (Week 0) to Week 240 | 
| Mean Change From Baseline in QT Interval Corrected by Fridericia's Method (QTc[F]) | Twelve-lead ECGs were performed at Screening and every 24 weeks during the treatment period. ECG measurements were made after the participant had rested in the supine position for 5 minutes. Collection shortly after a meal or during sleep was avoided as QT prolongation can occur at these times. Baseline was the last available ECG prior to mepolizumab dosing. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Baseline (Week 0) to Week 240 | 
| Number of Participants With a Maximum Change From Baseline for QTc(F) and QTc(B) | Twelve-lead ECGs were performed at Screening and every 24 weeks during the treatment period. ECG measurements were made after the participant had rested in the supine position for 5 minutes. Collection shortly after a meal or during sleep was avoided as QT prolongation can occur at these times. Baseline was the last available ECG prior to mepolizumab dosing. Change from Baseline was post-Baseline values minus Baseline values. Number of participants with a maximum change from Baseline for QTc(F) and QTc(B) at any time post Baseline are presented. Only those participants who provided ECG data at baseline and post-baseline were analyzed. | Baseline (Week 0) to Week 240 | 
| Number of Participants With Clinical Chemistry Data of Potential Clinical Concern | Clinical chemistry analytes with laboratory ranges defining values of potential clinical concern included sodium, potassium, calcium, phosphate, serum glucose and alanine aminotransferase. Number of participants with clinical chemistry abnormalities of potential clinical concern anytime post baseline are presented. Only those participants who provided lab data post-baseline were analyzed represented by n=X in the category titles. | Baseline (Week 0) to Week 240 | 
| Number of Participants With Hematology Data of Potential Clinical Concern | Hematology parameters with laboratory ranges defining values of potential clinical concern included hemoglobin, hematocrit, platelet count, white blood cell count. Number of participants with clinical hematology abnormalities of potential clinical concern anytime post baseline are presented, which only included participants with low hemoglobin values. Only those participants who provided lab data post-baseline were analyzed. | Baseline (Week 0) to Week 240 | 
| Mean Change From Baseline in Vital Signs-Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure | Vital signs included sitting pulse rate and sitting blood pressure (diastolic and systolic). Measurements were done pre injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Baseline (Week 0) to Week 240 | 
| Mean Change From Baseline in Vital Signs-Sitting Pulse Rate | Vital signs included sitting pulse rate and blood pressure (diastolic and systolic). Measurements were done pre injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Baseline (Week 0) to Week 240 | 
| Annualized Rate of On-treatment Exacerbations | Exacerbations were defined as worsening of asthma which required use of systemic corticosteroids and/or hospitalization and/or Emergency Department visits. Data is presented as mean which is exacerbation rate/year. Exacerbation data are performed using a negative binomial model with covariates of region, annualized rate of exacerbations in the interval between MEA112997 and MEA115666 (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable. | Baseline (Week 0) to Week 240 | 
| Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score | The ACQ-5 is a five-item questionnaire, which was developed as a measure of participant' asthma control that was completed by the participant. The five questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, and shortness of breath, wheeze). The ACQ consists of 5 questions that are scored on a 7 point scale from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ score was derived as mean of five questions: ACQ score = Question 1 (Q1)+Q2+Q3+Q4+Q5 divided by 5 where Q1, Q2,... Q5 are the scores of Q1, Q2, ..., Q5, respectively. The total score ranged from zero (no impairment/limitation) which indicated best condition to six (total impairment/ limitation) which indicated worst asthma. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Baseline (Week 0) to Week 240 | 
| Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | FEV1 is forced expiratory volume in the first second. The volume of air that can be forced out in one second after taking a deep breath, an important measure of pulmonary function. Forced expiratory volume (FEV) measures how much air a person can exhale during a forced breath. FEV1 was measured by clinic spirometry. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Baseline (Week 0) to Week 240 | 
| Number of Participants With Positive Anti-mepolizumab Binding Antibodies (ADA) and Neutralizing Antibodies (NAb) | Immunogenicity testing included two types of assays: a binding antibody assay (anti-drug antibody; ADA) and a neutralizing antibody (NAb) assay for participants who were tested positive in the ADA assay. Blood samples were collected for the determination of anti-mepolizumab antibodies, just prior to administration of mepolizumab. Samples that test positive for anti-mepolizumab antibodies were further tested for the presence of neutralizing antibody. Number of participants with positive highest value post-Baseline have been presented. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Baseline (Week 0) to Week 240 | 
| Number of Participants Who Withdrew Due to Lack of Efficacy | Lack of efficacy referred to failure of expected pharmacological action of Mepolizumab. Number of participants who withdrew due to lack of efficacy are presented. | Baseline (Week 0) to Week 240 | 
| Number of Participants Requiring Hospitalizations Due to Adverse Events Including Asthma Exacerbations | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or all events of possible drug induced liver injury with hyperbilirubinemia. Number of participants requiring hospitalization due to an on-treatment serious adverse event including asthma exacerbations are presented. On-treatment SAEs are the events occurring on/after the first dose of open-label mepolizumab date and before/on last dose of mepolizumab + 28 days. | Baseline (Week 0) to Week 240 | 
| Number of Participants Who Withdrew Due to AE | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or all events of possible drug induced liver injury with hyperbilirubinemia. Number of participants who withdrew due to AE are presented. | Baseline (Week 0) to Week 240 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extension study, Severe refractory asthma, safety, SB-240563, mepolizumab, eosinophils