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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01691859

Enrollment

347

Registered

2012-09-25

Start date

2012-09-28

Completion date

2017-05-31

Last updated

2023-06-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

extension study, Severe refractory asthma, safety, SB-240563, mepolizumab, eosinophils

Brief summary

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.

Interventions

DRUGMepolizumab

100 mg of mepolizumab will be injected subcutaneously (SC) once every 4 weeks

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Who Experienced On-treatment Adverse Events (AE) and On-treatment Serious Adverse Events (SAE)	Baseline (Week 0) to Week 240	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.

Secondary

Measure	Time frame	Description
Mean Change From Baseline in QT Interval Corrected by Bazett's Method (QTc[B])	Baseline (Week 0) to Week 240	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.
Mean Change From Baseline in QT Interval Corrected by Fridericia's Method (QTc[F])	Baseline (Week 0) to Week 240	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.
Number of Participants With a Maximum Change From Baseline for QTc(F) and QTc(B)	Baseline (Week 0) to Week 240	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.
Number of Participants With Clinical Chemistry Data of Potential Clinical Concern	Baseline (Week 0) to Week 240	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.
Number of Participants With Hematology Data of Potential Clinical Concern	Baseline (Week 0) to Week 240	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.
Mean Change From Baseline in Vital Signs-Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure	Baseline (Week 0) to Week 240	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.
Mean Change From Baseline in Vital Signs-Sitting Pulse Rate	Baseline (Week 0) to Week 240	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.
Number of Participants Who Experienced On-treatment Systemic (i.e., Allergic/Immunoglobulin E [IgE]-Mediated and Non-allergic) and On-treatment Local Site Reactions	Baseline (Week 0) to Week 240	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.
Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score	Baseline (Week 0) to Week 240	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.
Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	Baseline (Week 0) to Week 240	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.
Number of Participants With Positive Anti-mepolizumab Binding Antibodies (ADA) and Neutralizing Antibodies (NAb)	Baseline (Week 0) to Week 240	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.
Number of Participants Who Withdrew Due to Lack of Efficacy	Baseline (Week 0) to Week 240	Lack of efficacy referred to failure of expected pharmacological action of Mepolizumab. Number of participants who withdrew due to lack of efficacy are presented.
Number of Participants Requiring Hospitalizations Due to Adverse Events Including Asthma Exacerbations	Baseline (Week 0) to Week 240	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.
Number of Participants Who Withdrew Due to AE	Baseline (Week 0) to Week 240	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.
Annualized Rate of On-treatment Exacerbations	Baseline (Week 0) to Week 240	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.

Countries

Argentina, Australia, Canada, Chile, France, Germany, Poland, Romania, Russia, South Korea, Ukraine, United Kingdom, United States

Participant flow

Recruitment details

This was a multi-center, open-label, long term safety study of mepolizumab in 347 asthmatic participants who participated in the MEA112997 trial and were found eligible for this study after screening and run in phase. The study was conducted at 65 centers in 13 countries from 28 Sep 2012 to 31 May 2017.

Pre-assignment details

A total of 362 participants were screened; 4 participants were screen failures (did not meet the inclusion/exclusion criteria); 11 participants were withdrawn during the run-in period (4 did not meet the continuation criteria, 4 withdrawal by participant and 3 following physician decision).

Participants by arm

Arm	Count
Mepolizumab 100 mg Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.	347
Total	347

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	19
Overall Study	Lack of Efficacy	11
Overall Study	Lost to Follow-up	5
Overall Study	Physician Decision	6
Overall Study	Product commercially available	221
Overall Study	Protocol Violation	4
Overall Study	Study closed/terminated	50
Overall Study	Withdrawal by Subject	31

Baseline characteristics

Characteristic	Mepolizumab 100 mg
Age, Continuous	52.2 Years STANDARD_DEVIATION 10.73
Race/Ethnicity, Customized African American/African Heritage	8 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	2 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	4 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	14 Participants
Race/Ethnicity, Customized Asian & Native Hawaiian or Other Pacific Islander	1 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	7 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	311 Participants
Sex: Female, Male Female	224 Participants
Sex: Female, Male Male	123 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	6 / 347
other Total, other adverse events	314 / 347
serious Total, serious adverse events	79 / 347

Outcome results

Primary

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.