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NCT01691859

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

Completed Phase 3 Results posted Last updated 28 June 2023
What this trial tests

Phase 3 trial testing Mepolizumab in Asthma in 347 participants. Completed in 31 May 2017.

Timeline
28 September 2012
Primary endpoint
31 May 2017
31 May 2017

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment347
Start date28 September 2012
Primary completion31 May 2017
Estimated completion31 May 2017
Sites64 locations across France, Russia, Ukraine, Chile, United Kingdom, Germany, Poland, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Asthma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced On-treatment Adverse Events (AE) and On-treatment Serious Adverse Events (SAE) Primary · 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

AE
GroupValue95% CI
Mepolizumab 100 mg326
SAE
GroupValue95% CI
Mepolizumab 100 mg79
Number of Participants Who Experienced On-treatment Systemic (i.e., Allergic/Immunoglobulin E [IgE]-Mediated and Non-allergic) and On-treatment Local Site Reactions Secondary · 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.

Systemic reactions
GroupValue95% CI
Mepolizumab 100 mg9
Local site reactions
GroupValue95% CI
Mepolizumab 100 mg42
Mean Change From Baseline in QT Interval Corrected by Bazett's Method (QTc[B]) Secondary · 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.

Week 24, n=330
GroupValue95% CI
Mepolizumab 100 mg4.2± 18.57
Week 48, n=319
GroupValue95% CI
Mepolizumab 100 mg3.2± 17.19
Week 72, n=307
GroupValue95% CI
Mepolizumab 100 mg-0.5± 16.76
Week 96, n=293
GroupValue95% CI
Mepolizumab 100 mg1.3± 17.92
Week 124, n=292
GroupValue95% CI
Mepolizumab 100 mg1.5± 19.69
Week 148, n=275
GroupValue95% CI
Mepolizumab 100 mg1.6± 17.84
Week 176, n=201
GroupValue95% CI
Mepolizumab 100 mg0.6± 18.02
Week 200, n=149
GroupValue95% CI
Mepolizumab 100 mg3.3± 17.02
Mean Change From Baseline in QT Interval Corrected by Fridericia's Method (QTc[F]) Secondary · 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.

Week 24, n=330
GroupValue95% CI
Mepolizumab 100 mg5.1± 17.00
Week 48, n=319
GroupValue95% CI
Mepolizumab 100 mg4.1± 15.72
Week 72, n=307
GroupValue95% CI
Mepolizumab 100 mg0.2± 15.11
Week 96, n=293
GroupValue95% CI
Mepolizumab 100 mg2.2± 15.37
Week 124, n=292
GroupValue95% CI
Mepolizumab 100 mg3.2± 16.77
Week 148, n=275
GroupValue95% CI
Mepolizumab 100 mg2.9± 15.49
Week 176, n=201
GroupValue95% CI
Mepolizumab 100 mg2.0± 15.97
Week 200, n=149
GroupValue95% CI
Mepolizumab 100 mg4.3± 14.52
Number of Participants With a Maximum Change From Baseline for QTc(F) and QTc(B) Secondary · 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

QTc(F): < -60
GroupValue95% CI
Mepolizumab 100 mg0
QTc(F): >= -60 - < -30
GroupValue95% CI
Mepolizumab 100 mg1
QTc(F): >= -30 - < 0
GroupValue95% CI
Mepolizumab 100 mg31
QTc(F): >= 0 - < 30
GroupValue95% CI
Mepolizumab 100 mg252
QTc(F): >= 30 - < 60
GroupValue95% CI
Mepolizumab 100 mg55
QTc(F): >= 60
GroupValue95% CI
Mepolizumab 100 mg3
QTc(B): < -60
GroupValue95% CI
Mepolizumab 100 mg0
QTc(B): >= -60 - < -30
GroupValue95% CI
Mepolizumab 100 mg1
Number of Participants With Clinical Chemistry Data of Potential Clinical Concern Secondary · 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.

Potassium high, n=346
GroupValue95% CI
Mepolizumab 100 mg1
Serum glucose high, n=346
GroupValue95% CI
Mepolizumab 100 mg1
Serum glucose low, n=346
GroupValue95% CI
Mepolizumab 100 mg7
Number of Participants With Hematology Data of Potential Clinical Concern Secondary · 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.

GroupValue95% CI
Mepolizumab 100 mg1
Mean Change From Baseline in Vital Signs-Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure Secondary · 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.

Sitting Diastolic Blood Pressure: Week 4, n=346
GroupValue95% CI
Mepolizumab 100 mg-1.0± 8.71
Sitting Diastolic Blood Pressure: Week 8, n=345
GroupValue95% CI
Mepolizumab 100 mg-1.5± 8.85
Sitting Diastolic Blood Pressure: Week 12, n=342
GroupValue95% CI
Mepolizumab 100 mg-0.7± 9.67
Sitting Diastolic Blood Pressure: Week 16, n=341
GroupValue95% CI
Mepolizumab 100 mg-1.6± 9.27
Sitting Diastolic Blood Pressure: Week 20, n=338
GroupValue95% CI
Mepolizumab 100 mg-1.6± 9.17
Sitting Diastolic Blood Pressure: Week 24, n=336
GroupValue95% CI
Mepolizumab 100 mg-0.7± 9.27
Sitting Diastolic Blood Pressure: Week 28, n=332
GroupValue95% CI
Mepolizumab 100 mg-1.3± 8.90
Sitting Diastolic Blood Pressure: Week 32, n=333
GroupValue95% CI
Mepolizumab 100 mg-1.0± 9.62
Mean Change From Baseline in Vital Signs-Sitting Pulse Rate Secondary · 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.

Sitting Pulse Rate: Week 4, n=346
GroupValue95% CI
Mepolizumab 100 mg-0.3± 8.94
Sitting Pulse Rate: Week 8, n=345
GroupValue95% CI
Mepolizumab 100 mg1.0± 9.98
Sitting Pulse Rate: Week 12, n=342
GroupValue95% CI
Mepolizumab 100 mg0.0± 9.52
Sitting Pulse Rate: Week 16, n=341
GroupValue95% CI
Mepolizumab 100 mg-0.1± 10.08
Sitting Pulse Rate: Week 20, n=338
GroupValue95% CI
Mepolizumab 100 mg-0.3± 9.44
Sitting Pulse Rate: Week 24, n=337
GroupValue95% CI
Mepolizumab 100 mg-1.6± 9.83
Sitting Pulse Rate: Week 28, n=332
GroupValue95% CI
Mepolizumab 100 mg-0.2± 9.58
Sitting Pulse Rate: Week 32, n=333
GroupValue95% CI
Mepolizumab 100 mg-0.2± 9.74
Annualized Rate of On-treatment Exacerbations Secondary · 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.

GroupValue95% CI
Mepolizumab 100 mg0.680.60 – 0.78
Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Secondary · 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, ...

Week 12, n=341
GroupValue95% CI
Mepolizumab 100 mg-0.47± 0.991
Week 24, n=335
GroupValue95% CI
Mepolizumab 100 mg-0.55± 1.037
Week 36, n=327
GroupValue95% CI
Mepolizumab 100 mg-0.56± 1.088
Week 48, n=324
GroupValue95% CI
Mepolizumab 100 mg-0.55± 1.098
Week 60, n=317
GroupValue95% CI
Mepolizumab 100 mg-0.58± 1.126
Week 72, n=311
GroupValue95% CI
Mepolizumab 100 mg-0.51± 1.054
Week 84, n=308
GroupValue95% CI
Mepolizumab 100 mg-0.54± 1.090
Week 96, n=301
GroupValue95% CI
Mepolizumab 100 mg-0.44± 1.171
Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) Secondary · 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.

Week 12, n=340
GroupValue95% CI
Mepolizumab 100 mg124± 346.9
Week 24, n=334
GroupValue95% CI
Mepolizumab 100 mg144± 335.0
Week 48, n=325
GroupValue95% CI
Mepolizumab 100 mg98± 395.2
Week 72, n=312
GroupValue95% CI
Mepolizumab 100 mg91± 405.5
Week 96, n=301
GroupValue95% CI
Mepolizumab 100 mg51± 385.8
Week 124, n=292
GroupValue95% CI
Mepolizumab 100 mg85± 395.5
Week 148, n=281
GroupValue95% CI
Mepolizumab 100 mg17± 370.2
Week 176, n=210
GroupValue95% CI
Mepolizumab 100 mg45± 352.2

Adverse events — posted to ClinicalTrials.gov

Time frame: The on-treatment AEs and on-treatment SAEs are the events which happened on/after the first dose of open label mepolizumab date and before/on last dose of mepolizumab date + 28 days (up to 240 weeks). Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Mepolizumab
Serious: 79/347 (23%)
Deaths: 6/347

Serious adverse events (87 terms)

ReactionSystemMepolizumab
AsthmaRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
CellulitisInfections and infestations
Respiratory tract infectionInfections and infestations
BursitisMusculoskeletal and connective tissue disorders
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders
EpilepsyNervous system disorders
SciaticaNervous system disorders
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
CholelithiasisHepatobiliary disorders
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
Respiratory arrestRespiratory, thoracic and mediastinal disorders
Sleep apnoea syndromeRespiratory, thoracic and mediastinal disorders
Status asthmaticusRespiratory, thoracic and mediastinal disorders
Abscess limbInfections and infestations
Anal abscessInfections and infestations
GastroenteritisInfections and infestations
Herpes zosterInfections and infestations
InfluenzaInfections and infestations
Lower respiratory tract infectionInfections and infestations
MyelitisInfections and infestations
Postoperative wound infectionInfections and infestations
PyelonephritisInfections and infestations
Staphylococcal infectionInfections and infestations
Streptococcal infectionInfections and infestations
Other adverse events (53 terms — click to expand)

ReactionSystemMepolizumab
Viral upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
Upper respiratory tract infectionInfections and infestations
BronchitisInfections and infestations
AsthmaRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
SinusitisInfections and infestations
InfluenzaInfections and infestations
Injection site reactionGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Respiratory tract infectionInfections and infestations
Rhinitis allergicRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
Lower respiratory tract infectionInfections and infestations
GastroenteritisInfections and infestations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
PharyngitisInfections and infestations
Urinary tract infectionInfections and infestations
RhinitisInfections and infestations
DizzinessNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
ToothacheGastrointestinal disorders
Respiratory tract infection viralInfections and infestations
OsteoarthritisMusculoskeletal and connective tissue disorders
Viral infectionInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
SciaticaNervous system disorders
Ear infectionInfections and infestations
Abdominal pain upperGastrointestinal disorders
LacerationInjury, poisoning and procedural complications
Acute sinusitisInfections and infestations
Musculoskeletal painMusculoskeletal and connective tissue disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
CataractEye disorders
CystitisInfections and infestations
NasopharyngitisInfections and infestations

Most-reported serious reactions: Asthma, Pneumonia, Cellulitis, Respiratory tract infection, Bursitis, Intervertebral disc protrusion, Epilepsy, Sciatica.

Data from ClinicalTrials.gov NCT01691859 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma.
    Khatri S, Moore W, Gibson PG, Leigh R, et al · · 2019 · cited 204× · PMID 30359681 · DOI 10.1016/j.jaci.2018.09.033
  2. Anti-IL5 therapies for asthma.
    Farne HA, Wilson A, Powell C, Bax L, et al · · 2017 · cited 190× · PMID 28933516 · DOI 10.1002/14651858.cd010834.pub3
  3. Stopping <i>versus</i> continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study).
    Moore WC, Kornmann O, Humbert M, Poirier C, et al · · 2022 · cited 83× · PMID 34172470 · DOI 10.1183/13993003.00396-2021
  4. From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases.
    Pavord ID, Bel EH, Bourdin A, Chan R, et al · · 2022 · cited 61× · PMID 34402066 · DOI 10.1111/all.15056
  5. Eosinophilic Asthma: Pathophysiology and Therapeutic Horizons.
    Hussain M, Liu G. · · 2024 · cited 60× · PMID 38474348 · DOI 10.3390/cells13050384
  6. Severe Asthma and Biological Therapy: When, Which, and for Whom.
    Rogliani P, Calzetta L, Matera MG, Laitano R, et al · · 2020 · cited 56× · PMID 32048241 · DOI 10.1007/s41030-019-00109-1
  7. Anti-IL-5 therapies for asthma.
    Farne HA, Wilson A, Milan S, Banchoff E, et al · · 2022 · cited 37× · PMID 35838542 · DOI 10.1002/14651858.cd010834.pub4
  8. Proinflammatory Cytokines in Chronic Respiratory Diseases and Their Management.
    Chavda VP, Bezbaruah R, Ahmed N, Alom S, et al · · 2025 · cited 14× · PMID 40136649 · DOI 10.3390/cells14060400

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