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NCT02281318

Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants With Severe Eosinophilic Asthma on Markers of Asthma Control

Completed Phase 3 Results posted Last updated 6 August 2018
What this trial tests

Phase 3 trial testing Mepolizumab in Asthma in 556 participants. Completed in 10 June 2016.

Timeline
11 December 2014
Primary endpoint
10 June 2016
10 June 2016

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment556
Start date11 December 2014
Primary completion10 June 2016
Estimated completion10 June 2016
Sites144 locations across Italy, Netherlands, Russia, Belgium, Estonia, Bulgaria, United States, France

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

12 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.

Mean Change From Baseline (BL) in St. George's Respiratory Questionnaire (SGRQ) Score at Week 24 Primary · Baseline and Week 24

SGRQ consisted of 50 questions (scored from 0 to 100 where 0 indicates best and 100 indicates worst health) designed to measure Quality of Life in par. with diseases of airway obstruction, measuring symptoms, impact, and activity. Questions were completed by the par. with a recall over the past 4 weeks. SGRQ Total Score was calculated by summing the pre-assigned weights of answers, dividing by the sum of the maximum weights for items in SGRQ and multiplying by 100 to get a %. Change from BL in SGRQ was calculated as value at Week 24 minus value at BL for each par. and was analyzed using mixed

GroupValue95% CI
Placebo-7.9± 1.01
Mepolizumab 100 mg-15.6± 1.00
Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Week 24 Secondary · Baseline and Week 24

FEV1 is the volume of air that can be forced out in one second after taking a deep breath. The change from Baseline in pre-bronchodilator FEV1 was calculated as the value at Week 24 minus the value at Baseline for each subject and was analyzed using a mixed model repeated measures adjusting for Baseline absolute pre-bronchodilator FEV1, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study and visit, plus interaction terms for visit by Baseline and visit by treatment group.

GroupValue95% CI
Placebo56± 26.2
Mepolizumab 100 mg176± 26.1
Percentage of Participants Achieving a 4 Point or Greater Reduction From Baseline in SGRQ Score at Week 24 Secondary · Baseline (Visit 2-latest pre-dose assessment) and Week 24

The percentage of participants achieving a 4 point or greater reduction from Baseline in SGRQ (scored from 0-100 with lower scores indicating better outcome) at Week 24 was compared between treatment groups using a logistic regression model with covariates of Baseline value, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study (as an ordinal variable) and Baseline % predicted FEV1.

GroupValue95% CI
Placebo55
Mepolizumab 100 mg73
Mean Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 24 Secondary · Baseline and Week 24

The ACQ-5 is a five-item questionnaire, designed to be self-completed by the participants. ACQ-5 score is the mean score of 5 questions, each assessed on a 0-6 point scale to give a mean ranging between 0-6 with lower scores indicating better outcome. The five questions inquired about the frequency and/or severity of symptoms over the previous week. The response options for all these questions consisted of a zero (no impairment/limitation) to six (total impairment/limitation) scale. The mean change from Baseline was calculated as the value at Week 24 minus the Baseline value for each participa

GroupValue95% CI
Placebo-0.40± 0.064
Mepolizumab 100 mg-0.80± 0.064

Adverse events — posted to ClinicalTrials.gov

Time frame: All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24).. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 23/278 (8%)
Deaths:
Mepolizumab 100 mg SC
Serious: 15/273 (5%)
Deaths:

Serious adverse events (40 terms)

ReactionSystemPlaceboMepolizumab 100 mg SC
AsthmaRespiratory, thoracic and mediastinal disorders
Post procedural complicationInjury, poisoning and procedural complications
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Nasal polypsRespiratory, thoracic and mediastinal disorders
AppendicitisInfections and infestations
Bronchitis bacterialInfections and infestations
Catheter site infectionInfections and infestations
CellulitisInfections and infestations
Gastroenteritis rotavirusInfections and infestations
Hemophilus infectionInfections and infestations
LaryngitisInfections and infestations
Localized infectionInfections and infestations
Lung infectionInfections and infestations
SinusitisInfections and infestations
Staphylococcal bacteremiaInfections and infestations
Staphylococcal infectionInfections and infestations
Clavicle fractureInjury, poisoning and procedural complications
Fibula fractureInjury, poisoning and procedural complications
Meniscus injuryInjury, poisoning and procedural complications
Tibia fractureInjury, poisoning and procedural complications
HypertensionVascular disorders
HypotensionVascular disorders
Subclavian vein thrombosisVascular disorders
VasculitisVascular disorders
Myocardial ischemiaCardiac disorders
Other adverse events (13 terms — click to expand)

ReactionSystemPlaceboMepolizumab 100 mg SC
HeadacheNervous system disorders
NasopharyngitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Upper respiratory tract infectionInfections and infestations
Nasal congestionRespiratory, thoracic and mediastinal disorders
SinusitisInfections and infestations
BronchitisInfections and infestations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
RhinitisInfections and infestations
Muscle spasmsMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders

Most-reported serious reactions: Asthma, Post procedural complication, Acute respiratory failure, Nasal polyps, Appendicitis, Bronchitis bacterial, Catheter site infection, Cellulitis.

Data from ClinicalTrials.gov NCT02281318 adverse events section.

Sponsor's own description

This is a multi-centre, placebo-controlled, double-blind, parallel-group study to evaluate the efficacy and safety of mepolizumab adjunctive therapy in participants with severe eosinophilic asthma on markers of asthma control. The overall intent of the current study is to more fully explore the impact of mepolizumab on health-related quality of life (HR-QoL) and other measures of asthma control, including lung function. Participants who meet the predefined criteria will be randomised to receive either mepolizumab or placebo in addition to standard of care asthma treatment. Approximately 780 participants with severe eosinophilic asthma will be screened to ensure the randomisation of 544 participants (272 participants per treatment group) into the study.

Publications & conference data

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

  1. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial.
    Chupp GL, Bradford ES, Albers FC, Bratton DJ, et al · · 2017 · cited 427× · PMID 28395936 · DOI 10.1016/s2213-2600(17)30125-x
  2. The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma.
    Chapman KR, Albers FC, Chipps B, Muñoz X, et al · · 2019 · cited 113× · PMID 31049972 · DOI 10.1111/all.13850
  3. Real-world mepolizumab in the prospective severe asthma REALITI-A study: initial analysis.
    Harrison T, Canonica GW, Chupp G, Lee J, et al · · 2020 · cited 101× · PMID 32817259 · DOI 10.1183/13993003.00151-2020
  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. Baseline blood eosinophil count as a predictor of treatment response to the licensed dose of mepolizumab in severe eosinophilic asthma.
    Albers FC, Licskai C, Chanez P, Bratton DJ, et al · · 2019 · cited 48× · PMID 31751853 · DOI 10.1016/j.rmed.2019.105806
  7. Mepolizumab reduces exacerbations in patients with severe eosinophilic asthma, irrespective of body weight/body mass index: meta-analysis of MENSA and MUSCA.
    Albers FC, Papi A, Taillé C, Bratton DJ, et al · · 2019 · cited 39× · PMID 31362741 · DOI 10.1186/s12931-019-1134-7
  8. Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions.
    Gibson PG, Prazma CM, Chupp GL, Bradford ES, et al · · 2021 · cited 37× · PMID 34098955 · DOI 10.1186/s12931-021-01746-4

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