Last updated: 07/17/2024 15:47:02
Efficacy and safety study of mepolizumab adjunctive therapy in subjects with severe uncontrolled refractory asthma
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: MEA115588 A randomised, double-blind, double-dummy, placebo-controlled, parallel-group, multi-centre study of the efficacy and safety of mepolizumab adjunctive therapy in subjects with severe uncontrolled refractory asthma
Trial description: This study will evaluate two dose regimens of mepolizumab [75mg intravenous (i.v.) or 100mg subcutaneous (SC) every 4 weeks] compared with placebo over a 32 week treatment period in subjects with severe refractory asthma with elevated blood eosinophils. Efficacy will be measured by a reduction in the frequency of asthma exacerbations. Additional efficacy assessments will include measurements of lung function, symptom scores, and quality of life. Safety will be assessed by clinical laboratory samples, ECGs, immunogenicity and adverse events.This study is intended to replicate the Phase IIb/III study MEA112997. Subjects in MEA115588, who meet all eligibility criteria at screening visit, will enter the run-in period. Those subjects that are not able/eligible to be randomised at the end of the 6 week run-in period will be deemed run-in failures. Subjects will remain on their current maintenance therapy throughout the run-in, double-blind treatment administration and follow-up periods. Subjects who meet the randomisation eligibility criteria will be randomised in a 1:1:1 ratio to receive one of the following treatments every 4 weeks for a total of 8 doses: Mepolizumab 75 miligram (mg) i.v. and placebo SC, or Mepolizumab 100 mg SC and placebo i.v. or Placebo i.v. and placebo SC.Subjects that receive all 8 doses of double-blind treatment, and meet the eligibility criteria for the Open-Label Extension (OLE) Study, will be offered the opportunity to participate in the OLE trial.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of clinically significant exacerbations of asthma per year
Timeframe: From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose
Secondary outcomes:
Number of clinically significant exacerbations requiring hospitalization (including intubation and admittance to an intensive care unit [ICU]) or ED visits per year
Timeframe: From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose
Number of clinically significant exacerbations requiring hospitalization (including intubation and admittance to an ICU) per year
Timeframe: From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose
Mean change from Baseline in clinic pre-bronchodilator forced expiratory volume in 1 second (FEV1) at Week 32
Timeframe: Baseline, Week 32
Mean change from Baseline in the St. George’s Respiratory Questionnaire total score at Week 32
Timeframe: Baseline, Week 32
Interventions:
Enrollment:
580
Primary completion date:
2014-18-01
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, Chanez P. Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma. N Engl J Med. 2014;371:1198-207.
Kim MK, Park HS, Park CS, Min SJ, Albers FC, Yancey SW, Mayer B, Kwon N.Efficacy and safety of mepolizumab in Korean patients with severe eosinophilic asthma from the DREAM and MENSA studies.Korean J Intern Med.2020;
DOI: 10.3904/kjim.2019.198
PMID: 32450626
Howarth P, Quirce S, Papi A, Israel E, Mallett S, Bates S, Yancey S, Albers F, Kwon N.Eosinophil-derived neurotoxin and clinical outcomes with mepolizumab in severe eosinophilic asthma.Allergy.2020;
DOI: 10.1111/all.14266
Nelsen L, Cockle S, Gunsoy N, Jones P, Albers F, Bradford E, Meullerova H.Impact of exacerbations on St Georges Respiratory Questionnaire score in patients with severe asthma: post hoc analyses of two clinical trials and an observational study .J Asthma.2019;
DOI: 10.1080/02770903.2019.1630640
PMID: 31251094
Medical condition
Asthma
Product
mepolizumab
Collaborators
Not applicable
Study date(s)
October 2012 to January 2014
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
12+ years
Accepts healthy volunteers
No
- Able to give written informed consent prior to participation in the study
- At least 12 years of age at visit 1 and a minimum weight of 45 kilogram (kg)
- Current smokers or former smokers with a smoking history of >=10 pack years
- Presence of a known pre-existing, clinically important lung condition other than asthma
Inclusion and exclusion criteria
Inclusion criteria:
- Able to give written informed consent prior to participation in the study
- At least 12 years of age at visit 1 and a minimum weight of 45 kilogram (kg)
- A well-documented requirement for regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS)
- Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months
- Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma
- At Visit 1, a pre-bronchodilator FEV1 <80% (for subjects >= 18 years of age), a pre-bronchodilator FEV1 <90% or FEV1:FVC ratio <0.8 (for subjects 12-17 years of age).
- Previously confirmed history of two or more exacerbations requiring treatment with systemic CS
- Male or Eligible Female (females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control)
- French subjects will be included only if either affiliated to or a beneficiary of a social security category.
Exclusion criteria:
- Current smokers or former smokers with a smoking history of >=10 pack years
- Presence of a known pre-existing, clinically important lung condition other than asthma
- A current malignancy or previous history of malignancy in less than 12 months
- Known, pre-existing, unstable liver disease cirrhosis and known biliary abnormalities
- Known, pre-existing severe or clinically significant cardiovascular disease
- known, pre-existing other concurrent clinically significant medical conditions that are uncontrolled with standard treatment
- Subjects with any eosinophilic diseases
- QTc(F) ≥450msec or QTc(F) ≥480 msec
- A history of alcohol/substance abuse
- Subject with known immunodeficiency
- Subjects who have received omalizumab within 130 days of Visit 1 or any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1
- Subjects who have received treatment with an investigational drug within the past 30 days or five terminal phase half-lives of the drug whichever is longer
- Subjects with allergy/intolerance to a monoclonal antibody or biologic.
- Subjects who are pregnant or breastfeeding
- Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations
- Previously participated in any study with mepolizumab and received investigational product (including placebo)
Trial location(s)
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21224
Status
Study Complete
Showing 1 - 6 of 126 Results
Study documents
Protocol
Available language(s): English
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2014-18-01
Actual study completion date
2014-18-01
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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