Last updated: 07/17/2024 17:07:34
A phase 3a, repeat dose, open-label, long-term safety study of mepolizumab in asthmatic subjects
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Multi-Centre, Open-Label, Study of Mepolizumab in a Subset of Subjects with a History of Life Threatening/Seriously Debilitating Asthma Who Participated in the MEA115661 Trial
Trial description: This is a multi-center, open-label, long-term study of subcutaneously (SC) administered mepolizumab 100mg in addition to standard of care (SOC), in subjects with severe eosinophilic asthma. This study will enroll a subset of subjects from Study MEA115661 who have demonstrated clear benefit from therapy and who without continuation of mepolizumab therapy are individuals at greatest risk of serious deterioration of their health status. In order to target individuals at greatest risk for serious deterioration of their health status, only subjects from the MEA115661 study with a history of life-threatening or seriously debilitating asthma, will be allowed to participate. Subjects meeting all of the eligibility criteria for the study will be offered the opportunity to consent for this study of up to 128 weeks in length (including the Follow-Up Visit). This study will give opportunity to extend the collection of clinical data for long-term use and further assess the sustainability of efficacy in a population likely to experience significant loss of asthma control and the need for higher doses of systemic steroids if returned to SOC only.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
Annualized rate of on-treatment exacerbations per year
Timeframe: Baseline (Week 0) to Week 172
Number of participants with any on-treatment adverse event (AE) or on-treatment serious AE (SAE)
Timeframe: Baseline (Week 0) to Week 172
Secondary outcomes:
Mean change from Baseline in asthma control questionnaire (ACQ)-5 on-treatment score
Timeframe: Baseline (Week 0) to Week 168
Mean change from Baseline in on-treatment clinic pre-bronchodilator FEV1
Timeframe: Baseline (Week 0) to Week 168
Number of participants withdrawn from the study due to lack of efficacy and adverse events
Timeframe: Baseline (Week 0) to Week 172
Number of participants hospitalized due to adverse events including asthma exacerbations
Timeframe: Baseline (Week 0) to Week 172
Number of participants with AEs including both systemic (allergic and non-allergic) and local site reactions
Timeframe: Baseline (Week 0) to Week 172
Mean change from Baseline in QT interval corrected by Bazett's method (QTcB) and QT interval corrected by Fridericia's method (QTcF) values for 12-lead electrocardiogram (ECG)
Timeframe: Baseline (Week 0) to Week 172
Number of participants with maximum change from Baseline in QTcB and QTcF interval for ECG assessed at any time post Baseline
Timeframe: Baseline (Week 0) to Week 172
Change from Baseline in systolic blood pressure and diastolic blood pressure
Timeframe: Baseline (Week 0) to Week 168
Change from Baseline in pulse rate
Timeframe: Baseline (Week 0) to Week 168
Number of participants with positive anti-mepolizumab binding antibodies (ADA) and neutralizing antibodies (NAb)
Timeframe: Baseline (Week 0) to Week 172
Number of participants with Potential Clinical Importance values for change from Baseline relative to the reference range for clinical chemistry parameters at any time post-Baseline
Timeframe: Baseline (Week 0) to Week 172
Number of participants with Potential Clinical Importance values for change from Baseline relative to the reference range for hematology parameters at any time post-Baseline
Timeframe: Baseline (Week 0) to Week 172
Interventions:
Enrollment:
339
Primary completion date:
2017-05-10
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Khurana S, Brusselle G, Bel E, Fitzgerald M, Masoli M, Korn S, Kato M, Albers F, Bradford E, Gilson M, Price R, Humbert M. Long-Term Safety and Clinical Benefit of Mepolizumab in Patients with the Most Severe Eosinophilic Asthma: The COSMEX Study. Clin Ther. 2019;41(10):2041-2056.e5
DOI: 10.1016/j.clinthera.2019.07.007
PMID: 31447130
Medical condition
Asthma
Product
mepolizumab
Collaborators
Not applicable
Study date(s)
May 2014 to October 2017
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
12+ years
Accepts healthy volunteers
No
- Inclusion Criteria:
- Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent.
Inclusion and exclusion criteria
Inclusion criteria:
- Inclusion Criteria:
- Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent.
- Male or Eligible Female Subjects: To be eligible for the study, females of child-bearing potential must commit to consistent and correct use of an acceptable method of birth control and for 4 months after the last study drug administration. A urine pregnancy test is required of all females of childbearing potential at the initial Baseline Visit (Visit 1).
- French Subjects Only: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
- MEA115661 Participation: Subjects must have completed Visit 14 of MEA115661.
- Current Anti-Asthma Therapy: The subject’s asthma has been treated with an ICS controller medication for the last 8 months with fluticasone propionate (FP) >=500 mcg/day (or equivalent).
- Disease Severity: Subjects must be assessed as having life-threatening /serious debilitating asthma in order to enroll, as defined by the following: Subjects enrolled in MEA115588 must meet one of the following criteria: a) Subject has a history of at least one intubation during their lifetime; b) >=3 asthma exacerbations in the 12 months prior to screening for MEA115588; c) >=1 or more hospitalization for asthma exacerbation in the 12 months prior to screening for MEA115588. Subjects enrolled in MEA115575 must meet one of the following criteria: d) Subject has a history of at least one intubation during their lifetime; e) Their optimized dose at randomization in MEA115575 was >=10mg of prednisone; f) >=1 or more hospitalization for asthma exacerbation in the 12 months prior to screening for MEA115575.
- Clinical Benefit: Subjects must have experienced documented clinical benefit to enroll. Subjects must meet the following criteria demonstrating clinical benefit: Subjects enrolled in MEA115588 who received mepolizumab must meet all of the following criteria: a) Subject must have had a reduction in their exacerbation frequency by >=50% during MEA115588. The baseline for comparison is the total number of exacerbations reported in the 12 months prior to screening for MEA115588. b) The investigator response on the “Clinician-Rated Response to Therapy” questionnaire at Visit 10 was either: mildly improved, moderately improved or significantly improved. Subjects enrolled in MEA115588 who received placebo must meet all of the following criteria: c) Subject must have had a reduction in their exacerbation frequency by >=50% during the first 8 months of MEA115661. The baseline for comparison is the total number of exacerbations reported in the 12 months prior to screening for MEA115588; d) The investigator confirms that the subject demonstrated improvement during MEA115661. Subjects enrolled in MEA115575 who received mepolizumab must meet all of the following criteria: e) Subject must have reduced their oral corticosteroid dose by >=50% during MEA115575. The baseline for comparison is the subject’s optimized oral corticosteroid (OCS) dose at randomization in MEA115575; f) The investigator response on the “Clinician-Rated Response to Therapy” questionnaire at Visit 9 was either: mildly improved, moderately improved or significantly improved. Subjects enrolled in MEA115575 who received placebo must meet all of the following criteria: g) Subject must have reduced their oral corticosteroid dose at randomization by >=50% in the first 6 months of MEA115661. The baseline for comparison is the subject’s optimized OCS dose at randomization in MEA115575; h) The investigator confirms that the subject demonstrated improvement during MEA115661. Exclusion Criteria
- Health Status: Clinically significant change in health status during MEA115661 which in the opinion of the investigator would make the subject unsuitable for participation in this long-term study.
- Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnanDeart during the time of study participation.
- Exacerbation History: Subjects who received placebo in MEA115588 and had NO exacerbations during the study.
- Oral Corticosteroid Use: Subjects who received placebo in MEA115575 and were able to discontinue oral corticosteroid therapy by the end of the study.
- Smoking Status: Current smokers
- Previous Significant Protocol Deviation: Subjects who were excluded from the per protocol analysis due to significant protocol deviations in either study MEA115575 or MEA115588.
- Electrocardiogram (ECG) Assessment: A clinically significant ECG abnormality at the exit visit of MEA115661, as determined by the investigator.
Trial location(s)
Location
GSK Investigational Site
Anyang-Si Gyeonggi-do, South Korea, 431-070
Status
Study Complete
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21224
Status
Study Complete
Location
GSK Investigational Site
Bedford Park, South Australia, Australia, 5042
Status
Study Complete
Location
GSK Investigational Site
Bucheon city, Gyenggi-do, South Korea, 420-767
Status
Study Complete
Location
GSK Investigational Site
Buenos Aires, Buenos Aires, Argentina, C1424BSF
Status
Study Complete
Location
GSK Investigational Site
Cheongju, Chungcheongbuk-do, South Korea, 361-711
Status
Study Complete
Location
GSK Investigational Site
Denver, Colorado, United States, 80206
Status
Study Complete
Location
GSK Investigational Site
Durham, North Carolina, United States, 27705
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30173
Status
Study Complete
Location
GSK Investigational Site
Hershey, Pennsylvania, United States, 17033
Status
Study Complete
Location
GSK Investigational Site
Leicester, Leicestershire, United Kingdom, LE3 9QP
Status
Study Complete
Location
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23552
Status
Study Complete
Location
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
Status
Study Complete
Location
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, 7600
Status
Study Complete
Location
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Status
Study Complete
Location
GSK Investigational Site
New Haven, Connecticut, United States, 06510
Status
Study Complete
Location
GSK Investigational Site
New Lambton, New South Wales, Australia, 2305
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10029
Status
Study Complete
Location
GSK Investigational Site
Newport Beach, California, United States, 92663
Status
Study Complete
Location
GSK Investigational Site
Pietra Ligure (SV), Liguria, Italy, 17027
Status
Study Complete
Location
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
Status
Study Complete
Location
GSK Investigational Site
Pozuelo de Alarcón/Madrid, Spain, 28223
Status
Study Complete
Location
GSK Investigational Site
Rancagua, Reg Del Libert Bern Ohiggins, Chile, 2843099
Status
Study Complete
Location
GSK Investigational Site
Riverside, California, United States, 92506-0174
Status
Study Complete
Location
GSK Investigational Site
Rochester, Minnesota, United States, 55905
Status
Study Complete
Location
GSK Investigational Site
Rochester, New York, United States, 14642
Status
Study Complete
Location
GSK Investigational Site
Rolling Hills Estates, California, United States, 90274
Status
Study Complete
Location
GSK Investigational Site
Rosario, Santa Fe, Argentina, S2000DBS
Status
Study Complete
Location
GSK Investigational Site
Ruedersdorf, Brandenburg, Germany, 15562
Status
Study Complete
Location
GSK Investigational Site
Salt Lake City, Utah, United States, 84112
Status
Study Complete
Location
GSK Investigational Site
St-Charles-Borromée, Ontario, Canada, J6E 2B4
Status
Study Complete
Location
GSK Investigational Site
Suwon-si, Gyeonggi-do, South Korea, 443-380
Status
Study Complete
Location
GSK Investigational Site
Vancouver, British Columbia, Canada, V5Z 1M9
Status
Study Complete
Location
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27103
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
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
2017-05-10
Actual study completion date
2017-05-10
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
Additional information
Not applicable
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