Last updated: 07/17/2024 17:04:26
Efficacy and safety study of mepolizumab adjunctive therapy in participants with severe eosinophilic asthma on markers of asthma control
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre 24-week Study to Evaluate the Efficacy and Safety of Mepolizumab Adjunctive Therapy in Subjects with Severe Eosinophilic Asthma on Markers of Asthma Control
Trial 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Mean change from Baseline (BL) in St. George’s Respiratory Questionnaire (SGRQ) score at Week 24
Timeframe: Baseline and Week 24
Secondary outcomes:
Mean change from Baseline in clinic pre-bronchodilator Forced Expiratory Volume in one second (FEV1) at Week 24
Timeframe: Baseline and Week 24
Percentage of participants achieving a 4 point or greater reduction from Baseline in SGRQ score at Week 24
Timeframe: Baseline (Visit 2-latest pre-dose assessment) and Week 24
Mean change from Baseline in Asthma Control Questionnaire (ACQ-5) score at Week 24
Timeframe: Baseline and Week 24
Interventions:
Biological/vaccine: Mepolizumab
Drug: Placebo
Drug: SOC
Enrollment:
556
Observational study model:
Not applicable
Primary completion date:
2016-10-06
Time perspective:
Not applicable
Clinical publications:
Chupp GL, Bradford ES, Albers FC, Bratton DJ, Wang-Jairai J, Nelsen LM, Trevor JL, Magnan A, Brinke A. 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. Lancet Respir Med. 2017;5(5):90–400.
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)
December 2014 to June 2016
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
12+ years
Accepts healthy volunteers
No
- Age: At least 12 years of age at the time of signing the informed consent/assent (For those countries where local regulations permit enrolment of adults only, participant recruitment will be restricted to those who are >=18 years of age)
- Inhaled Corticosteroid: 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). For participants >=18 years old: ICS dose must be >=880 micrograms (mcg)/day fluticasone propionate (FP) (exactuator) or equivalent daily. For ICS/long-acting beta-2-agonist (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. For participants >=12 to <=17 years old: ICS dose must be >=440 mcg/day FP (ex-actuator) or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion
- Smoking history: Current smokers or former smokers with a smoking history of >=10 pack years (number of pack years = (number of cigarettes per day/20) x number of years smoked). A former smoker is defined as a participant who quit smoking at least 6 months prior to Visit 1.
- Concurrent Respiratory Disease: Presence of a known pre-existing, clinically important lung condition other than asthma. This includes current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
Inclusion and exclusion criteria
Inclusion criteria:
- Age: At least 12 years of age at the time of signing the informed consent/assent (For those countries where local regulations permit enrolment of adults only, participant recruitment will be restricted to those who are >=18 years of age)
- Inhaled Corticosteroid: 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). For participants >=18 years old: ICS dose must be >=880 micrograms (mcg)/day fluticasone propionate (FP) (exactuator) or equivalent daily. For ICS/long-acting beta-2-agonist (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. For participants >=12 to <=17 years old: ICS dose must be >=440 mcg/day FP (ex-actuator) or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion
- Controller Medication: 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 (e.g. LABA, leukotriene receptor antagonist [LTRA], or theophylline)
- Eosinophilic asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma as per Randomisation Criteria 1 and 2
- FEV1: Persistent airflow obstruction as indicated by : For participants >=18 years of age at visit 1, a pre-bronchodilator FEV1 <80% predicted (National Health and Nutrition Examination Survey [NHANES III]) recorded at Visit 1. For participants 12-17 years of age at Visit 1: A pre-bronchodilator FEV1 <90% predicted (NHANES III) recorded at Visit 1 OR FEV1:FVC ratio <0.8 recorded at Visit 1
- Exacerbation history: Previously confirmed history of two or more exacerbations requiring treatment with systemic Corticosteroid (CS) (intramuscular, intravenous, or oral), in the 12 months prior to visit 1, despite the use of high-dose inhaled corticosteroids (ICS). For participants receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold dose increase or greater.
- Gender: Male or Eligible Female. 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 listed in the protocol for the duration of the trial and for 4 months after the last study drug administration.
- Informed Consent/Assent: Able to give written informed consent/assent prior to participation in the core study, which will include the ability to comply with the requirements and restrictions listed in the consent/assent form and in this protocol. Participants must be able to read, comprehend, and write at a level sufficient to complete study related materials. Written informed consent must be obtained from ALL patients/legally authorized representative(s); for patients 12-17 years old, written informed assent must be obtained in addition to the legally authorized representative(s)’ consent.
- French participants: In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion criteria:
- Smoking history: Current smokers or former smokers with a smoking history of >=10 pack years (number of pack years = (number of cigarettes per day/20) x number of years smoked). A former smoker is defined as a participant who quit smoking at least 6 months prior to Visit 1.
- Concurrent Respiratory Disease: Presence of a known pre-existing, clinically important lung condition other than asthma. This includes current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
- Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Participants that had localized carcinoma of the skin which was resected for cure will not be excluded).
- Liver Disease: Known, pre-existing, unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
- Cardiovascular: Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to: (a) known ejection fraction of <30% OR (b) severe heart failure meeting New York Heart Association Class IV classification OR (c) hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III OR (d) angina diagnosed less than 3 months prior to Visit 1 or at Visit 1.
- Other Concurrent Medical Conditions: Participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
- Eosinophilic Diseases: Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis [EGPA]), or Eosinophilic Esophagitis. Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded.
- Electrocardiogram (ECG) Assessment: QT interval corrected for heart rate by Fridericia’s formula (QTc(F)) >=450 milliseconds (msec) or QTc(F) >=480 msec for participants with Bundle Branch Block at Visit 1.
- Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
- Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus [HIV]), other than that explained by the use of corticosteroids taken as therapy for asthma.
- Xolair: Participants who have received omalizumab (Xolair) within 130 days of Visit 1.
- Other Monoclonal Antibodies: Participants who have received any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
- Investigational Medications: Participants 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, prior to Visit 1 (this also includes investigational formulations of marketed products).
- Hypersensitivity: Participants with allergy/intolerance to a monoclonal antibody or biologic.
- Pregnancy: Participants who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required of all women of child bearing potential. This test will be performed at the time points specified in the Time and Events Schedule in protocol.
- Adherence: Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.
- Previous participation: Previously participated in any study with mepolizumab and received investigational product (including placebo)
Trial location(s)
Location
GSK Investigational Site
Aventura, Florida, United States, 33180
Status
Study Complete
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21236
Status
Study Complete
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35243
Status
Study Complete
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35294
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45231
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1121ABE
Status
Study Complete
Location
GSK Investigational Site
Concepcion del Uruguay, Entre Ríos, Argentina, 3260
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
Fresno, California, United States, 93720
Status
Study Complete
Location
GSK Investigational Site
Gastonia, North Carolina, United States, 28054
Status
Study Complete
Location
GSK Investigational Site
Hradec Kralove, Czech Republic, 500 05
Status
Study Complete
Location
GSK Investigational Site
Koblenz, Rheinland-Pfalz, Germany, 56068
Status
Study Complete
Location
GSK Investigational Site
Kralupy nad Vltavou, Czech Republic, 278 01
Status
Study Complete
Location
GSK Investigational Site
La Plata, Buenos Aires, Argentina, 1900
Status
Study Complete
Location
GSK Investigational Site
Long Beach, California, United States, 90808
Status
Study Complete
Location
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, 7600
Status
Study Complete
Location
GSK Investigational Site
New Haven, Connecticut, United States, 06520
Status
Study Complete
Location
GSK Investigational Site
Newport Beach, California, United States, 92663
Status
Study Complete
Location
GSK Investigational Site
Orangeburg, South Carolina, United States, 29118
Status
Study Complete
Location
GSK Investigational Site
Orlando, Florida, United States, 32825
Status
Study Complete
Location
GSK Investigational Site
Pozuelo de Alarcón/Madrid, Spain, 28223
Status
Study Complete
Location
GSK Investigational Site
Rapid City, South Dakota, United States, 57702
Status
Study Complete
Location
GSK Investigational Site
Reggio Emilia, Emilia-Romagna, Italy, 42100
Status
Study Complete
Location
GSK Investigational Site
Richmond, Virginia, United States, 23229
Status
Study Complete
Location
GSK Investigational Site
Riverside, California, United States, 92506
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
Salt Lake City, Utah, United States, 84132
Status
Study Complete
Location
GSK Investigational Site
San Martin de Porres, Lima, Peru, Lima 31
Status
Study Complete
Location
GSK Investigational Site
Schleswig, Schleswig-Holstein, Germany, 24837
Status
Study Complete
Location
GSK Investigational Site
St-Charles-Borromée, Ontario, Canada, J6E 2B4
Status
Study Complete
Location
GSK Investigational Site
Upland, California, United States, 91786
Status
Study Complete
Location
GSK Investigational Site
Vancouver, British Columbia, Canada, V5Z 1M9
Status
Study Complete
Location
GSK Investigational Site
Williamsburg, Virginia, United States, 23188
Status
Study Complete
Location
GSK Investigational Site
Witten, Nordrhein-Westfalen, Germany, 58452
Status
Study Complete
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
Completed
Actual primary completion date
2016-10-06
Actual study completion date
2016-10-06
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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