Last updated: 11/07/2018 09:38:23
Mepolizumab Steroid-Sparing Study in Subjects with Severe Refractory Asthma
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: MEA115575: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study of Mepolizumab Adjunctive Therapy to Reduce Steroid Use in Subjects with Severe Refractory Asthma
Trial description: This is a randomised, double-blind, placebo-controlled, parallel-group, multicenter study of mepolizumab in comparison with placebo in reducing Oral Corticosteroid (OCS) use in subjects with severe refractory asthma. The study consists of four phases, OCS Optimisation Phase (Week -8 to Week 0), and the double-blind treatment period divided into an Induction Phase (Week 0 to Week 4), OCS Reduction Phase (Week 5 upto Week 20) followed by Maintenance Phase (Week 20 to Week 24). During the Optimisation Phase the investigator will adjust the OCS (prednisone/prednisolone) dose according to the Optimisation titration schedule based on a review of Asthma Control Questionnaire (ACQ)-5 score and exacerbation. In the Induction Phase subjects will be randomized 1:1 (approximately 60 per arm) to receive either mepolizumab (100 mg) administered subcutaneously (SC) or placebo every 4 weeks in addition to their existing maintenance asthma therapy with the lowest dose of OCS from Optimisation Phase. The Induction Phase will allow sufficient time for those subjects randomised to the mepolizumab arm to achieve a decrease in the eosinophilic inflammation prior to the reduction in OCS. During the Reduction Phase, subjects will continue receiving 100 mg mepolizumab/placebo every 4 weeks and the OCS dose reduction will be done every 4 weeks using the reduction titration schedule based on a review of eDiary parameters recorded by the subject, the subjects’ exacerbation history, and a review of the signs and symptoms of adrenal insufficiency. In the Maintenance Phase subjects will be maintained without any further OCS dose adjustment. Subjects who complete the 24 week double-blind period and meet the eligibility criteria, will be offered the opportunity to participate in an open label extension (OLE) study otherwise they will return for a Follow-up Visit 12 weeks after their last dose of double blind study treatment. At each clinic visit, adverse events, safety labs, spirometery parameters and exacerbations will be assessed. The pharmacokinetic samples will be collected in the beginning of the treatment, prior to last dose, at the end of study (exit visit) and the follow up.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of participants with the indicated percent reduction from Baseline in oral corticosteroid (OCS) dose during Weeks 20 to 24 while maintaining asthma control
Timeframe: Baseline; Weeks 20 to 24
Secondary outcomes:
Number of participants who achieved a reduction of >=50% in their daily oral corticosteroid (OCS) dose compared with Baseline dose, during weeks 20 to 24 while maintaining asthma control
Timeframe: Baseline; Weeks 20 to 24
Number of participants who achieved a reduction of their daily OCS dose to <=5.0 mg during weeks 20 to 24 while maintaining asthma control
Timeframe: Weeks 20 to 24
Number of participants who achieved a total reduction of OCS dose during weeks 20 to 24 while maintaining asthma control
Timeframe: Weeks 20 to 24
Median percentage change from Baseline in daily OCS dose during weeks 20 to 24 while maintaining asthma control
Timeframe: Baseline; Weeks 20 to 24
Interventions:
Drug: Mepolizumab
Drug: Placebo
Drug: OCS (prednisone/prednisolone)
Enrollment:
135
Observational study model:
Not applicable
Primary completion date:
2013-12-12
Time perspective:
Not applicable
Clinical publications:
Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID, for the SIRIUS Investigators. Oral corticosteroid-sparing effect of mepolizumab in severe eosinophilic asthma. N Engl J Med. 2014;371:1189-97.
Medical condition
Asthma
Product
mepolizumab
Collaborators
Not applicable
Study date(s)
October 2012 to December 2013
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
12+ years
Accepts healthy volunteers
No
- Informed Consent and Study Compliance: Subjects must be able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form.
- Systemic Corticosteroids: Requirement for regular treatment with maintenance systemic corticosteroids in the 6 months prior to Visit 1 and using a stable oral corticosteroid dose for 4 weeks prior to Visit 1. Subjects must be taking 5.0 to 35 mg/day of prednisone or equivalent at Visit 1 and must agree to switch to study required prednisone/prednisolone as their oral corticosteroid and use it per protocol for the duration of the study.
- Smoking history: Current smokers or former smokers with a smoking history of >=10 pack years.
- Concurrent Respiratory Disease: Presence of a clinically important lung condition other than asthma.
Inclusion and exclusion criteria
Inclusion criteria:
- Informed Consent and Study Compliance: Subjects must be able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form.
- Systemic Corticosteroids: Requirement for regular treatment with maintenance systemic corticosteroids in the 6 months prior to Visit 1 and using a stable oral corticosteroid dose for 4 weeks prior to Visit 1. Subjects must be taking 5.0 to 35 mg/day of prednisone or equivalent at Visit 1 and must agree to switch to study required prednisone/prednisolone as their oral corticosteroid and use it per protocol for the duration of the study.
- Inhaled Corticosteroids: Requirement for regular treatment with high dose inhaled corticosteroid in the 6 months prior to Visit 1. For 18 years of age and older: inhaled corticosteroid (ICS) dose must be >=880 microgram (µg)/day fluticasone propionate (FP) (ex-actuator) or equivalent daily. For ICS/ long acting beta2 agonist (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. For ages 12 to 17: ICS dose must be >=440 μg/day FP (ex-actuator) or equivalent daily.
- Controller Medication: Current treatment with an additional controller medication for at least 3 months OR documentation of having used and failed an additional controller medication for at least 3 successive months during the prior 12 months [e.g., LABA, leukotriene receptor antagonist (LTRA), or theophylline].
- Eosinophilic Asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma.
- FEV1: Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 <80% predicted.
- Asthma: Evidence of asthma indicated by airway reversibility, hyperresponsiveness or airway variability.
Exclusion criteria:
- Smoking history: Current smokers or former smokers with a smoking history of >=10 pack years.
- Concurrent Respiratory Disease: Presence of a clinically important lung condition other than asthma.
- Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior screening
- Liver Disease: Unstable liver disease
- Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
- Other Concurrent Medical Conditions: Subjects 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: Subjects with other conditions that could lead to elevated eosinophils such as Hypereosiniophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic Esophaghitis. Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded.
- ECG: ECG assessment QTcF >=450 milliseconds (msec) or QTcF >= 480 msec for subjects with Bundle Branch Block.
- Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
- Omalizumab Use: Subjects who have received omalizumab [Xolair] within 130 days of Visit 1.
- Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
- Investigational Medications: 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, prior to Visit 1 (this also includes investigational formulations of marketed products).
- Hypersensitivity: Subjects with a known allergy or intolerance to a monoclonal antibody or biologic.
- Pregnancy: Subjects who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation.
- Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
- Adherence: Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.
- Previous participation: Subjects who have previously any study of mepolizumab and received Investigational Product.
Trial location(s)
Location
GSK Investigational Site
Rochester, Minnesota, United States, 55905
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bedford Park, South Australia, Australia, 5042
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45229
Status
Study Complete
Location
GSK Investigational Site
Montreal, Québec, Canada, H2X 2P4
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30173
Status
Study Complete
Location
GSK Investigational Site
Potsdam, Brandenburg, Germany, 14478
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
Status
Study Complete
Location
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
Status
Study Complete
Location
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Status
Study Complete
Location
GSK Investigational Site
New Haven, Connecticut, United States, 06520
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
New Lambton, New South Wales, Australia, 2305
Status
Study Complete
Location
GSK Investigational Site
Pittsburg, Pennsylvania, United States, PA 15213
Status
Study Complete
Location
GSK Investigational Site
Long Beach, California, United States, 90808
Status
Study Complete
Location
GSK Investigational Site
Leicester, Leicestershire, United Kingdom, LE3 9QP
Status
Study Complete
Location
GSK Investigational Site
Newcastle upon Tyne, United Kingdom, NE1 4LP
Status
Study Complete
Location
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23552
Status
Study Complete
Location
GSK Investigational Site
Ruedersdorf, Brandenburg, Germany, 15562
Status
Study Complete
Location
GSK Investigational Site
Denver, Colorado, United States, 80206
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
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
2013-12-12
Actual study completion date
2013-12-12
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.
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