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Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01691508
Recruitment Status : Completed
First Posted : September 24, 2012
Results First Posted : January 26, 2016
Last Update Posted : March 23, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Asthma Drug: Mepolizumab Drug: Placebo Drug: OCS (prednisone/prednisolone) Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 135 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Study Start Date : October 2012
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Steroids
Drug Information available for: Mepolizumab

Arm Intervention/treatment
Experimental: Mepolizumab
Mepolizumab 100 mg subcutaneous once every 4 weeks upto Week 20
Drug: Mepolizumab
Mepolizumab is a fully humanised Immunoglobulin G antibody (IgG1, kappa) with human heavy and light chain frameworks.

Drug: OCS (prednisone/prednisolone)
Oral Corticosteroid (prednisone/prednisolone)

Experimental: Placebo
Placebo subcutaneous once every 4 weeks upto Week 20
Drug: Placebo
Will be available as an equivalent volume of 0.9% sodium chloride.

Drug: OCS (prednisone/prednisolone)
Oral Corticosteroid (prednisone/prednisolone)




Primary Outcome Measures :
  1. Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control [ Time Frame: Baseline; Weeks 20 to 24 ]
    Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The percent reduction of OCS was categorized as: 90 to 100%; 75 to <90%; 50 to <75%; >0 to <50%; no decrease in prednisone dose, or lack of asthma control, or withdrawal (WD) from treatment. Analysis was performed using a proportional odds model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.


Secondary Outcome Measures :
  1. 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 [ Time Frame: Baseline; Weeks 20 to 24 ]
    Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.

  2. 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 [ Time Frame: Weeks 20 to 24 ]
    Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Number of participants who achieved a reduction of their daily OCS dose to <=5.0 mg was based on the value of the MN dose. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.

  3. Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control [ Time Frame: Weeks 20 to 24 ]
    MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The number of participants who achieved a total reduction of OCS dose was based on the value of the MN dose. Total reduction implied no OCS use during the entire MN phase. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.

  4. Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control [ Time Frame: Baseline; Weeks 20 to 24 ]
    BL dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent change of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (MN dose minus BL dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. For participants who withdrew from the study prior to the Maintenance Phase, and for participants with a lack of asthma control during the Maintenance Phase, a value equal to the minimum percent reduction in OCS use across all subjects was imputed for the analysis.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01691508


Locations
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United States, California
GSK Investigational Site
Long Beach, California, United States, 90808
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80206
United States, Connecticut
GSK Investigational Site
New Haven, Connecticut, United States, 06520
United States, Minnesota
GSK Investigational Site
Rochester, Minnesota, United States, 55905
United States, Missouri
GSK Investigational Site
St. Louis, Missouri, United States, 63110
United States, Ohio
GSK Investigational Site
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
GSK Investigational Site
Pittsburg, Pennsylvania, United States, PA 15213
United States, South Carolina
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
Australia, New South Wales
GSK Investigational Site
New Lambton, New South Wales, Australia, 2305
Australia, South Australia
GSK Investigational Site
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
GSK Investigational Site
Parkville, Victoria, Australia, 3050
Australia, Western Australia
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Canada, Ontario
GSK Investigational Site
Hamilton, Ontario, Canada, L8N 4A6
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H2X 2P4
GSK Investigational Site
Montreal, Quebec, Canada, H4J 1C5
GSK Investigational Site
Quebec City, Quebec, Canada, G1V 4G5
Czech Republic
GSK Investigational Site
Brno, Czech Republic, 625 00
GSK Investigational Site
Olomouc, Czech Republic, 775 20
GSK Investigational Site
Praha 4, Czech Republic, 140 59
GSK Investigational Site
Praha 8, Czech Republic, 180 01
France
GSK Investigational Site
Gières, France, 38610
GSK Investigational Site
Montpellier cedex 5, France, 34295
GSK Investigational Site
Nantes cedex 1, France, 44093
GSK Investigational Site
Paris Cedex 18, France, 75877
GSK Investigational Site
Strasbourg, France, 67091
Germany
GSK Investigational Site
Aschaffenburg, Bayern, Germany, 63739
GSK Investigational Site
Potsdam, Brandenburg, Germany, 14478
GSK Investigational Site
Ruedersdorf, Brandenburg, Germany, 15562
GSK Investigational Site
Frankfurt, Hessen, Germany, 60596
GSK Investigational Site
Gelnhausen, Hessen, Germany, 63571
GSK Investigational Site
Neu isenburg, Hessen, Germany, 63263
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30173
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23552
Mexico
GSK Investigational Site
Guadalajara, Jalisco, Mexico, 44100
GSK Investigational Site
Zapopan, Jalisco, Mexico, 45040
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1105 AZ
GSK Investigational Site
Leeuwarden, Netherlands, 8934 AD
GSK Investigational Site
Rotterdam, Netherlands, 3045 PM
Poland
GSK Investigational Site
Bialystok, Poland, 15-010
GSK Investigational Site
Bialystok, Poland, 15-044
GSK Investigational Site
Krakow, Poland, 31-024
GSK Investigational Site
Lodz, Poland, 90-153
United Kingdom
GSK Investigational Site
Leicester, Leicestershire, United Kingdom, LE3 9QP
GSK Investigational Site
Liverpool, United Kingdom, L9 7AL
GSK Investigational Site
Newcastle upon Tyne, United Kingdom, NE1 4LP
GSK Investigational Site
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
Additional Information:
Study Data/Documents: Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 115575
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 115575
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 115575
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 115575
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 115575
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 115575
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 115575
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01691508    
Other Study ID Numbers: 115575
First Posted: September 24, 2012    Key Record Dates
Results First Posted: January 26, 2016
Last Update Posted: March 23, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Keywords provided by GlaxoSmithKline:
Safety
Steroid Reduction
Efficacy
SB-240563
Eosinophils
Quality of Life
Mepolizumab
Severe Refractory Asthma
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Prednisone
Prednisolone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents