Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma

March 21, 2017 updated by: GlaxoSmithKline

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
135

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • New Lambton, New South Wales, Australia, 2305
        • GSK Investigational Site
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • GSK Investigational Site
    • Victoria
      • Parkville, Victoria, Australia, 3050
        • GSK Investigational Site
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • GSK Investigational Site
  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N 4A6
        • GSK Investigational Site
    • Quebec
      • Montreal, Quebec, Canada, H4J 1C5
        • GSK Investigational Site
      • Montreal, Quebec, Canada, H2X 2P4
        • GSK Investigational Site
      • Quebec City, Quebec, Canada, G1V 4G5
        • GSK Investigational Site
  • Czech Republic
      • 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
        • GSK Investigational Site
  • France
      • 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
        • GSK Investigational Site
  • Germany
    • Bayern
      • Aschaffenburg, Bayern, Germany, 63739
        • GSK Investigational Site
    • Brandenburg
      • Potsdam, Brandenburg, Germany, 14478
        • GSK Investigational Site
      • Ruedersdorf, Brandenburg, Germany, 15562
        • GSK Investigational Site
    • Hessen
      • Frankfurt, Hessen, Germany, 60596
        • GSK Investigational Site
      • Gelnhausen, Hessen, Germany, 63571
        • GSK Investigational Site
      • Neu isenburg, Hessen, Germany, 63263
        • GSK Investigational Site
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30173
        • GSK Investigational Site
    • Rheinland-Pfalz
      • Mainz, Rheinland-Pfalz, Germany, 55131
        • GSK Investigational Site
    • Schleswig-Holstein
      • Luebeck, Schleswig-Holstein, Germany, 23552
        • GSK Investigational Site
  • Mexico
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44100
        • GSK Investigational Site
      • Zapopan, Jalisco, Mexico, 45040
        • GSK Investigational Site
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • GSK Investigational Site
      • Leeuwarden, Netherlands, 8934 AD
        • GSK Investigational Site
      • Rotterdam, Netherlands, 3045 PM
        • GSK Investigational Site
  • Poland
      • Bialystok, Poland, 15-044
        • GSK Investigational Site
      • Bialystok, Poland, 15-010
        • GSK Investigational Site
      • Krakow, Poland, 31-024
        • GSK Investigational Site
      • Lodz, Poland, 90-153
        • GSK Investigational Site
  • United Kingdom
      • Liverpool, United Kingdom, L9 7AL
        • GSK Investigational Site
      • Newcastle upon Tyne, United Kingdom, NE1 4LP
        • GSK Investigational Site
      • Southampton, United Kingdom, SO16 6YD
        • GSK Investigational Site
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE3 9QP
        • GSK Investigational Site
  • United States
    • California
      • Long Beach, California, United States, 90808
        • GSK Investigational Site
    • Colorado
      • Denver, Colorado, United States, 80206
        • GSK Investigational Site
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • GSK Investigational Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • GSK Investigational Site
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • GSK Investigational Site
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • GSK Investigational Site
    • Pennsylvania
      • Pittsburg, Pennsylvania, United States, PA 15213
        • GSK Investigational Site
    • South Carolina
      • Spartanburg, South Carolina, United States, 29303
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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: OCS (prednisone/prednisolone)
Oral Corticosteroid (prednisone/prednisolone)
Drug: Placebo
Will be available as an equivalent volume of 0.9% sodium chloride.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline; Weeks 20 to 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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
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.
Weeks 20 to 24
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.
Weeks 20 to 24
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.
Baseline; Weeks 20 to 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 20, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 24, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 23, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 21, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 115575

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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.

Study Data/Documents

  1. Study Protocol
    Information identifier: 115575
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  2. Dataset Specification
    Information identifier: 115575
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  3. Statistical Analysis Plan
    Information identifier: 115575
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  4. Annotated Case Report Form
    Information identifier: 115575
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  5. Clinical Study Report
    Information identifier: 115575
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  6. Informed Consent Form
    Information identifier: 115575
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  7. Individual Participant Data Set
    Information identifier: 115575
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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