AzTrials
AzTrials

AsthmaPhase 3NCT01691508

Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma

A Phase 3 study testing Mepolizumab and OCS (prednisone/prednisolone) in people with Asthma, run by GlaxoSmithKline at 47 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Asthma
What is being tested?
Mepolizumab and OCS (prednisone/prednisolone)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
135 participants
Where
47 sitesin 10 countries
Study dates
Oct 2012to Dec 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 17Show fewer
  • 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 locations and contacts

47 sites in 10 countries.

47 sites in 10 countries

Germany9 sites

  • GSK Investigational Site

    Aschaffenburg, Bavaria, 63739

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60596

  • GSK Investigational Site

    Gelnhausen, Hesse, 63571

  • GSK Investigational Site

    Hanover, Lower Saxony, 30173

  • GSK Investigational Site

    Lübeck, Schleswig-Holstein, 23552

  • GSK Investigational Site

    Mainz, Rhineland-Palatinate, 55131

  • GSK Investigational Site

    Neu-Isenburg, Hesse, 63263

  • GSK Investigational Site

    Potsdam, Brandenburg, 14478

  • GSK Investigational Site

    Rüdersdorf, Brandenburg, 15562

Other trials in Germany

United States8 sites

  • GSK Investigational Site

    Cincinnati, Ohio, 45229

  • GSK Investigational Site

    Denver, Colorado, 80206

  • GSK Investigational Site

    Long Beach, California, 90808

  • GSK Investigational Site

    New Haven, Connecticut, 06520

  • GSK Investigational Site

    Pittsburgh, Pennsylvania, PA 15213

  • GSK Investigational Site

    Rochester, Minnesota, 55905

  • GSK Investigational Site

    Spartanburg, South Carolina, 29303

  • GSK Investigational Site

    St Louis, Missouri, 63110

Other trials in United States

France5 sites

  • GSK Investigational Site

    Gières, 38610

  • GSK Investigational Site

    Montpellier, 34295

  • GSK Investigational Site

    Nantes, 44093

  • GSK Investigational Site

    Paris, 75877

  • GSK Investigational Site

    Strasbourg, 67091

Other trials in France

Australia4 sites

  • GSK Investigational Site

    Bedford Park, South Australia, 5042

  • GSK Investigational Site

    Nedlands, Western Australia, 6009

  • GSK Investigational Site

    New Lambton, New South Wales, 2305

  • GSK Investigational Site

    Parkville, Victoria, 3050

Other trials in Australia

Canada4 sites

  • GSK Investigational Site

    Hamilton, Ontario, L8N 4A6

  • GSK Investigational Site

    Montreal, Quebec, H2X 2P4

  • GSK Investigational Site

    Montreal, Quebec, H4J 1C5

  • GSK Investigational Site

    Québec, Quebec, G1V 4G5

Other trials in Canada

Czechia4 sites

  • GSK Investigational Site

    Brno, 625 00

  • GSK Investigational Site

    Olomouc, 775 20

  • GSK Investigational Site

    Prague, 140 59

  • GSK Investigational Site

    Prague, 180 01

Other trials in Czechia

Poland4 sites

  • GSK Investigational Site

    Bialystok, 15-010

  • GSK Investigational Site

    Bialystok, 15-044

  • GSK Investigational Site

    Krakow, 31-024

  • GSK Investigational Site

    Lodz, 90-153

Other trials in Poland

United Kingdom4 sites

  • GSK Investigational Site

    Leicester, Leicestershire, LE3 9QP

  • GSK Investigational Site

    Liverpool, L9 7AL

  • GSK Investigational Site

    Newcastle upon Tyne, NE1 4LP

  • GSK Investigational Site

    Southampton, SO16 6YD

Other trials in United Kingdom

Netherlands3 sites

  • GSK Investigational Site

    Amsterdam, 1105 AZ

  • GSK Investigational Site

    Leeuwarden, 8934 AD

  • GSK Investigational Site

    Rotterdam, 3045 PM

Other trials in Netherlands

Mexico2 sites

  • GSK Investigational Site

    Guadalajara, Jalisco, 44100

  • GSK Investigational Site

    Zapopan, Jalisco, 45040

Other trials in Mexico

About this study

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

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.

Conditions
Asthma
Being tested
Mepolizumab, Placebo, OCS (prednisone/prednisolone)
Keywords
Safety, Steroid Reduction, Efficacy, SB-240563, Eosinophils, Quality of Life, Mepolizumab, Severe Refractory Asthma
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MepolizumabDrug

    Mepolizumab is a fully humanised Immunoglobulin G antibody (IgG1, kappa) with human heavy and light chain frameworks.

  • PlaceboDrug

    Will be available as an equivalent volume of 0.9% sodium chloride.

  • OCS (prednisone/prednisolone)Drug

    Oral Corticosteroid (prednisone/prednisolone)

Study groups in NCT01691508
Study groupRoleWhat they receive
MepolizumabExperimentalMepolizumab 100 mg subcutaneous once every 4 weeks upto Week 20
Receives: Drug: Mepolizumab; Drug: OCS (prednisone/prednisolone)
PlaceboExperimentalPlacebo subcutaneous once every 4 weeks upto Week 20
Receives: Drug: Placebo; Drug: OCS (prednisone/prednisolone)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    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.

    Measured: Baseline; Weeks 20 to 24

Secondary outcomes (4)

  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

    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.

    Measured: Baseline; Weeks 20 to 24

  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

    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.

    Measured: Weeks 20 to 24

  3. Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control

    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.

    Measured: Weeks 20 to 24

  4. Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control

    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.

    Measured: Baseline; Weeks 20 to 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Sep 2012 (estimated)
  2. Study startOct 2012
  3. Primary completionDec 2013
  4. Study completionDec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
135 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01691508
Sponsor's protocol ID
115575
Status last verified
Mar 2017
First submitted
20 Sep 2012
Last updated
23 Mar 2017
Data monitoring committee
Yes
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • Casale TB, Burnette A, Bourdin A, Howarth P, Hahn B, Stach-Klysh A, Khurana S. Oral corticosteroid-sparing effects of mepolizumab in severe eosinophilic asthma: evidence from randomized controlled trials and real-world studies. Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221107313. doi: 10.1177/17534666221107313.

    PubMed 35972211

  • Khurana S, Brusselle GG, Bel EH, FitzGerald JM, Masoli M, Korn S, Kato M, Albers FC, Bradford ES, Gilson MJ, Price RG, Humbert M. Long-term Safety and Clinical Benefit of Mepolizumab in Patients With the Most Severe Eosinophilic Asthma: The COSMEX Study. Clin Ther. 2019 Oct;41(10):2041-2056.e5. doi: 10.1016/j.clinthera.2019.07.007. Epub 2019 Aug 22.

    PubMed 31447130

  • Yancey SW, Bradford ES, Keene ON. Disease burden and efficacy of mepolizumab in patients with severe asthma and blood eosinophil counts of >/=150-300 cells/muL. Respir Med. 2019 May;151:139-141. doi: 10.1016/j.rmed.2019.04.008. Epub 2019 Apr 8.

    PubMed 31047111

  • Ortega HG, Meyer E, Brusselle G, Asano K, Prazma CM, Albers FC, Mallett SA, Yancey SW, Gleich GJ. Update on immunogenicity in severe asthma: Experience with mepolizumab. J Allergy Clin Immunol Pract. 2019 Sep-Oct;7(7):2469-2475.e1. doi: 10.1016/j.jaip.2019.03.042. Epub 2019 Apr 5. No abstract available.

    PubMed 30954640

  • Keene ON. Strategies for composite estimands in confirmatory clinical trials: Examples from trials in nasal polyps and steroid reduction. Pharm Stat. 2019 Jan;18(1):78-84. doi: 10.1002/pst.1909. Epub 2018 Oct 29.

    PubMed 30370691

  • Magnan A, Bourdin A, Prazma CM, Albers FC, Price RG, Yancey SW, Ortega H. Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment. Allergy. 2016 Sep;71(9):1335-44. doi: 10.1111/all.12914. Epub 2016 May 24.

    PubMed 27087007

  • Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1189-97. doi: 10.1056/NEJMoa1403291. Epub 2014 Sep 8.

    PubMed 25199060

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Mepolizumab and OCS (prednisone/prednisolone) in people with Asthma, run by GlaxoSmithKline at 47 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in Germany, United States, France, Australia, Canada and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01691508, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in