Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma
DREAM
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Dose Ranging Study to Determine the Effect of Mepolizumab on Exacerbation Rates in Subjects With Severe Uncontrolled Refractory Asthma
1 other identifier
interventional
621
13 countries
94
Brief Summary
The purpose of this study is to show whether mepolizumab given every 4 weeks intravenously (i.v.) can reduce the frequency of asthma exacerbations in subjects with severe asthma despite receiving high doses of standard asthma medications. The study will look at different doses of mepolizumab in comparison to a placebo.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 asthma
Started Nov 2009
Typical duration for phase_2 asthma
94 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 22, 2009
CompletedFirst Posted
Study publicly available on registry
October 23, 2009
CompletedStudy Start
First participant enrolled
November 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 23, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
March 23, 2012
CompletedResults Posted
Study results publicly available
February 5, 2016
CompletedJanuary 24, 2018
January 1, 2018
2.4 years
October 22, 2009
November 9, 2015
January 18, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Clinically Significant Exacerbations of Asthma Per Year
Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for participants on maintenance oral corticosteroids \[OCS\], an exacerbation requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or emergency department (ED) visit. The frequency of clinically significant exacerbations of asthma over the 52-week treatment period is expressed as exacerbation rate per year. Analysis of the number of exacerbations was performed using a negative binomial regression model with covariates of treatment group, Baseline (BL) maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and BL percent (%) predicted forced expiratory volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable
From randomization (Week 0) to Week 52 or early withdrawal (EW)
Secondary Outcomes (8)
Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit
From randomization (Week 0) to Week 52 or EW
Number of Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visit Per Year
From randomization (Week 0) to Week 52 or EW
Time to First Exacerbation Requiring Hospitalization or ED Visit
From randomization (Week 0) to Week 52 or EW
Number of All Recorded Exacerbations Per Year
From randomization (Week 0) to Week 52 or EW
Time to First All Recorded Exacerbation
From randomization (Week 0) to Week 52 or EW
- +3 more secondary outcomes
Study Arms (4)
Mepolizumab 750mg
ACTIVE COMPARATORMepolizumab 750mcg i.v. every 4 weeks
Mepolizumab 250mg
ACTIVE COMPARATORMepolizumab 250mcg i.v. every 4 weeks
Mepolizumab 75mg
ACTIVE COMPARATORMepolizumab 75mcg i.v. every 4 weeks
Placebo
PLACEBO COMPARATORPlacebo saline every 4 weeks i.v.
Interventions
Eligibility Criteria
You may qualify if:
- Male or female
- Aged 12 to 65 years inclusive
- Minimum weight 45kg
- Clinical features of severe refractory asthma
- Well documented requirement for high dose inhaled corticosteroids (ICS) \[i.e. \>= 880mcg/day fluticasone propionate or equivalent daily\] for at least 12 months
- Using additional controller medication in addition to high dose ICS for at least 12 months
- Persistent airflow obstruction indicated by a pre-bronchodilator FEV1\<80% predicted at visit 1 or 2 or peak flow diurnal variability of \>20% on 3 or more days during the run-in
- Airway inflammation which is likely to be eosinophilic in nature demonstrated by either raised peripheral blood eosinophils (\>=300/microL), sputum eosinophils (\>=3%), exhaled nitric oxide (\>=50ppb) or prompt deterioration of asthma control following a \<=25% reduction in regular maintenance dose of inhaled or oral corticosteroids (OCS)
- History of 2 or more exacerbations requiring systemic corticosteroids in the previous 12 months
- Evidence of asthma documented by airway reversibility, airway hyperresponsiveness or airflow variability
- ECG assessment demonstrating QTc\<450msec or QTc\<480msec for patients with bundle branch block
- Liver function tests demonstrating ALT\<2xUpper Limit of Normal (ULN), AST\<2xULN, Alk Phos \<=1.5xULN, bilirubin \<=1.5xULN
- Female of non-child-bearing potential or child-bearing potential with a negative pregnancy test at screening and prepared to agree to an acceptable method of contraception
- Able to give written informed consent
- Able to read, comprehend and write at a sufficient level to complete study materials
You may not qualify if:
- Current smokers or smoking history of \>=10 pack years
- Clinically important lung condition other than asthma
- Diagnosis of malignancy or in the process of investigation
- Unstable liver disease
- Churg-Strauss syndrome
- Using methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine or any experimental anti-inflammatory therapy within 3 months of screening
- Omalizumab (Xolair) or any other biological for the treatment of inflammatory disease within 6 months of Visit 1
- Regular use of oral or systemic corticosteroids for diseases other than asthma within 12 months or any intra-articular, short-acting intramuscular corticosteroid within 1 month or intramuscular, long-acting depot corticosteroid within 3 months
- Allergy/intolerance to the excipients in the mepolizumab formulation
- Any investigational drug within 30 days or 5 terminal half-lives, whichever is longer
- Pregnant or breastfeeding or planning to become pregnant
- Clinically significant disease which is uncontrolled with standard treatment
- History of alcohol misuse or substance abuse
- Parasitic infestation within previous 6 months
- Known immunodeficiency
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (94)
GSK Investigational Site
Long Beach, California, 90808, United States
GSK Investigational Site
Los Angeles, California, 90095, United States
GSK Investigational Site
Riverside, California, 92506, United States
GSK Investigational Site
San Diego, California, 92103-8415, United States
GSK Investigational Site
Denver, Colorado, 80206, United States
GSK Investigational Site
New Haven, Connecticut, 06510, United States
GSK Investigational Site
Albany, Georgia, 31707, United States
GSK Investigational Site
Columbus, Georgia, 31904, United States
GSK Investigational Site
Lexington, Kentucky, 40508, United States
GSK Investigational Site
St Louis, Missouri, 63110, United States
GSK Investigational Site
Winston-Salem, North Carolina, 27103, United States
GSK Investigational Site
Canton, Ohio, 44718, United States
GSK Investigational Site
Cleveland, Ohio, 44195, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73103, United States
GSK Investigational Site
Hershey, Pennsylvania, 17033, United States
GSK Investigational Site
Pittsburgh, Pennsylvania, PA 15213, United States
GSK Investigational Site
Charleston, South Carolina, 29406, United States
GSK Investigational Site
Nashville, Tennessee, 37203, United States
GSK Investigational Site
Boerne, Texas, 78006, United States
GSK Investigational Site
Houston, Texas, 77054, United States
GSK Investigational Site
Madison, Wisconsin, 53792, United States
GSK Investigational Site
Mar del Plata, Buenos Aires, B7600FZN, Argentina
GSK Investigational Site
Buenos Aires, 1425, Argentina
GSK Investigational Site
Buenos Aires, C1426ABP, Argentina
GSK Investigational Site
Mendoza, M5500CCG, Argentina
GSK Investigational Site
San Miguel de Tucumán, 4000, Argentina
GSK Investigational Site
New Lambton, New South Wales, 2305, Australia
GSK Investigational Site
Adelaide, South Australia, 5000, Australia
GSK Investigational Site
Clayton, Victoria, 3168, Australia
GSK Investigational Site
Melbourne, Victoria, 3004, Australia
GSK Investigational Site
Nedlands, Western Australia, 6009, Australia
GSK Investigational Site
Calgary, Alberta, T2N 4Z6, Canada
GSK Investigational Site
Vancouver, British Columbia, V5Z 1M9, Canada
GSK Investigational Site
Mississauga, Ontario, L5A 3V4, Canada
GSK Investigational Site
Mississauga, Ontario, L5M 2V8, Canada
GSK Investigational Site
Québec, Quebec, G1V 4G5, Canada
GSK Investigational Site
Valparaíso, Región de Valparaíso, 2341131, Chile
GSK Investigational Site
Puente Alto - Santiago, Región Metro de Santiago, 8207257, Chile
GSK Investigational Site
Santiago, 8380453, Chile
GSK Investigational Site
Talcahuano, 4270918, Chile
GSK Investigational Site
Clamart, 92140, France
GSK Investigational Site
Marseille, 13915, France
GSK Investigational Site
Montpellier, 34295, France
GSK Investigational Site
Nantes, 44093, France
GSK Investigational Site
Saint-Pierre, 97448, France
GSK Investigational Site
Rüdersdorf, Brandenburg, 15562, Germany
GSK Investigational Site
Frankfurt am Main, Hesse, 60596, Germany
GSK Investigational Site
Mainz, Rhineland-Palatinate, 55131, Germany
GSK Investigational Site
Magdeburg, Saxony-Anhalt, 39112, Germany
GSK Investigational Site
Lübeck, Schleswig-Holstein, 23552, Germany
GSK Investigational Site
Berlin, 10367, Germany
GSK Investigational Site
Berlin, 10717, Germany
GSK Investigational Site
Berlin, 12203, Germany
GSK Investigational Site
Berlin, 14050, Germany
GSK Investigational Site
Bialystok, 15-276, Poland
GSK Investigational Site
Lodz, 90-153, Poland
GSK Investigational Site
Warsaw, 01-138, Poland
GSK Investigational Site
Wroclaw, 54-239, Poland
GSK Investigational Site
Zawadzkie, 47-120, Poland
GSK Investigational Site
Zgierz, 95-100, Poland
GSK Investigational Site
Bucharest, 050159, Romania
GSK Investigational Site
Bucharest, 70000, Romania
GSK Investigational Site
Iași, 700115, Romania
GSK Investigational Site
Târgu Mureş, 540143, Romania
GSK Investigational Site
Barnaul, 656 045, Russia
GSK Investigational Site
Chelyabinsk, 454106, Russia
GSK Investigational Site
Kazan', 420015, Russia
GSK Investigational Site
Moscow, 105 077, Russia
GSK Investigational Site
Moscow, 115478, Russia
GSK Investigational Site
Moscow, 123 182, Russia
GSK Investigational Site
Saint Petersburg, 194354, Russia
GSK Investigational Site
Saint Petersburg, 198216, Russia
GSK Investigational Site
Tomsk, 634001, Russia
GSK Investigational Site
Bucheon-si, 420-767, South Korea
GSK Investigational Site
Cheongju, Chungcheongbuk-do, 361-711, South Korea
GSK Investigational Site
Seoul, 133--792, South Korea
GSK Investigational Site
Seoul, 152-703, South Korea
GSK Investigational Site
Suwon, Kyonggi-do, 443-721, South Korea
GSK Investigational Site
Cherkassy, 18009, Ukraine
GSK Investigational Site
Dnipropetrovsk, 49006, Ukraine
GSK Investigational Site
Dnipropetrovsk, 49027, Ukraine
GSK Investigational Site
Dnipropetrovsk, 49051, Ukraine
GSK Investigational Site
Donetsk, 83003, Ukraine
GSK Investigational Site
Donetsk, 83099, Ukraine
GSK Investigational Site
Kharkiv, 61035, Ukraine
GSK Investigational Site
Kiev, 03680, Ukraine
GSK Investigational Site
Kyiv, 03038, Ukraine
GSK Investigational Site
Kyiv, 03115, Ukraine
GSK Investigational Site
Mykolayiv, 54003, Ukraine
GSK Investigational Site
Leicester, Leicestershire, LE3 9QP, United Kingdom
GSK Investigational Site
London, E1 2AT, United Kingdom
GSK Investigational Site
London, SW3 6HP, United Kingdom
GSK Investigational Site
Manchester, M23 9LT, United Kingdom
GSK Investigational Site
Southampton, SO16 6YD, United Kingdom
Related Publications (9)
Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):651-9. doi: 10.1016/S0140-6736(12)60988-X.
PMID: 22901886BACKGROUNDChen W, Reddel HK, FitzGerald JM, Beasley R, Janson C, Sadatsafavi M. Can we predict who will benefit most from biologics in severe asthma? A post-hoc analysis of two phase 3 trials. Respir Res. 2023 May 2;24(1):120. doi: 10.1186/s12931-023-02409-2.
PMID: 37131185DERIVEDGibson PG, Prazma CM, Chupp GL, Bradford ES, Forshag M, Mallett SA, Yancey SW, Smith SG, Bel EH. Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions. Respir Res. 2021 Jun 7;22(1):171. doi: 10.1186/s12931-021-01746-4.
PMID: 34098955DERIVEDKim MK, Park HS, Park CS, Min SJ, Albers FC, Yancey SW, Mayer B, Kwon N. Efficacy and safety of mepolizumab in Korean patients with severe eosinophilic asthma from the DREAM and MENSA studies. Korean J Intern Med. 2021 Mar;36(2):362-370. doi: 10.3904/kjim.2019.198. Epub 2020 May 26.
PMID: 32450626DERIVEDOrtega 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.
PMID: 30954640DERIVEDOrtega H, Yancey SW, Keene ON, Gunsoy NB, Albers FC, Howarth PH. Asthma Exacerbations Associated with Lung Function Decline in Patients with Severe Eosinophilic Asthma. J Allergy Clin Immunol Pract. 2018 May-Jun;6(3):980-986.e1. doi: 10.1016/j.jaip.2017.12.019. Epub 2018 Feb 15.
PMID: 29398640DERIVEDGunsoy NB, Cockle SM, Yancey SW, Keene ON, Bradford ES, Albers FC, Pavord ID. Evaluation of Potential Continuation Rules for Mepolizumab Treatment of Severe Eosinophilic Asthma. J Allergy Clin Immunol Pract. 2018 May-Jun;6(3):874-882.e4. doi: 10.1016/j.jaip.2017.11.026. Epub 2017 Dec 16.
PMID: 29258789DERIVEDOrtega H, Li H, Suruki R, Albers F, Gordon D, Yancey S. Cluster analysis and characterization of response to mepolizumab. A step closer to personalized medicine for patients with severe asthma. Ann Am Thorac Soc. 2014 Sep;11(7):1011-7. doi: 10.1513/AnnalsATS.201312-454OC.
PMID: 24983709DERIVEDPrazma CM, Wenzel S, Barnes N, Douglass JA, Hartley BF, Ortega H. Characterisation of an OCS-dependent severe asthma population treated with mepolizumab. Thorax. 2014 Dec;69(12):1141-2. doi: 10.1136/thoraxjnl-2014-205581. Epub 2014 May 16.
PMID: 24834924DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 22, 2009
First Posted
October 23, 2009
Study Start
November 1, 2009
Primary Completion
March 23, 2012
Study Completion
March 23, 2012
Last Updated
January 24, 2018
Results First Posted
February 5, 2016
Record last verified: 2018-01
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.