Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma (DREAM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01000506
First received: October 22, 2009
Last updated: September 19, 2013
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Asthma
Biological: Mepolizumab (treatment) - Severe asthma
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Frequency of clinically significant exacerbations of asthma [ Time Frame: 52-weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to first clinically significant exacerbation requiring oral or systemic corticosteroids, hospitalisation, and/or ED visits [ Time Frame: 52-weeks ] [ Designated as safety issue: No ]
  • Frequency of exacerbations requiring hospitalization (including intubation and admittance to an ICU) or ED visits [ Time Frame: 52-weeks ] [ Designated as safety issue: No ]
  • Time to first exacerbation requiring hospitalization or ED visit [ Time Frame: 52-weeks ] [ Designated as safety issue: No ]
  • Frequency of investigator-defined exacerbations [ Time Frame: 52-weeks ] [ Designated as safety issue: No ]
  • Time to first investigator-defined exacerbation [ Time Frame: 52-weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline in clinic pre-bronchodilator FEV1 over the 52-week treatment period [ Time Frame: 52-weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline in clinic post-bronchodilator FEV1 over the 52 week treatment period [ Time Frame: 52-weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline in Asthma Control Questionnaire (ACQ) score [ Time Frame: 52-weeks ] [ Designated as safety issue: No ]

Enrollment: 621
Study Start Date: November 2009
Study Completion Date: March 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Mepolizumab 750mg
Mepolizumab 750mcg i.v. every 4 weeks
Biological: Mepolizumab (treatment) - Severe asthma
Mepolizumab 750mg, 250mg or 75mg every four weeks i.v.
Active Comparator: Mepolizumab 250mg
Mepolizumab 250mcg i.v. every 4 weeks
Biological: Mepolizumab (treatment) - Severe asthma
Mepolizumab 750mg, 250mg or 75mg every four weeks i.v.
Active Comparator: Mepolizumab 75mg
Mepolizumab 75mcg i.v. every 4 weeks
Biological: Mepolizumab (treatment) - Severe asthma
Mepolizumab 750mg, 250mg or 75mg every four weeks i.v.
Placebo Comparator: Placebo
Placebo saline every 4 weeks i.v.
Biological: Mepolizumab (treatment) - Severe asthma
Mepolizumab 750mg, 250mg or 75mg every four weeks i.v.

Detailed Description:

A double-blind, placebo-controlled study to evaluate the efficacy, safety and pharmacodynamics of three doses (75 mg, 250 mg and 750 mg) of mepolizumab intravenous (i.v.) administered every 4 weeks compared with placebo over a 52-week treatment period in subjects with severe uncontrolled refractory asthma. Efficacy will be measured by the frequency of asthma exacerbations. In addition lung function, rescue medication usage, daily symptoms, asthma control score, asthma quality of life score and withdrawals due to asthma exacerbations will be assessed. Safety will be assessed by adverse events, clinical laboratory evaluations, ECGs, immunogenicity and vital signs. Pharmacodynamics will be assessed by eosinophil levels in blood, serum IL-5 and eosinophil levels in induced sputum.

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Unable to follow instructions, use the electronic diary or peak flow meter
  • Known evidence of lack of adherence to controller medications and/or follow physician's recommendations
  • Previous participation in a study of mepolizumab and received study medication within 90 days
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01000506

  Hide Study Locations
Locations
United States, California
GSK Investigational Site
Long Beach, California, United States, 90808
GSK Investigational Site
Los Angeles, California, United States, 90095
GSK Investigational Site
Riverside, California, United States, 92506
GSK Investigational Site
San Diego, California, United States, 92103-8415
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80206
United States, Connecticut
GSK Investigational Site
New Haven, Connecticut, United States, 06510
United States, Georgia
GSK Investigational Site
Albany, Georgia, United States, 31707
GSK Investigational Site
Columbus, Georgia, United States, 31904
United States, Kentucky
GSK Investigational Site
Lexington, Kentucky, United States, 40508
United States, Missouri
GSK Investigational Site
St. Louis, Missouri, United States, 63110
United States, North Carolina
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
GSK Investigational Site
Canton, Ohio, United States, 44718
GSK Investigational Site
Cleveland, Ohio, United States, 44195
United States, Oklahoma
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73103
United States, Pennsylvania
GSK Investigational Site
Hershey, Pennsylvania, United States, 17033
GSK Investigational Site
Pittsburg, Pennsylvania, United States, PA 15213
United States, South Carolina
GSK Investigational Site
Charleston, South Carolina, United States, 29406
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Boerne, Texas, United States, 78006
GSK Investigational Site
Houston, Texas, United States, 77054
United States, Wisconsin
GSK Investigational Site
Madison, Wisconsin, United States, 53792
Argentina
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, B7600FZN
GSK Investigational Site
Buenos Aires, Argentina, 1425
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1426ABO
GSK Investigational Site
Mendoza, Argentina, M5500CCG
GSK Investigational Site
Tucuman, Argentina, 4000
Australia, New South Wales
GSK Investigational Site
New Lambton, New South Wales, Australia, 2305
Australia, South Australia
GSK Investigational Site
Adelaide, South Australia, Australia, 5000
Australia, Victoria
GSK Investigational Site
Clayton, Victoria, Australia, 3168
GSK Investigational Site
Melbourne, Victoria, Australia, 3004
Australia, Western Australia
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Canada, Alberta
GSK Investigational Site
Calgary, Alberta, Canada, T2N 4Z6
Canada, British Columbia
GSK Investigational Site
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
GSK Investigational Site
Mississauga, Ontario, Canada, L5M 2V8
GSK Investigational Site
Mississauga, Ontario, Canada, L5A 3V4
Canada, Quebec
GSK Investigational Site
Quebec City, Quebec, Canada, G1V 4G5
Chile
GSK Investigational Site
Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
GSK Investigational Site
Valparaiso, Valparaíso, Chile, 2341131
GSK Investigational Site
Santiago, Chile, 8380453
GSK Investigational Site
Talcahuano, Chile, 4270918
France
GSK Investigational Site
Clamart, France, 92140
GSK Investigational Site
Marseille cedex 20, France, 13915
GSK Investigational Site
Montpellier, France, 34295
GSK Investigational Site
Nantes, France, 44093
GSK Investigational Site
Saint Pierre cedex, France, 97448
Germany
GSK Investigational Site
Ruedersdorf, Brandenburg, Germany, 15562
GSK Investigational Site
Frankfurt, Hessen, Germany, 60596
GSK Investigational Site
Frankfurt am Main, Hessen, Germany, 60596
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39112
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23552
GSK Investigational Site
Berlin, Germany, 14050
GSK Investigational Site
Berlin, Germany, 10367
GSK Investigational Site
Berlin, Germany, 10717
GSK Investigational Site
Berlin, Germany, 12203
Korea, Republic of
GSK Investigational Site
Bucheon-si,, Korea, Republic of, 420-767
GSK Investigational Site
Cheongju, Chungcheongbuk-do, Korea, Republic of, 361-711
GSK Investigational Site
Seoul, Korea, Republic of, 152-703
GSK Investigational Site
Seoul, Korea, Republic of, 133--792
GSK Investigational Site
Suwon, Kyonggi-do, Korea, Republic of, 443-721
Poland
GSK Investigational Site
Bialystok, Poland, 15-276
GSK Investigational Site
Lodz, Poland, 90-153
GSK Investigational Site
Warszawa, Poland, 01-138
GSK Investigational Site
Wroclaw, Poland, 54-239
GSK Investigational Site
Zawadzkie, Poland, 47-120
GSK Investigational Site
Zgierz, Poland, 95-100
Romania
GSK Investigational Site
Bucharest, Romania, 050159
GSK Investigational Site
Bucuresti, Romania, 70000
GSK Investigational Site
Iasi, Romania, 700115
GSK Investigational Site
Targu Mures, Romania, 540143
Russian Federation
GSK Investigational Site
Barnaul, Russian Federation, 656 045
GSK Investigational Site
Chelyabinsk, Russian Federation, 454106
GSK Investigational Site
Kazan, Russian Federation, 420015
GSK Investigational Site
Moscow, Russian Federation, 115478
GSK Investigational Site
Moscow, Russian Federation, 105 077
GSK Investigational Site
Moscow, Russian Federation, 123 182
GSK Investigational Site
Saint-Petersburg, Russian Federation, 194354
GSK Investigational Site
St. Petersburg, Russian Federation, 198216
GSK Investigational Site
Tomsk, Russian Federation, 634001
Ukraine
GSK Investigational Site
Cherkassy, Ukraine, 18009
GSK Investigational Site
Dnipropetrovsk, Ukraine, 49027
GSK Investigational Site
Dnipropetrovsk, Ukraine, 49051
GSK Investigational Site
Dnipropetrovsk, Ukraine, 49006
GSK Investigational Site
Donetsk, Ukraine, 83003
GSK Investigational Site
Donetsk, Ukraine, 83099
GSK Investigational Site
Kharkiv, Ukraine, 61035
GSK Investigational Site
Kiev, Ukraine, 03680
GSK Investigational Site
Kyiv, Ukraine, 03115
GSK Investigational Site
Mykolayiv, Ukraine, 54003
United Kingdom
GSK Investigational Site
Leicester, Leicestershire, United Kingdom, LE3 9QP
GSK Investigational Site
London, United Kingdom, Sw3 6HP
GSK Investigational Site
London, United Kingdom, E1 2AT
GSK Investigational Site
Manchester, United Kingdom, M23 9LT
GSK Investigational Site
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01000506     History of Changes
Other Study ID Numbers: 112997
Study First Received: October 22, 2009
Last Updated: September 19, 2013
Health Authority: Chile: Institutional Review Board
Romania: National Drug Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Argentina: Ministry of Health - A.N.M.A.T
Australia: Medicines Australia
Russia: Russian Ministry of Health
Ukraine: State Pharmacological Center of Ministry of Health of Ukraine
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
France: Agence Française de Sécurité Sanitaire des Produits de Santé
United States: Institutional Review Board
Poland: Ministry of Health & Social Welfare
South Korea: Food and Drug Administration
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Dose-ranging
Safety
Pharmacodynamics
eosinophils
SB-240563
Efficacy
Severe refractory asthma
mepolizumab
Placebo

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on April 14, 2014