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: July 10, 2014
Last verified: June 2014
  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 750
Biological: Mepolizumab 250
Biological: Mepolizumab 75
Drug: Placebo saline
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: 604
Study Start Date: November 2009
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Mepolizumab 750mg
Mepolizumab 750mcg i.v. every 4 weeks
Biological: Mepolizumab 750
Mepolizumab 750mg every four weeks by i.v.
Active Comparator: Mepolizumab 250mg
Mepolizumab 250mcg i.v. every 4 weeks
Biological: Mepolizumab 250
Mepolizumab 250mg every four weeks by i.v.
Active Comparator: Mepolizumab 75mg
Mepolizumab 75mcg i.v. every 4 weeks
Biological: Mepolizumab 75
Mepolizumab 75mg every four weeks by i.v.
Placebo Comparator: Placebo
Placebo saline every 4 weeks i.v.
Drug: Placebo saline
Placebo saline every four weeks by 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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01000506

  Show 94 Study Locations
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: July 10, 2014
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 August 21, 2014