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

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.

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

Conditions

Asthma

Study Type

Interventional

Study Design

Randomized, Parallel Assignment, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Treatment, Safety/Efficacy Study

Further Details

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 ]

 

Arms	Assigned Interventions
Placebo: Placebo Comparator Placebo saline every 4 weeks i.v.	Biological: Mepolizumab (treatment) – Severe asthma Mepolizumab 750mg, 250mg or75mg every four weeks i.v.
Mepolizumab 250mg: Active Comparator Mepolizumab 250mcg i.v. every 4 weeks	Biological: Mepolizumab (treatment) – Severe asthma Mepolizumab 750mg, 250mg or75mg every four weeks i.v.
Mepolizumab 750mg: Active Comparator Mepolizumab 750mcg i.v. every 4 weeks	Biological: Mepolizumab (treatment) – Severe asthma Mepolizumab 750mg, 250mg or 75mg every four weeks i.v.
Mepolizumab 75mg: Active Comparator Mepolizumab 75mcg	Biological: Mepolizumab (treatment) – Severe asthma Mepolizumab 750mg, 250mg or75mg 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.

Study Start

November 2009 – December 2011

Eligibility & Criteria

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

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 funtion 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 withing 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

Total Enrolment

604

Contact Details

US GSK Clinical Trials Call Center     877-379-3718

 

Australia, New South Wales
GSK Investigational Site	Recruiting
New Lambton, New South Wales, Australia, 2305
Principal Investigator: Peter G Gibson
Australia, South Australia
GSK Investigational Site
Adelaide, South Australia, Australia, 5000
Principal Investigator: Hubertus Jersmann
Australia, Victoria
GSK Investigational Site
Clayton, Victoria, Australia, 3168
Principal Investigator: Philip Bardin
GSK Investigational Site
Melbourne, Victoria, Australia, 3004
Principal Investigator: Jo Anne Douglass
Australia, Western Australia
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Principal Investigator: Philip Thompson