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Phase 2 N=616 Randomized Quadruple-blind Treatment

Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma

Asthma

Enrolled (actual)
616
Serious AEs
14.3%
Results posted
Feb 2016
Primary outcome: Primary: Number of Clinically Significant Exacerbations of Asthma Per Year — 2.40; 1.24; 1.46; 1.15 Exacerbations per year — p=<0.001

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Mepolizumab 750 (Biological); Mepolizumab 250 (Biological); Mepolizumab 75 (Biological); Placebo saline (Drug)
Age
Pediatric, Adult, Older Adult · 12+ yrs
Sex
All
Sponsor
GlaxoSmithKline
Primary completion
Mar 2012

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Clinically Significant Exacerbations of Asthma Per Year
2.40; 1.24; 1.46; 1.15 <0.001 sig
SECONDARY
Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit
45.2; 22.8; 26.8; 18.9; 60.4; 38.2
SECONDARY
Number of Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visit Per Year
0.43; 0.17; 0.25; 0.22
SECONDARY
Time to First Exacerbation Requiring Hospitalization or ED Visit
8.6; 3.4; 6.7; 3.9; 14.8; 8.3
SECONDARY
Number of All Recorded Exacerbations Per Year
2.46; 1.34; 1.49; 1.20
SECONDARY
Time to First All Recorded Exacerbation
45.9; 26.1; 27.5; 19.6; 60.9; 41.5
SECONDARY
Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period
149; 163; 137; 112; 154; 165
SECONDARY
Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period
59; 77; 50; 87; 40; 49
SECONDARY
Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period
-0.45; -0.61; -0.50; -0.56; -0.50; -0.73

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.

Eligibility 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 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 =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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01000506). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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