Clinical Trial: Effects of Mepolizumab Compared to Placebo on Airway Physiology in Patients With Eosinophilic Asthma: MEMORY Study

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Randomized, Double-blind, Placebo-controlled, Mono-center Study to Evaluate the Effects of Mepolizumab on Airway Physiology in Patients With Eosinophilic Asthma: the MEM

Brief Summary: The purpose of the MEMORY trial is to compare the effects of mepolizumab with Placebo on airway physiology in patients with eosinophilic asthma

Detailed Summary:

Asthma with eosinophilic inflammation in the airways and/or blood eosinophilia is associated with clinical severity including the risk of exacerbations and relevant comorbidities (e.g. nasal polyposis). Interleukin-5 (IL-5) is a cytokine essential for eosinophil trafficking and survival. Clinical trials of blocking IL-5 with anti-IL-5 antibodies (mepolizumab and reslizumab) in patients with uncontrolled eosinophilic asthma resulted in an improvement in exacerbation rate and oral corticosteroid use. In some studies with mepolizumab and reslizumab there was a beneficial effect on lung function (FEV1). In addition, many patients described a profound impact on asthma symptoms and quality of life in personal reports which is not uniformly reflected in clinical trials.

The MEMORY trial is the first to primarily evaluate the effect of mepolizumab treatment on pulmonary function in patients with severe eosinophilic asthma. Importantly, using spirometry and bodyplethysmography will allow to evaluate additional parameters beyond FEV1 that more closely mirror the pathophysiological changes and functional aspects of airflow limitation in asthma in real life, e.g. airway resistance, hyperinflation and diffusion capacity. The proposed trial will answer the important questions: if, and if so, which parameters of airway (patho-) physiology as assessed by bodyplethysmography best reflect clinical response to mepolizumab therapy in patients with severe eosinophilic asthma. In addition, the time course to clinical response will be assessed. Equally important, there is only a loose correlation between FEV1 and parameters of asthma control and asthma-related quality of life. This is why another new and important aspect of this trial is to carefully monitor asthma control and asthma quality in life in correlation with lung function changes beyond FEV1. Finally, it is tempting to speculate that
Sponsor: Johannes Gutenberg University Mainz

Current Primary Outcome:

  • mean change from baseline in pre- and post-bronchodilator FVC at visit 10 (week 24) and at time of response [ Time Frame: week 24 and time of response ]
    The primary outcome is the mean change from baseline in pre- and post-bronchodilator forced vital capacity (FVC) at visit 10 (week 24) and at time of response
  • mean change from baseline in pre- and post-bronchodilator FEV1 at visit 10 (week 24) and at time of response [ Time Frame: week 24 and time of response ]
    The primary outcome is the mean change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) at visit 10 (week 24) and at time of response
  • mean change from baseline in pre- and post-bronchodilator RV at visit 10 (week 24) and at time of response [ Time Frame: week 24 and time of response ]
    The primary outcome is the mean change from baseline in pre- and post-bronchodilator residual volume (RV) at visit 10 (week 24) and at time of response
  • mean change from baseline in pre- and post-bronchodilator TLC at visit 10 (week 24) and at time of response [ Time Frame: week 24 and time of response ]
    The primary outcome is the mean change from baseline in pre- and post-bronchodilator total lung capacity (TLC) at visit 10 (week 24) and at time of response
  • mean change from baseline in pre- and post-bronchodilator airway resistance at visit 10 (week 24) and at time of response [ Time Frame: week 24 and time of response ]
    The primary outcome is t

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Mean change from baseline in pre- and post-bronchodilator forced vital capacity (FVC) over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months) [ Time Frame: 1, 3, 6, 9 and 12 months ]
    • Mean change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months) [ Time Frame: 1, 3, 6, 9 and 12 months ]
    • Mean change from baseline in pre- and post-bronchodilator residual volume (RV) over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months) [ Time Frame: 1, 3, 6, 9 and 12 months ]
    • Mean change from baseline in pre- and post-bronchodilator total lung capacity (TLC) over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months) [ Time Frame: 1, 3, 6, 9 and 12 months ]
    • Mean change from baseline in pre- and post-bronchodilator airway resistance over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months) [ Time Frame: 1, 3, 6, 9 and 12 months ]
    • Mean change from baseline in pre- and post-bronchodilator inspiratory capacity (IC) over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months) [ Time Frame: 1, 3, 6, 9 and 12 months ]
    • Mean change from baseline in pre- and post-bronchodilator CO diffusion capacity over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months) [ Time Frame: 1, 3, 6, 9 and 12 months ]
    • Exercise tolerance in a subgroup of patients: Mean change from baseline in exercise endurance time [ Time Frame: 1, 3, 6, 9 and 12 month ]
      Mean change from baseline in exercise endurance time during a sub-maximal constant-load cycle ergometry test after 1, 3, 6, 9 and 12 months of treatment.
    • Exercise tolerance in a subgroup of patients: Mean change from baseline in inspiratory capacity (IC) [ Time Frame: 1, 3, 6, 9 and 12 month ]
      Mean change from baseline in inspiratory capacity (IC) at rest and at peak during sub-maximal constant-load cycle ergometry test after 1, 3, 6, 9 and 12 months of treatment.
    • Exercise tolerance in a subgroup of patients: Mean change from baseline in exertional dyspnea and leg discomfort (Borg CR10 Scale®) [ Time Frame: 1, 3, 6, 9 and 12 month ]
      Mean change from baseline in exertional dyspnea and leg discomfort (Borg CR10 Scale®) during sub-maximal constant-load cycle ergometry test after 1, 3, 6, 9 and 12 months of treatment
    • Time to clinical response and time to change of baseline parameters of clinical Response: sence of smell [ Time Frame: 52 weeks ]
    • Time to clinical response and time to change of baseline parameters of clinical Response: sense of taste [ Time Frame: 52 weeks ]
    • Time to clinical response and time to change of baseline parameters of clinical Response: lung volume [ Time Frame: 52 weeks ]
    • Time to clinical response and time to change of baseline parameters of clinical Response: CO Diffusion capacity [ Time Frame: 52 weeks ]
    • Time to clinical response and time to change of baseline parameters of clinical Response: FEV1 reversibility [ Time Frame: 52 weeks ]
    • Time to clinical response and time to change of baseline parameters of clinical Response: exhaled NO (eNO) [ Time Frame: 52 weeks ]
    • Time to clinical response and time to change of baseline parameters of clinical Response: blood eosinophils [ Time Frame: 52 weeks ]
    • Time to clinical response and time to change of baseline parameters of clinical Response: eosinophilic cationic Protein (ECP) [ Time Frame: 52 weeks ]
    • Time to clinical response and time to change of baseline parameters of clinical Response: blood periostin [ Time Frame: 52 weeks ]
    • Mean change from baseline in Asthma Control Questionnaire (ACQ) [ Time Frame: 52 weeks ]
    • Mean change from baseline in Asthma Quality of Life Questionnaire (AQLQ) [ Time Frame: 52 weeks ]
    • Mean change from baseline in St. George´s Respiratory Questionnaire (SQRG) [ Time Frame: 52 weeks ]
    • Mean change from baseline in Dyspnoe Index (BDI/TDI) [ Time Frame: 52 weeks ]
    • Mean change from baseline in fatique [ Time Frame: 52 weeks ]
    • Mean change from baseline in number of days off school/work over the 48-week treatment period [ Time Frame: 48 weeks ]
    • Time to first clinically significant exacerbation requiring oral or systemic corticosteroids, hospitalization, and/or emergency department (ED) visits [ Time Frame: 52 weeks ]
      • <

      Original Secondary Outcome: Same as current

      Information By: Johannes Gutenberg University Mainz

      Dates:
      Date Received: August 31, 2015
      Date Started: November 17, 2015
      Date Completion: August 2017
      Last Updated: April 28, 2017
      Last Verified: April 2017