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

This study has been terminated.
(recruitment problems)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02594332
First Posted: November 3, 2015
Last Update Posted: July 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
PD Dr. Stephanie Korn, Johannes Gutenberg University Mainz
  Purpose
The purpose of the MEMORY trial is to compare the effects of mepolizumab with Placebo on airway physiology in patients with eosinophilic asthma

Condition Intervention Phase
Asthma Drug: Mepolizumab Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 MEMORY Study

Resource links provided by NLM:


Further study details as provided by PD Dr. Stephanie Korn, Johannes Gutenberg University Mainz:

Primary Outcome Measures:
  • 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 the mean change from baseline in pre- and post-bronchodilator airway resistance at visit 10 (week 24) and at time of response

  • mean change from baseline in pre- and post-bronchodilator IC 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 inspiratory capacity (IC) at visit 10 (week 24) and at time of response

  • mean change from baseline in pre- and post-bronchodilator CO diffusion capacity 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 CO diffusion capacity at visit 10 (week 24) and at time of response


Secondary Outcome Measures:
  • 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 ]
  • Frequency of clinically significant exacerbations [ Time Frame: 52 weeks ]
  • Time to first exacerbation requiring hospitalization or emergency department (ED) visit [ Time Frame: 52 weeks ]
  • Frequency of exacerbations requiring hospitalization (including intubation and admittance to an intensive care unit (ICU)) or ED visits [ Time Frame: 52 weeks ]
  • GETE rating by physician and patient at time of response and over the 52-week treatment period at pre-specified timepoints (1, 3, 6, 9 and 12 months) [ Time Frame: 1, 3, 6, 9 and 12 month ]
  • Mean change in proportion of patients with nasal polyps, chronic sinusitis and loss of smell and taste [ Time Frame: 52 weeks ]
  • Clinical response to mepolizumab in relation to asthma parameters which potentially predict clinical response [ Time Frame: 52 weeks ]
    Clinical response to mepolizumab in relation to asthma parameters which potentially predict clinical response (age at onset and duration of asthma, prior asthma medication, presence of nasal polyps, sense of smell and taste, allergic sensitization (skin prick test, total and specific IgE against aeroallergens and Staph. aureus enterotoxin), reversibility of airflow obstruction, eNO, blood eosinophils, eosinophilic cationic protein (ECP), blood periostin, ANA, ANCA, ECP.

  • Routine safety assessment (AE and SAE reporting, withdrawals, pregnancy, hematological and clinical chemistry parameters, ECG and vital signs (pulse rate and systolic and diastolic blood pressure)) [ Time Frame: 52 weeks ]
    Routine safety assessments are incorporated throughout and/or at the end of treatment period including AE and SAE reporting, withdrawals, pregnancy, hematological and clinical chemistry parameters, ECG and vital signs (pulse rate and systolic and diastolic blood pressure).


Enrollment: 29
Actual Study Start Date: November 17, 2015
Study Completion Date: May 22, 2017
Primary Completion Date: May 22, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mepolizumab
100 mg SC every 4 weeks for 13 injections
Drug: Mepolizumab
100 mg SC every 4 weeks for 13 injections
Experimental: Placebo
Amount of Placebo corresponding to mepolizumab dose SC every 4 weeks for 13 injections
Drug: Placebo

Detailed Description:

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 the proposed trial will contribute to the question how to best define clinical response to mepolizumab.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form.
  2. Male or female patients at least 18 years
  3. Physician-diagnosis of asthma and evidence of asthma as documented by either reversibility of airflow obstruction (FEV1 ≥ 12% or 200 ml) demonstrated at visit 1 or visit 2 .
  4. ICS dose must be ≥ 1000 μg/day BDP or equivalent daily with or without maintenance oral corticosteroids.
  5. Treatment in the past 12 months with an additional controller medication for at least 3 successive months, e.g., long-acting beta-2-agonist (LABA), leukotriene receptor antagonist (LTRA), or theophylline.
  6. Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 < 80% predicted recorded at Visit 1 or < 90% for patients on oral corticosteroids.
  7. An elevated peripheral blood eosinophil level of ≥ 300/µL that is related to asthma or ≥ 150/µL in patients treated with oral corticosteroids as maintenance therapy demonstrated at visit 1 or in the previous 12 months
  8. Confirmed history of two or more exacerbations requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral), in the 12 months prior to visit 1, despite the use of high-dose inhaled corticosteroids. For patients receiving maintenance corticosteroids, the corticosteroid treatment for the exacerbations must have been a two-fold increase or greater in the dose.

Exclusion Criteria:

  1. Current smokers or former smokers with a smoking history of ≥ 10 pack years (number of pack years = (number of cigarettes per day / 20) x number of years smoked). Patients who have not smoked for ≥ 6 months before visit 1 and have < 10 pack years can be included into the study.
  2. Presence of a clinically important lung condition other than asthma. This includes current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
  3. Patients who have received omalizumab [Xolair] within 130 days of Visit 1.
  4. Patients who have received any biological to treat inflammatory disease within 5 half-lives of visit 1
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02594332


Locations
Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Pneumologie
Mainz, Germany, 55131
Sponsors and Collaborators
Johannes Gutenberg University Mainz
GlaxoSmithKline
Investigators
Principal Investigator: Stephanie Korn, MD Johannes Gutenberg University Mainz
  More Information

Responsible Party: PD Dr. Stephanie Korn, principal investigator, Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier: NCT02594332     History of Changes
Other Study ID Numbers: 2015-001
2015-001868-19 ( EudraCT Number )
First Submitted: August 31, 2015
First Posted: November 3, 2015
Last Update Posted: July 13, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by PD Dr. Stephanie Korn, Johannes Gutenberg University Mainz:
eosinophilic asthma
mepolizumab
treatment

Additional relevant MeSH terms:
Asthma
Pulmonary Eosinophilia
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Hypereosinophilic Syndrome
Eosinophilia
Leukocyte Disorders
Hematologic Diseases