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

Asthma Clinical Trial

— MEMORY  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02594332
• Other study ID #: 2015-001
• Secondary ID: 2015-001868-19
• Status: Terminated
• Phase: Phase 3
• First received: August 31, 2015
• Last updated: July 11, 2017
• Start date: November 17, 2015
• Est. completion date: May 22, 2017

Study information

• Verified date: July 2017
• Source: Johannes Gutenberg University Mainz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: May 22, 2017
• Est. primary completion date: May 22, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• Pulmonary Eosinophilia

Intervention

Drug:
• Mepolizumab
100 mg SC every 4 weeks for 13 injections
• Placebo

Locations

Country	Name	City	State
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Pneumologie	Mainz

Sponsors (2)

Lead Sponsor	Collaborator
Johannes Gutenberg University Mainz	GlaxoSmithKline

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mean change from baseline in pre- and post-bronchodilator FVC at visit 10 (week 24) and at 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	week 24 and time of response
Primary	mean change from baseline in pre- and post-bronchodilator FEV1 at visit 10 (week 24) and at 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	week 24 and time of response
Primary	mean change from baseline in pre- and post-bronchodilator RV at visit 10 (week 24) and at 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	week 24 and time of response
Primary	mean change from baseline in pre- and post-bronchodilator TLC at visit 10 (week 24) and at 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	week 24 and time of response
Primary	mean change from baseline in pre- and post-bronchodilator airway resistance at visit 10 (week 24) and at 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	week 24 and time of response
Primary	mean change from baseline in pre- and post-bronchodilator IC at visit 10 (week 24) and at 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	week 24 and time of response
Primary	mean change from baseline in pre- and post-bronchodilator CO diffusion capacity at visit 10 (week 24) and at 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	week 24 and time of response
Secondary	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)		1, 3, 6, 9 and 12 months
Secondary	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)		1, 3, 6, 9 and 12 months
Secondary	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)		1, 3, 6, 9 and 12 months
Secondary	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)		1, 3, 6, 9 and 12 months
Secondary	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)		1, 3, 6, 9 and 12 months
Secondary	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)		1, 3, 6, 9 and 12 months
Secondary	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)		1, 3, 6, 9 and 12 months
Secondary	Exercise tolerance in a subgroup of patients: Mean change from baseline in exercise endurance time	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.	1, 3, 6, 9 and 12 month
Secondary	Exercise tolerance in a subgroup of patients: Mean change from baseline in inspiratory capacity (IC)	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.	1, 3, 6, 9 and 12 month
Secondary	Exercise tolerance in a subgroup of patients: Mean change from baseline in exertional dyspnea and leg discomfort (Borg CR10 Scale®)	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	1, 3, 6, 9 and 12 month
Secondary	Time to clinical response and time to change of baseline parameters of clinical Response: sence of smell		52 weeks
Secondary	Time to clinical response and time to change of baseline parameters of clinical Response: sense of taste		52 weeks
Secondary	Time to clinical response and time to change of baseline parameters of clinical Response: lung volume		52 weeks
Secondary	Time to clinical response and time to change of baseline parameters of clinical Response: CO Diffusion capacity		52 weeks
Secondary	Time to clinical response and time to change of baseline parameters of clinical Response: FEV1 reversibility		52 weeks
Secondary	Time to clinical response and time to change of baseline parameters of clinical Response: exhaled NO (eNO)		52 weeks
Secondary	Time to clinical response and time to change of baseline parameters of clinical Response: blood eosinophils		52 weeks
Secondary	Time to clinical response and time to change of baseline parameters of clinical Response: eosinophilic cationic Protein (ECP)		52 weeks
Secondary	Time to clinical response and time to change of baseline parameters of clinical Response: blood periostin		52 weeks
Secondary	Mean change from baseline in Asthma Control Questionnaire (ACQ)		52 weeks
Secondary	Mean change from baseline in Asthma Quality of Life Questionnaire (AQLQ)		52 weeks
Secondary	Mean change from baseline in St. George´s Respiratory Questionnaire (SQRG)		52 weeks
Secondary	Mean change from baseline in Dyspnoe Index (BDI/TDI)		52 weeks
Secondary	Mean change from baseline in fatique		52 weeks
Secondary	Mean change from baseline in number of days off school/work over the 48-week treatment period		48 weeks
Secondary	Time to first clinically significant exacerbation requiring oral or systemic corticosteroids, hospitalization, and/or emergency department (ED) visits		52 weeks
Secondary	Frequency of clinically significant exacerbations		52 weeks
Secondary	Time to first exacerbation requiring hospitalization or emergency department (ED) visit		52 weeks
Secondary	Frequency of exacerbations requiring hospitalization (including intubation and admittance to an intensive care unit (ICU)) or ED visits		52 weeks
Secondary	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)		1, 3, 6, 9 and 12 month
Secondary	Mean change in proportion of patients with nasal polyps, chronic sinusitis and loss of smell and taste		52 weeks
Secondary	Clinical response to mepolizumab in relation to asthma parameters which potentially predict clinical response	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.	52 weeks
Secondary	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))	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).	52 weeks