Effects of Mepolizumab Compared to Placebo on Airway Physiology in Patients With Eosinophilic Asthma: MEMORY Study (MEMORY)
2017년 7월 11일 업데이트: PD Dr. Stephanie Korn, Johannes Gutenberg University Mainz
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
The purpose of the MEMORY trial is to compare the effects of mepolizumab with Placebo on airway physiology in patients with eosinophilic asthma
연구 개요
상세 설명
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.
연구 유형
중재적
등록 (실제)
29
단계
- 3단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Mainz, 독일, 55131
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Pneumologie
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- 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.
- Male or female patients at least 18 years
- 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 .
- ICS dose must be ≥ 1000 μg/day BDP or equivalent daily with or without maintenance oral corticosteroids.
- 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.
- Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 < 80% predicted recorded at Visit 1 or < 90% for patients on oral corticosteroids.
- 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
- 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:
- 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.
- 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.
- Patients who have received omalizumab [Xolair] within 130 days of Visit 1.
- Patients who have received any biological to treat inflammatory disease within 5 half-lives of visit 1
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Mepolizumab
100 mg SC every 4 weeks for 13 injections
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100 mg SC every 4 weeks for 13 injections
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실험적: Placebo
Amount of Placebo corresponding to mepolizumab dose SC every 4 weeks for 13 injections
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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mean change from baseline in pre- and post-bronchodilator FVC at visit 10 (week 24) and at time of response
기간: week 24 and time of response
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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
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week 24 and time of response
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mean change from baseline in pre- and post-bronchodilator FEV1 at visit 10 (week 24) and at time of response
기간: week 24 and time of response
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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
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week 24 and time of response
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mean change from baseline in pre- and post-bronchodilator RV at visit 10 (week 24) and at time of response
기간: week 24 and time of response
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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
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week 24 and time of response
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mean change from baseline in pre- and post-bronchodilator TLC at visit 10 (week 24) and at time of response
기간: week 24 and time of response
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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
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week 24 and time of response
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mean change from baseline in pre- and post-bronchodilator airway resistance at visit 10 (week 24) and at time of response
기간: week 24 and time of response
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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
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week 24 and time of response
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mean change from baseline in pre- and post-bronchodilator IC at visit 10 (week 24) and at time of response
기간: week 24 and time of response
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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
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week 24 and time of response
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mean change from baseline in pre- and post-bronchodilator CO diffusion capacity at visit 10 (week 24) and at time of response
기간: week 24 and time of response
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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
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week 24 and time of response
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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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)
기간: 1, 3, 6, 9 and 12 months
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1, 3, 6, 9 and 12 months
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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)
기간: 1, 3, 6, 9 and 12 months
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1, 3, 6, 9 and 12 months
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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)
기간: 1, 3, 6, 9 and 12 months
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1, 3, 6, 9 and 12 months
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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)
기간: 1, 3, 6, 9 and 12 months
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1, 3, 6, 9 and 12 months
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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)
기간: 1, 3, 6, 9 and 12 months
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1, 3, 6, 9 and 12 months
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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)
기간: 1, 3, 6, 9 and 12 months
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1, 3, 6, 9 and 12 months
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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)
기간: 1, 3, 6, 9 and 12 months
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1, 3, 6, 9 and 12 months
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Exercise tolerance in a subgroup of patients: Mean change from baseline in exercise endurance time
기간: 1, 3, 6, 9 and 12 month
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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.
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1, 3, 6, 9 and 12 month
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Exercise tolerance in a subgroup of patients: Mean change from baseline in inspiratory capacity (IC)
기간: 1, 3, 6, 9 and 12 month
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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.
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1, 3, 6, 9 and 12 month
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Exercise tolerance in a subgroup of patients: Mean change from baseline in exertional dyspnea and leg discomfort (Borg CR10 Scale®)
기간: 1, 3, 6, 9 and 12 month
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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
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1, 3, 6, 9 and 12 month
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Time to clinical response and time to change of baseline parameters of clinical Response: sence of smell
기간: 52 weeks
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52 weeks
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Time to clinical response and time to change of baseline parameters of clinical Response: sense of taste
기간: 52 weeks
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52 weeks
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Time to clinical response and time to change of baseline parameters of clinical Response: lung volume
기간: 52 weeks
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52 weeks
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Time to clinical response and time to change of baseline parameters of clinical Response: CO Diffusion capacity
기간: 52 weeks
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52 weeks
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Time to clinical response and time to change of baseline parameters of clinical Response: FEV1 reversibility
기간: 52 weeks
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52 weeks
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Time to clinical response and time to change of baseline parameters of clinical Response: exhaled NO (eNO)
기간: 52 weeks
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52 weeks
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Time to clinical response and time to change of baseline parameters of clinical Response: blood eosinophils
기간: 52 weeks
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52 weeks
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Time to clinical response and time to change of baseline parameters of clinical Response: eosinophilic cationic Protein (ECP)
기간: 52 weeks
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52 weeks
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Time to clinical response and time to change of baseline parameters of clinical Response: blood periostin
기간: 52 weeks
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52 weeks
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Mean change from baseline in Asthma Control Questionnaire (ACQ)
기간: 52 weeks
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52 weeks
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Mean change from baseline in Asthma Quality of Life Questionnaire (AQLQ)
기간: 52 weeks
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52 weeks
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Mean change from baseline in St. George´s Respiratory Questionnaire (SQRG)
기간: 52 weeks
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52 weeks
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Mean change from baseline in Dyspnoe Index (BDI/TDI)
기간: 52 weeks
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52 weeks
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Mean change from baseline in fatique
기간: 52 weeks
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52 weeks
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Mean change from baseline in number of days off school/work over the 48-week treatment period
기간: 48 weeks
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48 weeks
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Time to first clinically significant exacerbation requiring oral or systemic corticosteroids, hospitalization, and/or emergency department (ED) visits
기간: 52 weeks
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52 weeks
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Frequency of clinically significant exacerbations
기간: 52 weeks
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52 weeks
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Time to first exacerbation requiring hospitalization or emergency department (ED) visit
기간: 52 weeks
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52 weeks
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Frequency of exacerbations requiring hospitalization (including intubation and admittance to an intensive care unit (ICU)) or ED visits
기간: 52 weeks
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52 weeks
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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)
기간: 1, 3, 6, 9 and 12 month
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1, 3, 6, 9 and 12 month
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Mean change in proportion of patients with nasal polyps, chronic sinusitis and loss of smell and taste
기간: 52 weeks
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52 weeks
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Clinical response to mepolizumab in relation to asthma parameters which potentially predict clinical response
기간: 52 weeks
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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.
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52 weeks
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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))
기간: 52 weeks
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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).
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52 weeks
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
협력자
수사관
- 수석 연구원: Stephanie Korn, MD, Johannes Gutenberg University Mainz
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2015년 11월 17일
기본 완료 (실제)
2017년 5월 22일
연구 완료 (실제)
2017년 5월 22일
연구 등록 날짜
최초 제출
2015년 8월 31일
QC 기준을 충족하는 최초 제출
2015년 11월 2일
처음 게시됨 (추정)
2015년 11월 3일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 7월 13일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 7월 11일
마지막으로 확인됨
2017년 7월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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