Effects of Mepolizumab Compared to Placebo on Airway Physiology in Patients With Eosinophilic Asthma: MEMORY Study (MEMORY)
11 de julio de 2017 actualizado por: 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
Descripción general del estudio
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Actual)
29
Fase
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Mainz, Alemania, 55131
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Pneumologie
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: 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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Experimental: Placebo
Amount of Placebo corresponding to mepolizumab dose SC every 4 weeks for 13 injections
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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mean change from baseline in pre- and post-bronchodilator FVC at visit 10 (week 24) and at time of response
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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®)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 52 weeks
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52 weeks
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Mean change from baseline in Asthma Control Questionnaire (ACQ)
Periodo de tiempo: 52 weeks
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52 weeks
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Mean change from baseline in Asthma Quality of Life Questionnaire (AQLQ)
Periodo de tiempo: 52 weeks
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52 weeks
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Mean change from baseline in St. George´s Respiratory Questionnaire (SQRG)
Periodo de tiempo: 52 weeks
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52 weeks
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Mean change from baseline in Dyspnoe Index (BDI/TDI)
Periodo de tiempo: 52 weeks
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52 weeks
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Mean change from baseline in fatique
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 52 weeks
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52 weeks
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Frequency of clinically significant exacerbations
Periodo de tiempo: 52 weeks
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52 weeks
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Time to first exacerbation requiring hospitalization or emergency department (ED) visit
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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))
Periodo de tiempo: 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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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Stephanie Korn, MD, Johannes Gutenberg University Mainz
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
17 de noviembre de 2015
Finalización primaria (Actual)
22 de mayo de 2017
Finalización del estudio (Actual)
22 de mayo de 2017
Fechas de registro del estudio
Enviado por primera vez
31 de agosto de 2015
Primero enviado que cumplió con los criterios de control de calidad
2 de noviembre de 2015
Publicado por primera vez (Estimar)
3 de noviembre de 2015
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
13 de julio de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
11 de julio de 2017
Última verificación
1 de julio de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades de las vías respiratorias
- Enfermedades del sistema inmunológico
- Enfermedades pulmonares
- Hipersensibilidad, Inmediata
- Enfermedades hematológicas
- Enfermedades bronquiales
- Enfermedades Pulmonares Obstructivas
- Hipersensibilidad Respiratoria
- Hipersensibilidad
- Trastornos de los leucocitos
- Eosinofilia
- Síndrome hipereosinofílico
- Asma
- Eosinofilia pulmonar
Otros números de identificación del estudio
- 2015-001
- 2015-001868-19 (Número EudraCT)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
INDECISO
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .