Effect of Mepolizumab on Decrease of Systemic Corticosteroids in Patients With Severe Eosinophilic Asthma (Mepolizumab)

Effet du Mepolizumab Sur la décroissance de la corticothérapie systémique Chez Des Patients Avec un Asthme éosinophilique sévère Etude Observationnelle, Suivi de Cohorte Via Une ATU Nominative

The primary objective of the study is to measure the effect of mepolizumab on declines in oral corticosteroid therapy (prednisolone or prednisone) in patients with severe eosinophilic asthma.

Asthma is a chronic inflammatory disease of the airways that affects 5 to 10% of adults and children. Despite current treatments that are often effective, 10% of patients are not controlled by inhaled therapies. These severe asthma require regular use of systemic corticosteroids in 30 to 40% of cases. In this context, the use of glucocorticoids is associated with many more or less serious adverse effects, but still affecting the patient's quality of life. Several treatments have already been proven to save systemic steroids (theophylline, anti-leukotrienes, golimumab ...). On the other hand, none is currently recommended because of a risk / benefit ratio that is too high.

Mepolizumab is a human monoclonal antibody that binds to and inactivates interleukin 5. It has recently been shown to be effective in reducing the daily dose of oral corticosteroids and in reducing exacerbations in these patients with severe eosinophilic asthma. It also reduces the number of eosinophils in the blood and sputum and improves the quality of life.

Patients will receive a subcutaneous injection of 100mg mepolizumab every 4 weeks for one year, for a total of 12 injections.

In France, this treatment was subject to a Temporary Authorization for Nominative Use in severe eosinophilic asthma and is reserved for hospital use.

The injections will be done in HDJ Pneumology CHU Grenoble Alpes and patients will be followed monthly during injections and one month after the end of injections.

Study Overview

• Status: Completed
• Conditions: Asthma; Eosinophilic
• Intervention / Treatment: Drug: Mepolizumab

• Study Type: Observational
• Enrollment (Actual): 27

Contacts and Locations

Study Locations

• France
  • La Tronche, France, 38700
    • University Hospital Grenoble

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients included are those who have obtained the temporary authorization for nominative use for mepolizumab

Description

Inclusion Criteria:

• Severe eosinophilic asthma
• Patient on inhaled therapy with inhaled corticosteroid and long-acting bronchodilator for at least 6 months
• Patient under oral corticosteroid therapy (prednisolone or prednisone) for at least 6 months and unmodified in the last 4 weeks before the first injection
• Patient able to provide informed and written consent
• Obtaining the temporary authorization for nominative use for mepolizumab

Exclusion Criteria:

• Chronic pulmonary pathology other than asthma
• Active neoplasia
• Active liver disease
• Serious and uncontrolled cardiovascular pathology (LVEF less than 30%, NYHA IV, ...)
• Other eosinophilic pathology (Churg & Strauss syndrome, parasitic infection, ...)
• Hypersensitivity to mepolizumab or excipient
• Immunity disorders
• Patient not affiliated to a social security system

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
mepolizumab; Patients will receive a subcutaneous injection of mepolizumab 100 mg every 4 weeks for one year, for a total of 12 injections	Drug: Mepolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of mepolizumab on declines in oral corticosteroid therapy (prednisolone or prednisone) in patients with severe eosinophilic asthma.	Rate of decrease in systemic corticosteroids between the day of the first injection and one month after the last injection.	13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asthma control	Asthma Control Questionnaire (ACT)	Every month during 13 months
Improving quality of life	Asthma Quality of Life Questionnaire (AQLQ)	Every month during 13 months
Improvement of respiratory functional explorations, Forced Expiratory Volume	Forced Expiratory Volume	Every month during 13 months
Decrease in the number of exacerbations	An exacerbation is defined as an episode of progressive degradation, over a few days, of one or more clinical signs, as well as functional parameters of bronchial obstruction.	Assessed every month during 13 months
Improvement of respiratory functional explorations	Vital Capacity	Every month during 13 months
Improvement of respiratory functional explorations	Forced Vital Capacity	Every month during 13 months
Improvement of respiratory functional explorations	FEV/FVC	Every month during 13 months

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Study Chair: Margaux Isnard, Resident, University Hospital, Grenoble; Study Chair: Laure Geneletti, Resident, University Hospital, Grenoble; Study Chair: Audrey Lehmann, Ph, University Hospital, Grenoble; Study Chair: Pierrick Bedouch, PhD, University Hospital, Grenoble; Study Chair: Sébastien Chanoine, University Hospital, Grenoble

Publications and helpful links

General Publications

• Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1189-97. doi: 10.1056/NEJMoa1403291. Epub 2014 Sep 8.
• Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, Chanez P; MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1198-207. doi: 10.1056/NEJMoa1403290. Epub 2014 Sep 8. Erratum In: N Engl J Med. 2015 Apr 30;372(18):1777.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 25, 2016
• Primary Completion (ACTUAL): October 31, 2017
• Study Completion (ACTUAL): October 31, 2017

Study Registration Dates

• First Submitted: February 26, 2018
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (ACTUAL): March 2, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 3, 2018
• Last Update Submitted That Met QC Criteria: October 1, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: asthma; mepolizumab; corticosteroids
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Leukocyte Disorders; Eosinophilia; Hypereosinophilic Syndrome; Asthma; Pulmonary Eosinophilia
• Other Study ID Numbers: 38RC16.137

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No