Clinical trial NCT03453021: Effect of Mepolizumab on Decrease of Systemic Corticosteroids in Patients With Severe Eosinophilic Asthma
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma; Eosinophilic
Keywords: asthma
mepolizumab
corticosteroids
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2018-03-02
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients included are those who have obtained the temporary authorization for nominative use for mepolizumab

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Effect of mepolizumab on declines in oral corticosteroid therapy (prednisolone or prednisone) in patients with severe eosinophilic asthma.
timeFrame: 13 months
Secondary outcomes:
measure: Asthma control
timeFrame: Every month during 13 months
measure: Improving quality of life
timeFrame: Every month during 13 months
measure: Improvement of respiratory functional explorations, Forced Expiratory Volume
timeFrame: Every month during 13 months
measure: Decrease in the number of exacerbations
timeFrame: Assessed every month during 13 months
measure: Improvement of respiratory functional explorations
timeFrame: Every month during 13 months
measure: Improvement of respiratory functional explorations
timeFrame: Every month during 13 months
measure: Improvement of respiratory functional explorations
timeFrame: Every month during 13 months
Other outcomes:
Locations:
city: La Tronche
country: France
facility: University Hospital Grenoble
Study officials:
affiliation: University Hospital, Grenoble
name: Margaux Isnard, Resident
role: STUDY_CHAIR
affiliation: University Hospital, Grenoble
name: Laure Geneletti, Resident
role: STUDY_CHAIR
affiliation: University Hospital, Grenoble
name: Audrey Lehmann, Ph
role: STUDY_CHAIR
affiliation: University Hospital, Grenoble
name: Pierrick Bedouch, PhD
role: STUDY_CHAIR
affiliation: University Hospital, Grenoble
name: Sébastien Chanoine
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.