Clinical trial NCT04228588: A Pragmatic Study to Investigate the Efficacy and Safety of Mepolizumab in Severe Uncontrolled Asthma in Brazil
Official title: A Pragmatic Study to Investigate the Efficacy and Safety of Mepolizumab in Severe Uncontrolled Asthma in Brazil
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Eosinophilic Asthma
Keywords: severe asthma
mepolizumab
anti IL-5 monoclonal antibody
pragmatic study
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2020-01-14
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase IV, single-arm study Number of visits: 13 (W-4, W0, W4, W8, W12, W16, W20, W24, W28, W32, W36, W40, W44, W48) (W = week)
Primary purpose: TREATMENT

Brief summary: The anti-interleukin-5 monoclonal antibody mepolizumab is approved as an add-on therapy in Europe, Canada, USA, and other countries, to standard of care for the treatment of patients with severe eosinophilic asthma. Mepolizumab has been shown to reduce exacerbation rates and dependency on oral corticosteroid use in clinical trials in patients with severe eosinophilic asthma compared with placebo, both in addition to standard of care. Other trials had also showed that treatment with mepolizumab resulted in significant improvements in quality of life (SGRQ) and asthma control (ACQ-5 score) . Mepolizumab has only recently been approved in Brazil. There is still no data regarding its efficacy and safety in the Brazilian population and it is important to emphasize that no Brazilian center participated in the previous large, international and multicentric phase III mepolizumab studies. Therefore, it is crucial to perform a local study in order to validate external results in the Brazilian population.

Detailed description: Severe asthma is associated with substantial morbidity, mortality, health-care costs, and impaired quality of life. Recurrent asthma exacerbations are a major problem in some patients and can predominate in a subgroup with eosinophilic airway inflammation. Mepolizumab is a humanised monoclonal antibody against interleukin 5 that effectively inhibits eosinophilic airway inflammation.

The anti-interleukin-5 monoclonal antibody mepolizumab is approved as an add-on therapy in Europe, Canada, USA, and other countries, to standard of care for the treatment of patients with severe eosinophilic asthma. Mepolizumab has been shown to reduce exacerbation rates and dependency on oral corticosteroid use in clinical trials in patients with severe eosinophilic asthma compared with placebo, both in addition to standard of care. Other trials had also showed that treatment with mepolizumab resulted in significant improvements in quality of life (SGRQ) and asthma control (ACQ-5 score).

Mepolizumab has only recently been approved in Brazil. There is still no data regarding its efficacy and safety in the Brazilian population and it is important to emphasize that no Brazilian center participated in the previous large, international and multicentric phase III mepolizumab studies. Therefore, it is crucial to perform a local study in order to validate external results in the Brazilian population.

Our group belongs to a public academic institution with a focus on assistance, teaching and research. It is a tertiary-referral hospital with an outpatient clinic specializing severe asthma patients. In 2012, the investigators published the first study with the clinical characterization of their cohort of severe asthma and its respective phenotypes. Since then, the investigators have carried out several studies in order to identify prognostic factors and interventions that could improve the control and quality of life of this population. Among them, there are the impact of weight control in asthma symptoms, evaluation of standardized and systematic protocol based on high doses of inhaled corticosteroid plus LABA and 2 weeks course of oral corticosteroids and pathophysiological studies based on bronchial biopsy samples from patients with severe asthma. Since obesity is a serious and prevalent problem in several severe asthma cohorts, another area of interest of the group is to assess the impact of physical activity on this population. Finally, it is important to mention the commitment of the group to evaluate the incorporation of new treatments in the severe asthma population within the Brazilian scenario as done in a specific publication to systematically evaluate the use of omalizumab in our center.

Therefore, the investigators consider that our center has full capacity to conduct a systematic evaluation study of the use of mepolizumab in the population of severe asthma. The investigators aimed to examine the effects of mepolizumab on quality of life, lung function, asthma symptoms and exacerbation rate in patients with severe eosinophilic asthma in a tertiary reference center in Brazil based on real world data.

Eligibility criteria: Inclusion Criteria:

* 18 years or older with severe eosinophilic asthma
* Regular use of high-dose inhaled corticosteroids plus other controller medicines
* Non-controlled asthma characterized by ACQ-5 \> 1.5 OR chronic oral corticosteroids asthmatic patients (Prednisone 5mg or more for at least 3 months) even if ACQ-5 \< 1.5
* History of at least one exacerbation requiring treatment with systemic corticosteroids in the previous 12 months before screening OR chronic oral corticosteroids asthmatic patients (Prednisone 5mg or more for at least 3 months) even without exacerbations
* Blood eosinophil count of at least 300 cells per μL within the 12 months before screening OR a blood eosinophil count of at least 150 cells per μL at screening

Exclusion Criteria:

* Current smokers or former smokers with a history of at least ten pack-years
* Individuals with a concurrent respiratory disease
* Those who had received omalizumab within 30 days before screening
* Patients with severe or clinically significant cardiovascular disease, or other eosinophilic diseases.
* Patients with asthma exacerbation 4 weeks before screening for the study
* Patients with parasitic infection in the 6 months before study entry.
* Patients with substantial uncontrolled comorbidity, possibility of pregnancy
* Patients with history of poor treatment adherence

Primary outcomes:
measure: Change in total score of Saint George's Respiratory Questionnaire (SGRQ) between Week 0 and Week 48
timeFrame: 48 weeks
Secondary outcomes:
measure: Change in the number of clinically significant exacerbations of asthma as defined by: worsening of asthma which requires use of systemic corticosteroids* and/or hospitalisation and/or Emergency Department (ED) visits.
timeFrame: 48 weeks
measure: Change in lung function (Forced expiratory volume in first second - FEV1)
timeFrame: 48 weeks
measure: Change of asthma control measured by Asthma control questionnaire (ACQ) 5
timeFrame: 48 weeks
measure: Safety measured by the number of adverse events
timeFrame: 48 weeks
measure: Change of asthma control measured by Asthma Control Test (ACT)
timeFrame: 48 weeks
Other outcomes:
measure: Change of small airway involvement measured by forced oscillometry technique (R5-R20)
timeFrame: 48 weeks
measure: Change of quality of life measured by Asthma Quality of Life Questionnaire (AQLQ)
timeFrame: 48 weeks
measure: Change of airway inflammation measured by fraction of exhaled nitric oxide (FeNO)
timeFrame: 48 weeks
measure: Change of airway inflammation measured by percentage of eosinophils in induced sputum
timeFrame: 48 weeks
Locations:
city: São Paulo
country: Brazil
facility: University of São Paulo
state: SP
Study officials:
affiliation: Medical Assistant
name: Rodrigo A Athanazio, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: