A Pragmatic Study to Investigate the Efficacy and Safety of Mepolizumab in Severe Uncontrolled Asthma in Brazil

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.

Study Overview

• Status: Unknown
• Conditions: Eosinophilic Asthma
• Intervention / Treatment: Drug: Mepolizumab 100 MG [Nucala]

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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Rodrigo A Athanazio, MD, PhD; Phone Number: 5685 +551126615000; Email: rathanazio@yahoo.com.br
• Study Contact Backup: Name: Luciana Cassimiro; Phone Number: +551126615109; Email: luciana.cassimiro@incor.usp.br

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 05403-900
      • Recruiting
      • University of Sao Paulo
      • Contact: Rodrigo Athanazio; Phone Number: 5685 +55 11 2661-5000; Email: rathanazio@yahoo.com.br

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mepolizumab; Mepolizumab 100mg, SC, every 4 weeks	Drug: Mepolizumab 100 MG [Nucala]; Mepolizumab 100mg, SC, every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total score of Saint George's Respiratory Questionnaire (SGRQ) between Week 0 and Week 48	This scales varies from 0 to 100. Higher values means worse quality of life.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	significant exacerbations are definied as those requiring at least 3 days of systemic corticosteroids	48 weeks
Change in lung function (Forced expiratory volume in first second - FEV1)	Measured by spirometry	48 weeks
Change of asthma control measured by Asthma control questionnaire (ACQ) 5	ACQ varies from 0 to 5 with higher values meaning worse asthma control.	48 weeks
Safety measured by the number of adverse events	number of all adverse events	48 weeks
Change of asthma control measured by Asthma Control Test (ACT)	ACT varies from 5 to 25 with higher values meaning better asthma control.	48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of small airway involvement measured by forced oscillometry technique (R5-R20)	Measured by forced oscillometry technique	48 weeks
Change of quality of life measured by Asthma Quality of Life Questionnaire (AQLQ)	Scores range 1-7, with higher scores indicating better quality of life.	48 weeks
Change of airway inflammation measured by fraction of exhaled nitric oxide (FeNO)	Higher levels of FeNO means higher inflammation in the airways	48 weeks
Change of airway inflammation measured by percentage of eosinophils in induced sputum	Higher values of sputum eosinophils means higher inflammation in the airways	48 weeks

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2020
• Primary Completion (Anticipated): January 9, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: January 8, 2020
• First Submitted That Met QC Criteria: January 13, 2020
• First Posted (Actual): January 14, 2020

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: mepolizumab; severe asthma; anti IL-5 monoclonal antibody; pragmatic study
• 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: SDC 4863/19/082; ISS 212936 (Other Grant/Funding Number: GSK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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