Severe Asthma Exacerbations and Mepolizumab Treatment

NCT ID: NCT04914078

Last Updated: 2022-05-18

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 70 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-09-21
• Study Completion Date: 2023-12-01

Brief Summary

This is a hypothesis-generating project to investigate a) infective etiology and b) inflammatory profile of the exacerbations of asthma in severe asthmatic patients treated with the humanized monoclonal antibody against interleukin-5 Mepolizumab. Under these treatment conditions the study will inform on the relationship between these two axes: infection & innate immunity Vs inflammatory profile changes occurring during exacerbation events.

In addition, the study will also explore the effect of Mepolizumab treatment on airway microbial composition and on airway/systemic immune response both at stable state and at the exacerbation.

Detailed Description

Longitudinal, observational study to evaluate the infective etiology and the inflammatory profile of asthma exacerbations in severe asthmatic patients treated (as part of routine medical care) with the humanized monoclonal antibody against interleukin-5 Mepolizumab.

The participants receive Mepolizumab as part of routine medical care (see inclusion criteria). The study will assess the effect of the intervention (Mepolizumab) on airway microbial compositions and on airway/systemic inflammation at exacerbation and at stable state.

The patients will be evaluated at baseline (the day of Mepolizumab initiation, before Mepolizumab administration - V0), at 1 month after Mepolizumab initiation (treatment visit - V1), at exacerbation (exacerbation visit - V2) and at 3 months after the exacerbation event (convalescence visit - V3) up to 12-month study period (Table 1). To perform the convalescence visit, a 3-month extension of the study period will be applied if the exacerbation occurs from month 9 to month 12 from the initiation of Mepolizumab. Recurrent exacerbation events will be evaluated separately when a paired-3-month convalescence visit can be performed within the study period.

The patients will contact the center/researchers in case of worsening of the respiratory symptoms to schedule the exacerbation visit. The visit will be performed within 7 days from the beginning of the deterioration of the symptoms.

At each visit, the following procedures will be performed in all the patients: 1) Clinical/pharmacological assessment (including assessment of asthma control; and measurements of central and peripheral fractional exhaled nitric oxide); 2) lung function tests (including lung volumes evaluation and small airway functional assessment by impulse oscillometry - IOS); 3) blood and sputum differential inflammatory cell counts; 4) sputum samples for microbiological assays (conventional sputum cultures and Multiplex Real Time PCR for virus and bacterial detection); 5) blood and sputum samples for cytokine profiling.

In a representative subgroup of patients (n=30) breath condensate, blood and sputum samples will be performed for: 1) airway microbiome (16S ribosomal RNA Sequencing) evaluation; 2) blood innate immune responses; 3) transcriptomics and proteomics of sputum inflammatory cells; 4) breathomics.

The study has been submitted for approval to the ethics committee, and informed written consent will be obtained from each enrolled subject.

Conditions

Severe Asthma

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Mepolizumab treated patients

Severe eosinophil severe asthmatic patients treated with anti IL-5 monoclonal antibody Mepolizumab

Mepolizumab 100 MG

Intervention Type: DRUG

The patients will treated with subcutaneous Mepolizumab at 100 mg every 30 days. Patients will be recruited among those eligible to Mepolizumab treatment according to the Italian Medicine Agency (AIFA; Agenzia Italiana del Farmaco) guidelines who will accept to participate to the study. In particular inclusion criteria will be: severe (Step 4 and 5 GINA) asthma with at least blood eosinophilic count above 300 cells/mcl at least once in the previous year and ≥150 cells/mcl in the absence of systemic corticosteroid treatment before biological treatment initiation. In addition, one of the following conditions will be required: 1) ≥2 exacerbations in the previous year despite appropriate inhaled treatments or 2) the need for systemic corticosteroids on top of inhaled treatment for at least 6 months in the previous year.

Interventions

Mepolizumab 100 MG

The patients will treated with subcutaneous Mepolizumab at 100 mg every 30 days. Patients will be recruited among those eligible to Mepolizumab treatment according to the Italian Medicine Agency (AIFA; Agenzia Italiana del Farmaco) guidelines who will accept to participate to the study. In particular inclusion criteria will be: severe (Step 4 and 5 GINA) asthma with at least blood eosinophilic count above 300 cells/mcl at least once in the previous year and ≥150 cells/mcl in the absence of systemic corticosteroid treatment before biological treatment initiation. In addition, one of the following conditions will be required: 1) ≥2 exacerbations in the previous year despite appropriate inhaled treatments or 2) the need for systemic corticosteroids on top of inhaled treatment for at least 6 months in the previous year.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• severe asthmatic patients according to GINA document (Step 4 and 5 GINA)
• blood eosinophilic count above 300 cells/mcl at least once in the previous year and ≥150 cells/mcl in the absence of systemic corticosteroid treatment before biological treatment initiation.
• In addition, one of the following conditions will be required: 1) ≥2 exacerbations in the previous year despite appropriate inhaled treatments or 2) the need for systemic corticosteroids on top of inhaled treatment for at least 6 months in the previous year.

Exclusion Criteria

• COPD
• Active smoking
• Chronic interstitial lung diseases
• Systemic corticosteroid/immunosuppressive treatments for concomitant conditions other than asthma

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Università degli Studi di Ferrara

OTHER

Sponsor Role: lead

Responsible Party

Alberto Papi, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Azienda Ospedaliero Universitaria Ferrara

Ferrara, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Marco Contoli, MD

Role: CONTACT

ctm@unife.it

+390532688148

Nicholas Battistini

Role: CONTACT

cemicef@unife.it

Facility Contacts

Marco Contoli, Professor

Role: primary

ctm@unife.it

Other Identifiers

82/2021/Oss/AOUFe - ESAMBIO

Identifier Type: -

Identifier Source: org_study_id