Severe AsthmaESAM-BIONCT04914078
Severe Asthma Exacerbations and Mepolizumab Treatment
An observational study of Severe Asthma, run by Università degli Studi di Ferrara at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Asthma
- What is being tested?
- Mepolizumab 100 MG
- Type of treatment
- Injection or infusion
- How many people
- 70 participants
- Where
- 1 siteItaly
- Study dates
- 21 Sep 2021to 1 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Severe eosinophils asthmatic patients
Who may be able to join
- 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.
Who cannot join
- COPD
- Active smoking
- Chronic interstitial lung diseases
- Systemic corticosteroid/immunosuppressive treatments for concomitant conditions other than asthma
Trial locations and contacts
1 site in 1 country.
Nicholas Battistini contact
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliero Universitaria Ferrara
Ferrara, 44124
Marco Contoli, Professor, ctm@unife.it
Marco Contoli, Prof
About this study
Official title: Exacerbations of Severe Asthma in Patients Treated With Mepolizumab: Assessment of Biomarkers and Identification of Biologic Clusters
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.
Read the 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
- Being tested
- Mepolizumab 100 MG
- Keywords
- asthma, exacerbations, eosinophils, infections, mepolizumab
- Medical subject headings
- Asthma, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mepolizumab 100 MGDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Mepolizumab treated patients | Severe eosinophil severe asthmatic patients treated with anti IL-5 monoclonal antibody Mepolizumab Receives: Drug: Mepolizumab 100 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inflammation
Co-primary measurements will be: i) changes in blood and sputum eosinophil counts at exacerbation compared to stable state
Measured: 1 year
Infections
Co-primary measurements will be: ii) changes in the frequency of microbial agent detection in sputum samples at exacerbation compared to stable state.
Measured: 1 year
Secondary outcomes (13)
Lung function FEV1 l
FEV1 litre
Measured: 1 year
Lung function FEV1 %
FEV1% predicted
Measured: 1 year
Lung function FVC l
FVC litre
Measured: 1 year
Lung function FVC %
FVC % predicted
Measured: 1 year
Lung function VC l
vital capacity (VC) litre
Measured: 1 year
Lung function VC %
vital capacity (VC) % predicted
Measured: 1 year
Lung function - Impulsed Oscillometry kPa
R5-R20 (kPa/L/s)
Measured: 1 year
Lung function - Impulsed Oscillometry %
R5-R20 % predicted
Measured: 1 year
Asthma control questionnaire (ACT)
Score ranging from 5 to 25
Measured: 1 year
Fractional exhaled nitric oxide (FeNO)
parts per billions (ppb) in the exhaled breath
Measured: 1 year
Sputum Quantitative bacteriology
Serial dilutions (up to 10-12) of sputum samples will be made and cultured on the appropriate media. Colony- forming units (CFU)/mL will be calculated.
Measured: 1 year
Sputum virus profiling
The commercially available multiplex PCR assay RespiFinder RG® (Qiagen) was used according to manufacture instructions for the simultaneous detection and differentiation of 21 respiratory pathogens, including both viruses and atypical bacteria
Measured: 1 year
Cytokines
cytokines profiling (Th1/Th2/Th17 - pg/ml) in blood serum and sputum supernatants will be assessed by by multiplex immunoassay-based (EMD Millipore Burlington, MA, USA)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2021
- Study start21 Sep 2021
- Primary completion1 Sep 2023 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università degli Studi di Ferrara
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Alberto Papi, MD, Università degli Studi di Ferrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04914078
- Sponsor's protocol ID
- 82/2021/Oss/AOUFe - ESAMBIO
- Acronym
- ESAM-BIO
- Status last verified
- May 2022
- First submitted
- 25 May 2021
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exacerbations of Severe Asthma in Patients Treated With Mepolizumab: Assessment of Biomarkers and Identification of Biologic Clusters
- ClinicalTrials.gov ID
- NCT04914078
- Acronym / sponsor ID
- ESAM-BIO / 82/2021/Oss/AOUFe - ESAMBIO
- Conditions
- Severe Asthma
- Keywords
- asthma, exacerbations, eosinophils, infections, mepolizumab
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Università degli Studi di FerraraUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 21 Sep 2021 (actual)
- Primary completion
- 1 Sep 2023 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 4 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mepolizumab treated patients | – | Drug: Mepolizumab 100 MGSevere eosinophil severe asthmatic patients treated with anti IL-5 monoclonal antibody Mepolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Severe eosinophils asthmatic patients
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- COPD
- Active smoking
- Chronic interstitial lung diseases
- Systemic corticosteroid/immunosuppressive treatments for concomitant conditions other than asthma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mepolizumab 100 MGThe 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. | Drug | Mepolizumab treated patients |
Primary outcome
Inflammation
Time frame: 1 year
Co-primary measurements will be: i) changes in blood and sputum eosinophil counts at exacerbation compared to stable state
Infections
Time frame: 1 year
Co-primary measurements will be: ii) changes in the frequency of microbial agent detection in sputum samples at exacerbation compared to stable state.
13 secondary outcomes
Lung function FEV1 l
Time frame: 1 year
Lung function FEV1 %
Time frame: 1 year
Lung function FVC l
Time frame: 1 year
Lung function FVC %
Time frame: 1 year
Lung function VC l
Time frame: 1 year
Lung function VC %
Time frame: 1 year
Lung function - Impulsed Oscillometry kPa
Time frame: 1 year
Lung function - Impulsed Oscillometry %
Time frame: 1 year
Asthma control questionnaire (ACT)
Time frame: 1 year
Fractional exhaled nitric oxide (FeNO)
Time frame: 1 year
Sputum Quantitative bacteriology
Time frame: 1 year
Sputum virus profiling
Time frame: 1 year
Cytokines
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicholas Battistini contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Severe Asthma, run by Università degli Studi di Ferrara at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marco Contoli, MD (+390532688148, ctm@unife.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Inflammation (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2022.