Blood Leukocyte Profiling in Eosinophilic Type 2 Asthma: Influence of Systemic IL-5 Targeting

Asthma Clinical Trial

Official title:

Blood Leukocyte Profiling in Eosinophilic Type 2 Asthma: Influence of Systemic IL-5 Targeting

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05689931
• Other study ID #: 1072615
• Status: Recruiting
• Start date: February 1, 2023
• Est. completion date: December 18, 2024

Study information

• Verified date: November 2022
• Source: Region Skane
• Contact: David Aronsson
• Phone: +4646171234
• Email: david.aronsson[@]skane.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this exploratory and observational prospective study is to study the composition and phenotypes of blood leukocytes collected from asthmatic patients before and after instantiated treatment with the interleukin-5 neutralizing antibody mepolizumab. Comparisons will be made to leukocyte profiles in patients already on mepolizumab treatment, asthma patients without any biological treatment, and non-diseased control subjects.

Description:

Asthma is a chronic inflammatory and obstructive condition affecting the airways. The disease is commonly associated with elevated blood eosinophils and tissue eosinophilia. Many aspects of the pathophysiological mechanisms and clinical symptoms are controlled by conventional therapies such as inhaled corticosteroids (ICS) and long acting β2 agonists. However, some patients remain clinically uncontrolled and need additional treatment such as direct targeting of eosinophil granulocytes by neutralizing the eosinophil-promoting cytokine interleukin 5 (IL5). Mepolizumab is a humanized monoclonal IL-5 neutralizing antibody that is used to treat patients with moderate-severe eosinophilic asthma. While a marked reduction of eosinophils is a key effect of mepolizumab, the exact mechanism of action is unknown. Apart from basophils, that also express the receptor for IL-5, other leukocytes are likely to be indirectly affected by the suppressed eosinophilia. In addition, it is largely unknown to what extent the few eosinophils remaining after anti-IL5 treatment differ from pre-treatment eosinophils. The present study is a prospective observational asthma study that aims to use microscopic analysis to investigate the composition and subtypes of blood leukocytes collected before and after instantiated mepolizumab treatment. Comparisons are made to patients already on mepolizumab treatment, asthma patients without any biological treatment, and non-diseased control subjects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 18, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of asthma (the asthma patient arms)
• Eligible for Mepolizumab treatment as per the country-specific prescribing information (the arms with Mepolizumab)

Exclusion criteria:

• Any diagnosed infection (all arms)
• Previous history of lung disease, chronic inflammatory condition, atopy, or cardiovascular disease. Diagnosed or perceived infection within 3 weeks prior to blood sampling (Healthy non-asthma control subjects)

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Mepolizumab
Mepolizumab is administered by subcutaneous injection with guideline recommended patient selection and dosing for treatment of eosinophilic asthma. Accordingly, the Mepolizumab treatment is given as add-on therapy to standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)

Drug:
• Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Routine asthma treatment with inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)

Locations

Country	Name	City	State
Sweden	The Lung and Allergy Clinic, Skåne University Hospital (SUS)	Lund	Skane

Sponsors (2)

Lead Sponsor	Collaborator
Region Skane	Lund University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Forced Expiratory Volume in 1 second (FEV1)	Spirometry: Forced Expiratory Volume, 1s; (FEV1).	Change from baseline at 4 weeks, and 4 months after initiated biological treatment.
Other	Change in Forced Vital Capacity (FVC)	Spirometry: Forced Vital Capacity (FVC)	Change from baseline at 4 weeks, and 4 months after initiated biological treatment.
Other	Change in Exhaled FeNo	Fractional exhaled NO will be measured at multiple flows	Before and 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment.
Primary	Change in Blood Eosinophil Marker Expression	Quantitative immunohistochemical analysis of eosinophil marker expression in blood leukocyte pellets	Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
Primary	Change in Blood Basophil Marker Expression	Quantitative immunohistochemical analysis of basophil marker expression in blood leukocyte pellets	Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
Primary	Change in Blood Leukocyte Composition	Immunohistochemical determination of the relative proportion (percent) of the leukocyte populations in blood leukocyte pellets	Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
Secondary	Change in Blood T Lymphocyte Marker Expression	Quantitative immunohistochemical analysis of T lymphocyte marker expression in paraffin-embedded blood leukocyte pellets	Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
Secondary	Change in Blood B Lymphocyte Marker Expression	Quantitative immunohistochemical analysis of T lymphocyte marker expression in paraffin-embedded blood leukocyte pellets	Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
Secondary	Leukocyte Total Cell Counts	Routine hemacytometer total leukocyte cell counts	Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment