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

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.

Study Overview

• Status: Recruiting
• Conditions: Asthma
• Intervention / Treatment: Biological: Mepolizumab; Drug: Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: David Aronsson; Phone Number: +4646171234; Email: david.aronsson@skane.se
• Study Contact Backup: Name: Leif Bjermer; Phone Number: +46462325; Email: leif.bjermer@med.lu.se

Study Locations

• Sweden
  • Skane
    • Lund, Skane, Sweden, 22185
      • Recruiting
      • The Lung and Allergy Clinic, Skåne University Hospital (SUS)
      • Contact: David Aronsson; Phone Number: +4646171234; Email: david.aronsson@skane.se
      • Contact: Ellen Tufvesson; Phone Number: +46736401916; Email: ellen.tufvesson@med.lu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All asthma patients will be recruited at the Department of Allergology and Lung Medicine, Skåne University Hospital (SUS), Lund, Sweden. Healthy control subjects are recruited by local advertisement.

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Asthma patients initiating Mepolizumab treatment; Patients will be selected on the standard criteria used to select eligible asthma patients for mepolizumab treatment (i.e. patients with eosinophilic asthma that are not controlled by conventional high dose ICS and LABA etc). All eligible asthma patients may be included. Exclusion criteria: any infection	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); Other Names: Mepolizumab (brand name: Nucala); 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); Other Names: ICS and LABA
Asthma patients already on Mepolizumab treatment; Patients that have been selected and given Mepolizumab treatment for > 4 months according to standard eligible and treatment regimen criteria (i.e. patients with eosinophilic asthma that are not controlled by conventional high dose ICS and LABA etc). All eligible asthma patients that have been on Mepolizumab treatment for > 4 weeks will be included. Exclusion criteria: any infections	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); Other Names: Mepolizumab (brand name: Nucala); 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); Other Names: ICS and LABA
Asthma patients without Mepolizumab treatment; Inclusion: Asthma patients without any biological (antibody-based) treatment but on routine ICS and LABA treatment as part of their normal care. Exclusion criteria are any infections	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); Other Names: ICS and LABA
Healthy non-asthmatic control subjects; Exclusion criteria: previous history of lung disease, chronic inflammatory condition, or atopy, or cardiovascular disease. Diagnosed or perceived infection within 3 weeks prior to blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
Change in Forced Vital Capacity (FVC)	Spirometry: Forced Vital Capacity (FVC)	Change from baseline at 4 weeks, and 4 months after initiated biological treatment.
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.

Collaborators and Investigators

• Sponsor: Region Skane
• Collaborators: Lund University
• Investigators: Principal Investigator: Jonas Erjefält, Lund University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2023
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): December 18, 2024

Study Registration Dates

• First Submitted: December 15, 2022
• First Submitted That Met QC Criteria: January 16, 2023
• First Posted (Estimate): January 19, 2023

Study Record Updates

• Last Update Posted (Estimate): January 19, 2023
• Last Update Submitted That Met QC Criteria: January 16, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 1072615

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No