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

NCT ID: NCT05689931

Last Updated: 2023-01-19

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-01
• Study Completion Date: 2024-12-18

Brief 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.

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.

Conditions

Asthma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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

Mepolizumab

Intervention Type: BIOLOGICAL

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)

Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)

Intervention Type: DRUG

Routine asthma treatment with inhaled corticosteroids (ICS) and long-acting beta 2 agonists (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

Mepolizumab

Intervention Type: BIOLOGICAL

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)

Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)

Intervention Type: DRUG

Routine asthma treatment with inhaled corticosteroids (ICS) and long-acting beta 2 agonists (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

Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)

Intervention Type: DRUG

Routine asthma treatment with inhaled corticosteroids (ICS) and long-acting beta 2 agonists (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

No interventions assigned to this group

Interventions

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)

Intervention Type: BIOLOGICAL

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)

Intervention Type: DRUG

Other Intervention Names

Mepolizumab (brand name: Nucala); ICS and LABA

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Lund University

OTHER

Sponsor Role: collaborator

Region Skane

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonas Erjefält

Role: PRINCIPAL_INVESTIGATOR

Lund University Hospital

Locations

The Lung and Allergy Clinic, Skåne University Hospital (SUS)

Lund, Skåne County, Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

David Aronsson

Role: CONTACT

david.aronsson@skane.se

+4646171234

Leif Bjermer

Role: CONTACT

leif.bjermer@med.lu.se

+46462325

Facility Contacts

David Aronsson

Role: primary

david.aronsson@skane.se

+4646171234

Ellen Tufvesson

Role: backup

ellen.tufvesson@med.lu.se

+46736401916

Other Identifiers

1072615

Identifier Type: -

Identifier Source: org_study_id