Clinical trial NCT05689931: Blood Leukocyte Profiling in Eosinophilic Type 2 Asthma: Influence of Systemic IL-5 Targeting
Official title: Blood Leukocyte Profiling in Eosinophilic Type 2 Asthma: Influence of Systemic IL-5 Targeting
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Asthma
Lead sponsor: Region Skane
Sponsor class: OTHER
Collaborators: name: Lund University
First posted: 2023-01-19
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

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.

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)

Primary outcomes:
measure: Change in Blood Eosinophil Marker Expression
timeFrame: Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
measure: Change in Blood Basophil Marker Expression
timeFrame: Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
measure: Change in Blood Leukocyte Composition
timeFrame: Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
Secondary outcomes:
measure: Change in Blood T Lymphocyte Marker Expression
timeFrame: Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
measure: Change in Blood B Lymphocyte Marker Expression
timeFrame: Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
measure: Leukocyte Total Cell Counts
timeFrame: Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
Other outcomes:
measure: Change in Forced Expiratory Volume in 1 second (FEV1)
timeFrame: Change from baseline at 4 weeks, and 4 months after initiated biological treatment.
measure: Change in Forced Vital Capacity (FVC)
timeFrame: Change from baseline at 4 weeks, and 4 months after initiated biological treatment.
measure: Change in Exhaled FeNo
timeFrame: Before and 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment.
Locations:
city: Lund
country: Sweden
facility: The Lung and Allergy Clinic, Skåne University Hospital (SUS)
state: Skane
Study officials:
affiliation: Lund University Hospital
name: Jonas Erjefält
role: PRINCIPAL_INVESTIGATOR
References: