BASEAS: Interaction Between Benralizumab and Basophils in Eosinophilic Asthma

Sponsor

Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04742504

Collaborator

(none)

Enrollment

17.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

In this study, investigators want to evaluation of the impact of benralizumab (Fasenra®, Astra Zeneca) on different cell populations, including basophils and innate lymphoid cells, and several biomarkers, such as miRNAs, cadena α dek receptor pra la interleukin % (IL5Rα) and soluble IL5Rα in patients with severe eosinophilic asthma. For this, basophil and innate cells type 2 (ILC2) populations will be monitored in different point-time of treatment: 8 week (V1), 6 months (V2) and 1 year (V3) in blood and sputum samples. Also, follow-up IL5Rα expression on a cell surface of eosinophils, basophils and ILC2 from peripheral blood and sputum of patients treated with or or without benralizumab. Determination of IL5Rα levels will be performed by flow cytometry

Condition or Disease	Intervention/Treatment	Phase
Asthma; Eosinophilic	Biological: BENRALIZUMAB

Detailed Description

For this:

Investigators will monitor basophil miRNAs changes with benralizumab analyzing miRNAS profile of isolated basophil before and after benralizumab treatment.
Also, in vitro characterization of benralizumab effects on functionality of human basophils (isolated from allergic asthmatic patients) and human cell line KU812, measuring apoptosis, activation, degranulation and histamine release will be performed.

Study Design

Study Type:

Observational

Anticipated Enrollment :

20 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Interaction Between Benralizumab and Basophils in Eosinophilic Asthma. Discovering a New Role of an Old Asthma Player: BASEAS STUDY (Basophils in Eosinophilic Asthma)

Anticipated Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
BENRA Treated Patients Patients with severe eosinophilic asthma who will be treated with benralizumab (Fasenra®, Astra Zeneca) will be able to participate in a volunteer manner in the study after sing informed consent.	Biological: BENRALIZUMAB The decision of the patients treatment with benralizumab (Fasenra®, Astra Zeneca) included in the study will not come in any case influenced by their participation in the study but will be made in accordance with the clinical criteria established by the Asthma Multidisciplinary Unit (UMA).
Non BENRA TREATED PATIENTSP patients with controlled severe asthma requiring high-dose inhaled corticosteroids plus long-acting beta agonists (with or without oral corticosteroids) but without request of benralizumab (Fasenra®, Astra Zeneca) treatment will be recruited

Arm

Intervention/Treatment

BENRA Treated Patients

Patients with severe eosinophilic asthma who will be treated with benralizumab (Fasenra®, Astra Zeneca) will be able to participate in a volunteer manner in the study after sing informed consent.

Biological: BENRALIZUMAB

The decision of the patients treatment with benralizumab (Fasenra®, Astra Zeneca) included in the study will not come in any case influenced by their participation in the study but will be made in accordance with the clinical criteria established by the Asthma Multidisciplinary Unit (UMA).

Non BENRA TREATED PATIENTSP

patients with controlled severe asthma requiring high-dose inhaled corticosteroids plus long-acting beta agonists (with or without oral corticosteroids) but without request of benralizumab (Fasenra®, Astra Zeneca) treatment will be recruited

Outcome Measures

Primary Outcome Measures

Fold changes in number of basophils [From 1 to 12 months]
Fold changes in number of basophils after 8 week, 6 months and 1 year of benralizumab treatment (Fasenra®, Astra Zeneca) in blood and sputum in patients with severe eosinophilic asthma
Fold changes in number of innate inmmune cells [From 1 to 12 months]
Fold changes in number of innate immune cells s after 8 week, 6 months and 1 year of benralizumab treatment (Fasenra®, Astra Zeneca) in blood and sputum in patients with severe eosinophilic asthma
The fold changes of IL-5R expression in basophils [From 1 to 12 months]
The fold changes of IL-5R expression in basophils after 8 week, 6 months and 1 year of benralizumab treatmen
The fold changes of f IL-5R expression in innate lymphoid cells [From 1 to 12 months]
The fold changes of f IL-5R expression in innate lymphoid cells after 8 week, 6 months and 1 year of benralizumab treatment

Secondary Outcome Measures

Fold changes of miRNAs profile in basophils [From 6 to 18]
1. Fold changes of miRNAs profile in basophils after tratment of Benralizumab in in patients with severe eosinophilic asthma treatment.
Fold changes of serum IL-5R [Fromm 6 to 12]
Fold changes of serum IL-5R (microg/ml) in patients treated with benralizumab
Effect of benralizumab in basophil apoptosis [From 12 to 24 months]
The effect of benralizumab in basophil apoptosis isolated from from allergic asthmatic patients will be measure by fold change of annexin V
Effect of benralizumab in KU812 apoptosis [From 12 to 24 months]
The effect of benralizumab in KU812 apoptosis will be measure by fold change of annexin V in KU812 cultures
Effect of benralizumab in basophil activation [From 12 to 24 months]
The effect of benralizumab in basophil activation isolated from from allergic asthmatic patients will be measur by fold change of CD63, and CD203C on membrane by flow cytometry
Effect of benralizumab in KU812 activation [From 12 to 24 months]
The effect of benralizumab in KU812 activation will be measurie by fold change of CD63, and CD203C on membrane by flow cytometry
Effect of benralizumab in basophil degranulation [From 12 to 24 months]
The effect of benralizumab in basophil degranulation will be measure by histamine releasing in isolated basophils from from allergic asthmatic patients
Effect of benralizumab in KU812 degranulation [From 12 to 24 months]
The effect of benralizumab in basophil degranulation will be measure by histamine releasing in KU812 cultured cells

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

.It is mandatory that all patients can comprehend the study requirements and provide informed consent for their participation in MEGA.

Group A:

Adult people (≥ 18 and ≤ 80 years old) with eosinophilic severe asthma requiring high-dose inhaled corticosteroids plus long-acting beta agonists (with or without long-acting muscarinic antagonist or Montelukast or oral corticosteroids)
Benralizumab treatment approved.

Group B:

.Patients with allergic asthma (prick test or RAST positive).

Exclusion Criteria:

Patients with continuous OCS treatment
Patients with Immunosuppressive drugs
Patients with primary or secondary immune deficiency,
Patients with chronic or/and concomitant disease, presence of severe systemic disease or cancer,
Patients with possible infestation by parasites.
Patients with other acute or chronic active lung disorders Patients with significant psychiatric disorders
Patients with biological treatment will be excludes for group B