Interaction Between Benralizumab and Basophils in Eosinophilic Asthma (BASEAS)

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

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

Study Overview

• Status: Completed
• Conditions: Asthma; Eosinophilic
• Intervention / Treatment: Biological: BENRALIZUMAB

Detailed Description

For this:

1. Investigators will monitor basophil miRNAs changes with benralizumab analyzing miRNAS profile of isolated basophil before and after benralizumab treatment.
2. 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 Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain
    • Instituto Investigación FJD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Group A: f patients with severe eosinophilic uncontrolled asthma treated with Benralizumab Those will be patients with severe eosinophilic asthma who are being treated with benralizumab and who want to participate in a volunteer manner in the study after signing informed consent. The decision of the patients treatment with benralizumab 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).

Group B:patients with allergic asthma without indication of treatment with biological therapy.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fold changes in number of basophils	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	From 1 to 12 months
Fold changes in number of innate inmmune cells	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	From 1 to 12 months
The fold changes of IL-5R expression in basophils	The fold changes of IL-5R expression in basophils after 8 week, 6 months and 1 year of benralizumab treatmen	From 1 to 12 months
The fold changes of f IL-5R expression in innate lymphoid cells	The fold changes of f IL-5R expression in innate lymphoid cells after 8 week, 6 months and 1 year of benralizumab treatment	From 1 to 12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
• Investigators: Principal Investigator: VICTORIA DEL POZO, PhD, IIS-FUNDACIÓN JIMENEZ DIAZ

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2021
• Primary Completion (Actual): October 1, 2023
• Study Completion (Actual): October 13, 2023

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: February 2, 2021
• First Posted (Actual): February 8, 2021

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 13, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: microRNAs; Asthma; Benralizumab; Basophils; anti-receptor de interleukin 5
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Leukocyte Disorders; Eosinophilia; Hypereosinophilic Syndrome; Asthma; Pulmonary Eosinophilia; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: ESR-20-20764

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No