Characteristics of Type 2- High Inflammatory Endotype of Asthma Using New Biomarkers From Peripheral Blood and Exhaled Air and Its Effect on the Outcome of Therapy

Sponsor

Value Outcomes Ltd. (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05270278

Collaborator

AstraZeneca (Industry)

Enrollment

Location

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this study is to identify reliable, valid, easily measurable, interpretable, and useful biomarkers in peripheral blood and exhaled air by people with severe asthma for a more accurate description of the pathogenetic processes of asthma-related to the inflammatory endotype and the choice of biologic therapy.

Condition or Disease	Intervention/Treatment	Phase
Asthma; Eosinophilic Asthma Chronic Bronchial Asthma Asthma, Bronchial

Detailed Description

According to WHO, asthma bronchiale (AB) is the most frequent non-infectious disease in adults. There are 340 million patients with AB in the world. Approximately 500 000 patients in the Czech Republic are suffering from AB and 2,1 % have severe AB with the indication for conventional anti-inflammatory treatment. This subgroup of patients represents significantly high costs for the healthcare system.

There are many clinical phenotypes and molecular endotypes of AB and each of these groups has a different response to treatment. In the Czech republic is recommended classification into two main groups: eosinophil AB (type 2- high) and non-eosinophil AB (type 2- low). Eosinophil AB is furthered classified into two groups: eosinophil allergic (Th2-high) and eosinophil non-allergic (ILC2-high).

New biologicals, indicated for patients with the most severe form of AB, have entered the market during the last 15 years. These biologicals have confirmed their potential in randomized controlled studies. It can be assumed that there are 4 000 - 5000 patients suffering from this type of AB who could be indicated to this treatment in the Czech republic but, unfortunately, only 10 % of them have the access to such therapies in real practice.

Recommended markers of type 2- high AB don´t have strictly set critical values that are often unspecific, unstable in time, and often affected by other diseases or treatments. Some of the widely accepted predictors of response to biological treatment are eosinophilia, allergic reactivity, level of total and allergic-specific IgE, NO production in inhaled air (FeNO), gender, number of previous exacerbations, and duration of disease. Some of these predictors are used as decision criteria also in Global Initiative for Asthma (GINA) guidelines.

With respect to these facts, enormous efforts are being made worldwide to search for new biomarkers, which would be reliable, valid, easily measurable, interpretable, and useful for a more accurate description of the pathogenetic processes of asthma

Study Design

Study Type:

Observational

Anticipated Enrollment :

80 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

Characteristics of Type 2- High Inflammatory Endotype of Asthma Using New Biomarkers From Peripheral Blood and Exhaled Air and Its Effect on the Outcome of Therapy

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
1. Eosinophilic AB - initiated biological treatment against IL-5 or IL-5R initiated biological treatment - mepolizumab or benralizumab judged by the treating physician, the patient cannot indicated treatment of type anti IgE or anti IL-4R
2. Eosinophilic AB - initiated biological treatment against IgE or IL-4R initiated biological treatment - omalizumab or dupilumab judged by the treating physician, patient cannot indicated treatment type anti IL-5 or anti IL-5R
3. Eosinophilic AB - initiated biological treatment against IgE or IL-4R, or against IL-5 or IL-5R initiated biological treatment - omalizumab or dupilumab, or mepolizumab or benralizumab judged by the treating physician, the patient could be potentially indicated to treatment with all 4 alternatives
4. Non-eosinophilic AB - without indication for biological treatment no biological treatment initiated judged by the treating physician, the patient cannot be indicated to biological treatment

Outcome Measures

Primary Outcome Measures

Laboratory parameters (peripheral blood) - blood count [Baseline]
Laboratory parameters (peripheral blood) - atopy [Baseline]
Laboratory parameters (peripheral blood) - rheumatology [Baseline]
ANF, ENA, RF, ANCA (if not in the last 12 months)
Laboratory parameters (peripheral blood) - immunology [Baseline]
IgE, ECP, IgG, IgA, IgM, classes IgG
Laboratory parameters (peripheral blood) - flow cytometry (FACS) [Baseline]
The evaluation of eosinophil surface charakteristics per MFI
Clinical parameters (exhaled air) - FeNO [Baseline]
Clinical parameters (exhaled air) - alveolar NO [Baseline]
Clinical parameters (exhaled air) - eNOSE [Baseline]
The examination with "the electronical nose"

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Group 1 <

Inclusion Criteria:

severe persistent eosinophilic AB (type 2- high)
initiated biological treatment against IL-5 or IL-5R (mepolizumab, benralizumab) on this study visit
judged by the treating physician, the patient cannot be indicated to treatment against anti IgE or anti IL-4R (omalizumab, dupilumab)
signed informed consent
signed consent to the processing of personal data
willingness and ability to undergo examination

Exclusion Criteria:

active smoker
BMI higher than 40kg/m2
ongoing oncological disease or oncological disease during the last 12 months
severe cardiovascular disease
uncontrolled diabetes mellitus
contraindication of choosen biological treatment per SPC
Group 2 <

Inclusion Criteria:

severe persistent eosinophil AB (type 2- high)
initiated biological treatment against IgE or IL-4R (omalizumab, dupilumab) at this study visit
judged by the treating physician, a patient cannot be indicated to treatment against anti IL-5 or anti IL-5R (mepolizumab, benralizumab)
signed informed consent
signed consent to the processing of personal data
willingness and ability to undergo examination

Exclusion Criteria:

active smoker
BMI higher than 40kg/m2
ongoing oncological disease or oncological disease during the last 12 months
severe cardiovascular disease
uncontrolled diabetes mellitus
contraindication of choosen biological treatment per SPC
Group 3 <

Inclusion Criteria:

severe persistent eosinophil AB (type 2- high)
initiated biological treatment against IgE or IL-4R (omalizumab, dupilumab) or against IL-5 or IL-5R (mepolizumab, benralizumab) at this study visit was
judged by the treating physician, the patient could be potentially indicated to treatment with all 4 alternatives
signed informed consent
signed consent to the processing of personal data
willingness and ability to undergo examination

Exclusion Criteria:

active smoker
BMI higher than 40kg/m2
ongoing oncological disease or oncological disease during the last 12 months
severe cardiovascular disease
uncontrolled diabetes mellitus
contraindication of choosen biological treatment per SPC
Group 4 <

Inclusion Criteria:

severe persistent non-eosinophil AB (type 2- low)
judged by the treating physician, the patient cannot be indicated for biological treatment
signed informed consent
signed consent to the processing of personal data
willingness and ability to undergo examination