The overall aim of the study is to improve personalized medicine for patients with severe asthma through the investigation of possible immunological mechanisms responsible for non-response or incomplete response to biological treatments.2.1 3TR -…
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
3TR-ABC:
To determine super responders, clinical responders, and non-responders of the
real-life severe asthma cohort.
AIR Bio-OCT:
Establish minimal invasive prediction 'signatures' for Benralizumab response in
severe asthma by multilevel non-invasive exhaled breath -omics approach.
Secondary outcome
3TR-ABC:
To identify and describe differences in biomarker profiles between super
responders, clinical responders, and non-responders.
AIR Bio-OCT Study
Establish a change in extra cellular matrix (ECM) and airway smooth muscle mass
(ASM) by standard - PS-OCT and endobronchial biopsy analysis after 52 weeks of
Benralizumab treatment (15 patients).
Background summary
Severe asthma has a large impact on the quality of life of patients and their
families. New biological treatments (eg. Mepolizumab, Benralizumab, Reslizumab,
Dupilumab, Tezepelumab) are currently available to treat severe asthma
patients. However, not all severe asthma patients respond equally to these
treatments and we hypothesize that airway inflammation and remodeling are
pivotal therein, including the reduction in airway smooth muscle (ASM) mass and
extra-cellular matrix (ECM) alterations. Current gold standard techniques to
assess changes in airway remodelling (e.g. high-resolution computed tomography
(HR-CT) of the chest or endobronchial sampling) have their limitations. In this
project we aim: 1) to unravel phenotypes and mechanisms responsible for
insufficient treatment response of biologics, with the ultimate aim to reveal
novel treatment targets in severe asthma patients and 2) to unravel
Benralizumab specific phenotypes and the impact of Benralizumab on airway
remodeling by the use of Optical Coherence Tomography (OCT) in severe asthma
patients.
Study objective
The overall aim of the study is to improve personalized medicine for patients
with severe asthma through the investigation of possible immunological
mechanisms responsible for non-response or incomplete response to biological
treatments.
2.1 3TR - ABC Study objectives
Primary Objective:
• To establish a real-life cohort of patients with severe asthma commenced on a
biological treatment.to determine super responders, clinical responders, and
non-responders
Secondary Objective(s):
• To identify and measure immunologic biomarkers at baseline related to
super-response versus clinical response versus non-response to biological
treatment of severe asthma.
• To identify which pathways that are not suppressed by treatment in
non-responders versus responders (clinical and super).
• To identify and describe differences in biomarker profiles between super
responders, clinical responders, and non-responders at baseline visit.
• To describe differences in changes in biomarker profiles between super
responders, clinical responders, and non-responders.
• To identify the impact of super-, clinical-, and non-response on long-term
outcomes (3 years).
• To identify predictors of persistent response/loss of response to biologic
treatments.
Exploratory Objective(s):
• To network and make cluster analyses of omics data in order to determine
possible novel biomarker signatures and relate these to clinical response.
• To compare and cross-validate known biomarker profiles with those derived
from previously published severe asthma studies.
2.2 AIR-BIO-OCT substudy objectives
Primary Objective:
• To identify and measure an eNose/ volatile organic compound (VOC)-
multi-omics extensive severe asthma phenotyping strategy before treatment with
Benralizumab to reveal add-on response characteristics to better predict
treatment response.
• To identify and measure minimal invasive predicting *signature* of
Benralizumab treatment response in severe eosinophilic asthma by extensive
asthma pheno-endotyping using innovative minimal invasive exhaled breath
technologies including eNose/VOCs and omics.
Secondary Objective(s)
• To measure airway remodeling (extra cellular matrix and airway smooth muscle)
after treatment with Benralizumab
• Establish the reduction of extra cellular matrix (ECM) and airway smooth
muscle (ASM) by standard - polarization sensitive (PS) - OCT and endobronchial
biopsy analyses after 52 weeks of Benralizumab treatment
• To reveal the airway wall delivery and cellular targets of Benralizumab in
vivo by immune-OCT.
Study design
Observational multicenter study, for which the analyses will be done in a
European consortium. Patients will be extensively characterized at baseline and
then followed for 3 years. Data analyses will be performed in an international
research consortium.
Study burden and risks
The burden and risks associated with participation of the study is limited for
all sample collection except for bronchoscopy sampling which is considered
moderate. For this, we have extensive experience with bronchoscopies with
sampling including biopsies and (PS-)OCT imaging in severe asthma patients in
our previous studies including TASMA study. In the future, the results of this
study could lead to improved treatment allocation and novel treatments for
severe asthma patients
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Patients with severe asthma:
Patients with the age of >=18 years diagnosed with severe asthma and eligible
for biologic treatment (in the Netherlands the 3TR- ABC Study will include
patients with severe asthma eligible for Anti-IgE, Anti-IL5(R), and
Anti-IL4/IL13 treatment.).
Patients are defined as having severe asthma if:
* High dose treatment in the last year:
o High dose ICS (corresponding to minimum 1600 micrograms Budesonide per day) +
either LABA, LTRA, or LAMA
or
o Fixed Prednisolone treatment (OCS) minimum 50% of the time.
* Other reasons for lack of control excluded (systematic investigation
according to guidelines for investigation of severe asthma)
and
* Minimum 2 exacerbations in the last year or fixed Prednisolone treatment
(OCS) minimum 50% of the time.
•Clinical decision to initiate Initiation initiate biologic therapy for severe
asthma after meeting licensing, local and national guidelines (Dupilumab,
Mepolizumab, Benralizumab, Tezepelumab, Omalizumab or Reslizumab)
Mild/moderate asthma controls:
Patients of >=18 years with mild/moderate controlled asthma and markers of T2
inflammation (see table 2), or patients with low T2 inflammation, who are not
candidates for biologic treatments.
Healthy controls:
Participants of >=18 years without any history of respiratory symptoms or recent
infections, and who do not use any medication related to airway diseases or are
in treatment for any other diseases that may influence respiratory biomarkers
considerably.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
Severe asthma patients will be excluded if:
* Unable to understand written information due to language barriers.
* Unable to give informed consent, i.e., patients who are incapable.
* Unable to complete study visits.
- Usage of mainetenance OCS (only for patients starting dupiluman, as
part of the Sanofi funded arm, not the overall 3TR)
Exclusion criteria specifically for the AIR-BIo-OCT substudy patiënts:
- Patients have been treated with biologics for severe asthma <3 months before
the inclusion.
- OCS use >20 mg daily.
- BMI >35.
- Have smoked > 15 pack years defined as (number of cigarettes smoked per
day/20) × number of years smoked .
- Reports a diagnosis of EGPA, ABPA or other respiratory condition that
interferes with Benralizumab
Mild/moderate asthma participants will be excluded if:
* Unable to understand written information due to language barriers.
* Unable to give informed consent, i.e., patients who are incapable.
* Show signs of symptoms of uncontrolled asthma (ACQ score higher than 1.5, OCS
use, history of exacerbations within the past year).
Healthy participants will be excluded if:
* Unable to understand written information due to language barriers.
* Unable to give informed consent, i.e., patients who are incapable.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL77983.018.22 |