3TR Asthma Biologics Cohort (ABC) Study - A Part of the 3TR (Taxonomy, Treatment, Targets and Remission) Consortium for the Identification of the Molecular Mechanisms of Non-response to Treatment, Relapses, and Remission in Autoimmune, Inflammatory, and Allergic Conditions
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 600
- Locations
- 2
- Primary Endpoint
- No usage of oral corticosteroids in the previous 12 months
Study Overview
Brief Summary
The 3TR-ABC study is a multicentre observational prospective cohort study platform that follows patients with severe asthma from the start of biological therapy and three years onwards. In the 3TR-ABC platform, individual studies are conducted on specific biologics, using aligned study designs. The aim of the study is to assess response to treatment and examine clinical characteristics, biomarkers, and immunological mechanisms related to response, including remission and non-response, that might be new targets or explanations for insufficient treatment. Patients will be extensively characterized at baseline and then followed throughout the years with formal clinical and biological assessment at 4, 16, 52 weeks, and 2, 3 years. Based on the response to treatment, patients will be stratified into remission, clinical responders, and non-responders, and pre-treatment biomarker profiles obtained at the baseline visit will be compared, as well as the immunological response to treatment. Healthy individuals and patients with mild/moderate controlled asthma are included as reference groups and will undergo the same baseline visit as patients with severe asthma. Several bio-samples, to perform multi-omic analysis, will be taken to examine biological pathways associated with response and non-response to biologics.
Detailed Description
The 3TR Consortium is the overall generator behind the 3TR-ABC study. The 3TR Consortium consists of 15 European countries and a total of 69 partners who collaborate on seven different autoimmune, inflammatory, and allergic diseases: chronic obstructive pulmonary disease, asthma, Crohn's disease, ulcerative colitis, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis. The ambition of the consortium is to accelerate precision medicine by fundamentally increasing the knowledge of molecular pathways and mechanisms related to response and non-response to therapy. To date, the 3TR Consortium is the largest immunology project funded by the Innovative Medicine Initiative (IMI). The 3TR-ABC platform study is anchored in the so-called work package 8 (WP8) within the 3TR Consortium and will contribute with knowledge about the effect of biological therapies in severe asthma: With the advent of highly targeted biological therapies for severe asthma, several important questions arise; what determines a good clinical response versus non-response? Can we induce remission of severe asthma, and improve long-term outcomes?
The 3TR-ABC study platform is a clinical trial platform and network, in which intervention-specific studies on different biologics are conducted. Via the 3TR-ABC study platform, conducting advanced translational studies in a real-life cohort of asthma patients is made possible, in collaboration with key opinion leaders and scientific experts in the field from across Europe.
The 3TR-ABC study design includes a core study visit structure, which can be expanded or amended per study to suit individual focus points.
Overall, the study design includes enrollment of bio-naïve patients with severe asthma, who have been assessed with systematic assessment, and who meet the criteria for commencing a biologic, according to national criteria in each country. Patients are then followed from the time of starting a biological treatment for three years, during which time they are followed at set time points as well as at the time of exacerbations, with sampling consisting of a core package and expanded packages, depending on the site.
By using a range of state-of-the-art and novel methods for assessing immune activation, and applying advanced bioinformatics analysis methods, The investigators expect to be able to identify immune activation patterns and response profiles that will further our understanding of disease drivers in the treatment of refractory severe asthma. Furthermore, healthy participants and patients with mild/moderate controlled asthma will be acting as controls for baseline markers thus constituting a healthy as well as mild/moderate controlled asthma reference population.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Patients with severe asthma that requires High dose ICS (corresponding to minimum 1600 micrograms Budesonide per day) + either LABA, LTRA, or LAMA OR Fixed Prednisolone treatment (OCS) minimum 50% of the time. Minimum 2 exacerbations in the last year or fixed Prednisolone treatment (OCS) minimum 50% of the time OR ACQ>1.5 AND Fulfils national criteria for specific biologic treatment.
- •Patients with mild/moderate asthma that requires Low/Medium dose of ICS/LABA +/- LTRA. ACQ < 1.
- •No exacerbations in the last year or need of Prednisolone treatment (OCS). Markers of T2 inflammation (B-eos ≥ 0.15 actual or ≥ 0.30 the last year or Sputum eos ≥ 3%, FeNO ≥ 25, allergens positivity). Not direct candidate for treatments with monoclonal antibodies.
- •Healthy volunteers that reports no respiratory diseases, No history of asthma or respiratory symptoms, normal lung function. No history of allergies. No lower or upper respiratory infections in the past 4 weeks.
Exclusion Criteria
- •Patients with severe asthma:
- •Known hypersensitivity to the active substance or any of the excipients
- •Participation in an interventional clinical trial within 3 months of visit 1 or receipt of any investigational medicinal product within 3 months or 5 half-lives. Participation in other observational studies is acceptable if in the view of the investigator it will not impact on the study outcomes.
- •Other clinically significant medical disease or uncontrolled concomitant disease that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study.
- •Patients with mild/moderate asthma:
- •Unable to understand written information due to language barriers.
- •Unable to give informed consent, i.e., patients who are incapable.
- •Show sign of symptoms of uncontrolled asthma (ACQ score higher than 1.5, OCS use, history of exacerbations within the past year).
- •Healthy volunteers:
- •Unable to understand written information due to language barriers.
- •Unable to give informed consent, i.e., patients who are incapable.
Outcomes
Primary Outcomes
No usage of oral corticosteroids in the previous 12 months
Time Frame: 1 year, 2 and 3 years
Oral corticosteroids (OCS) are a common treatment for acute asthma flare-ups to reduce inflammation and swelling in the airways. Severe asthma patients can be oral corticosteroids dependent and the reduction of the usage of oral corticosteroids will indicate a good asthma control.
Change in post- broncodilator Forced Expiratory Volume after 1 second (FEV1)
Time Frame: 1 year, 2 and 3 years
This is a validated parameter, part of regular clinical care, to assess airway obstruction using a spirometry. A dose of bronchodilator medication is administered by means of inhaler or nebulizer (such as 400mcg of salbutamol). and the spirometry is repeated after 15 minutes. An increase of the FEV1 \>10% compared to the baseline or a FEV1 ≥80% indicates good asthma control
Absense of exacerbations
Time Frame: 1 year, 2 and 3 years
Asthma exacerbations are acute or subacute episodes of progressively worsening shortness of breath, cough, wheezing, and chest tightness-or some combination of these symptoms.
Change in Asthma Control Questionnaire 5 (ACQ-5) score
Time Frame: 1 year, 2 and 3 years
This is a validated score that includes 5 questions scored from 0 to 6 with the total score being the average of the questions. The ACQ score ranges between 0 (well controlled) and 6 (extremely poorly controlled). A score of 1.5 or more indicates that a patient has inadequate asthma control.
Secondary Outcomes
- Measure airway remodeling(6 months to 1 year of benralizumab treatment)
- Change in volatile organic compounds (VOC)(1, 2, 3 years)
Investigators
Prof. dr. A.H. Maitland-van der Zee
Prof. Dr. Anke-Hilse Maitland- van der Zee
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)