3TR Asthma Biologics Cohort (ABC) Study

NCT06126692 | Recruiting DMC

• 2 other identifiers: 831434ESR-21-21298
• Study Type: observational
• Target: 600
• Locations: 2 countries
• Sites: 2

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.

Conditions

Severe Asthma

Keywords

Remission; Monoclonal antibodies; Biologics

Outcome Measures

Primary Outcomes (4)

• Change in Asthma Control Questionnaire 5 (ACQ-5) score

  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.

  1 year, 2 and 3 years

• Change in post- broncodilator Forced Expiratory Volume after 1 second (FEV1)

  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

  1 year, 2 and 3 years

• Absense of exacerbations

  Asthma exacerbations are acute or subacute episodes of progressively worsening shortness of breath, cough, wheezing, and chest tightness-or some combination of these symptoms.

  1 year, 2 and 3 years

• No usage of oral corticosteroids in the previous 12 months

  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.

  1 year, 2 and 3 years

Secondary Outcomes (2)

• Change in volatile organic compounds (VOC)

  1, 2, 3 years

• Measure airway remodeling

  6 months to 1 year of benralizumab treatment

Other Outcomes (1)

• Variability of Fraction Exhaled Nitric Oxide (FeNO)

  3 years

Study Arms (6)

Severe asthma anti-IL5/IL-5R starters (including Benralizumab cohort)

Patients with 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.

Severe asthma anti-IL4R starters

Patients with 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.

Severe asthma anti-TLSP starters

Patients with 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.

Severe asthma anti-IgE starters

Patients with 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.

Mild/moderate controlled asthma

Low/Medium dose of ICS/LABA +/- LTRA. ACQ \< 1.5. 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 ppb, allergens positivity). Not direct candidate for treatments with monoclonal antibodies.

Healthy controls

No history of 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.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study will constitute a real-life population of patients with severe asthma, who are eligible to receive biological treatment according to relevant national criteria. The study will include all age groups. Furthermore, the study will include two control groups, a group of mild/moderate asthmatics and a group of healthy volunteers. All controls will be age-, sex-, and smoking-history-matched with the group of patients with severe asthma. The rationale behind the control groups is to compare those patients who show the best response to Anti-IgE, Anti-IL5(R), Anti-IL4/IL13, anti-TSLP treatments with those who are not candidate for a biologic therapy, both mild/moderate asthmatics and healthy individuals. In this way, the study aims to explore whether there are biomarkers indicative of a better response to monoclonal antibodies.

You may qualify if:

• 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 \< 1.5. 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Bispebjerg Hospital: collaborator
• University Hospitals, Leicester: collaborator
• Karolinska Institutet: collaborator
• University Medical Center Groningen: collaborator

Study Sites (2)

Bispebjerg Hospital

Copenhagen, 2400, Denmark

RECRUITING

Amsterdam University Medical Center

Amsterdam, North Holland, 1105AZ, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

* Blood: 75 mL * Urine: 2x 80 mL (start and end of visit + urinary pellet) * Nasal brush: 2 nasal brushes * Saliva: 3 mL * Sputum: 3x2 mL * Stool: 2x 30 mL * BAL: 2x50 mL * Brush biopsies: 4 * Mucosal biopsies: 6x50 mg, in total 300 mg * Skin biopsies: 2 punch skin biopsies

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Anke-Hilse Maitland-van der Zee, Prof.Dr.

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

• Peter Bonta, MD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

• Celeste Porsbjerg, Prof.Dr.

  Bispebjerg Hospital

  PRINCIPAL INVESTIGATOR

• Christopher E. Brightling, Prof. Dr.

  University of Leicester

  PRINCIPAL INVESTIGATOR

• Sven-Erik Dahlén, Prof. Dr.

  Karolinska Intitutet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susanne Vijverberg, Dr.

CONTACT

0031 (0)20-566 27 63; s.j.vijverberg@amsterdamumc.nl

Peter Bonta, MD

CONTACT

p.i.bonta@amsterdamumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Anke-Hilse Maitland- van der Zee

Study Record Dates

• First Submitted: August 14, 2023
• First Posted: November 13, 2023
• Study Start: January 10, 2022
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): August 1, 2033
• Last Updated: November 13, 2023

Record last verified: 2023-11

Locations

DK (1); NL (1)