T2AIR: Real-World Efficacy and Safety of Biologics Targeting Type 2 Inflammation in Asthma and COPD

ConditionsAsthma COPD (Chronic Obstructive Pulmonary Disease)

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18+

SponsorShanghai Pulmonary Hospital, Shanghai, China

About this trial

This prospective, real-world observational study (T2AIR Study) evaluates the long-term efficacy and safety of six biologics targeting Type 2 inflammation - omalizumab, mepolizumab, benralizumab, dupilumab, tezepelumab, and depemokimab - in patients with chronic airway diseases, including asthma and COPD under routine clinical practice in China.

The primary objective is to determine the annualized exacerbation rate (AER) over 12 months of treatment. Secondary objectives include time to first exacerbation, frequency of severe exacerbations, improvements in symptom control and quality of life (using disease-specific questionnaires), lung function (FEV₁, FVC), airway inflammatory biomarkers (FeNO, blood eosinophils, serum IgE), oral corticosteroid (OCS) sparing effect in asthma patients, and treatment persistence.

Safety outcomes will assess the incidence, types, and severity of adverse events (AEs) and serious adverse events (SAEs). Exploratory endpoints include high-resolution CT (HRCT)-based imaging markers of airway remodeling and the development of deep learning-based multimodal predictive models integrating clinical, biomarker, and radiomics data to support personalized treatment. Additionally, blood, sputum, and urine samples will be collected for translational research to explore underlying mechanisms and predictors of biologic response.

This study aims to generate robust real-world evidence on the effectiveness and safety of Type 2-targeted biologics across the broad spectrum of chronic airway diseases in a diverse Chinese patient population.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Asthma: Diagnosed according to the 2025 GINA guidelines, with typical variable respiratory symptoms (wheeze, shortness of breath, chest tightness, or cough) and objective evidence of variable expiratory airflow limitation (positive bronchodilator reversibility test, positive bronchial provocation test, average daily PEF variability >10%, improvement in lung function after ICS treatment, or significant variability in lung function between two visits).

Chronic Obstructive Pulmonary Disease (COPD): Diagnosed according to the 2026 GOLD guidelines, with symptoms of dyspnea, chronic cough, or sputum production, and/or history of exposure to risk factors, and post-bronchodilator FEV₁/FVC < 70%.

Asthma: Poor control despite optimized high-dose ICS-LABA therapy, presence of allergic or eosinophilic inflammatory biomarkers, or severe/refractory disease requiring maintenance oral corticosteroids (OCS).

COPD: Frequent exacerbations despite triple inhaled therapy (ICS + LABA + LAMA), with blood eosinophil count (EOS) ≥ 300/μL and chronic bronchitis phenotype.

Disqualifiers

Presence of severe or uncontrolled pulmonary or systemic diseases (e.g., active malignancy, autoimmune disease) or active infectious respiratory diseases (e.g., active pulmonary tuberculosis or infectious pneumonia);

Pregnant, breastfeeding, or planning pregnancy during the study period;

Known history of hypersensitivity or allergy to any component of the planned biologic agent;

Expected life expectancy less than 12 months;

Trial population

Adult patients with chronic airway diseases (asthma, COPD) who have received biologics targeting Type 2 inflammation

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Biologics targeting Type 2 inflammation
Drug
Biologics targeting Type 2 inflammation, including Omalizumab (anti-IgE monoclonal antibody), Mepolizumab (anti-IL-5 monoclonal antibody), Benralizumab (anti-IL-5Rα monoclonal antibody), Dupilumab (anti-IL-4Rα monoclonal antibody, blocking IL-4/IL-13 signaling), Tezepelumab (anti-TSLP monoclonal antibody, effective in both T2-high and T2-low phenotypes), Depemokimab (ultra-long-acting anti-IL-5 Fc-fusion protein enabling twice-yearly dosing)
Patients with asthma and copd who received standard of care
Drug
Patients with asthma and copd who received standard of care as recommended by relevant guidelines

Treatment groups

538 Participants

are divided into 2 treatment groups

Group A: Adults with chronic airway diseases who have been treated with biologics1 intervention

Group B: Adults with chronic airway diseases who received the standard of care1 intervention

Trial outcomes

Primary outcomes

Annual rate of protocol-defined exacerbations of chronic airway disease over 12 months

Number of protocol-defined exacerbations per participant-year during the 12-month follow-up. An exacerbation is defined according to the disease-specific international criteria applicable to the participant's primary diagnosis: GINA 2026 for asthma; GOLD 2026 for COPD; ERS 2025 for bronchiectasis; and ERS 2024 for allergic bronchopulmonary aspergillosis (ABPA). Events are ascertained from participant report, medical records, and investigator assessment at scheduled and unscheduled visits.

Time frame

12 months

Secondary outcomes

Time to first exacerbation;

Exacerbations of chronic airway diseases as defined by international guidelines: GINA 2026 (asthma) and GOLD 2026 (COPD).

Time frame

12 months

Frequency of severe exacerbations

Severe exacerbations of chronic airway diseases as defined by international guidelines: GINA 2026 (asthma), GOLD 2026 (COPD), ERS 2025 (bronchiectasis), and ERS 2024 (ABPA)

Time frame

12 months

Change from baseline in Asthma Control Test (ACT) total score at 3, 6, 9, 12 months

The Asthma Control Test (ACT) is a 5-item patient-reported questionnaire assessing asthma control over the previous 4 weeks. Total score ranges from 5 to 25; higher scores indicate better asthma control. Change is calculated as 3, 6, 9, 12-month score minus baseline score.

Time frame

12 months

Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) score at 3, 6, 9, 12 months

The Asthma Control Questionnaire-6 (ACQ-6) assesses asthma symptom control. Each of 6 items is scored from 0 to 6; the total score is the mean of item scores and ranges from 0 to 6. Higher scores indicate worse asthma control. Change is 12-month score minus baseline score.

Time frame

12 months

Other outcomes

Safety Objective

To evaluate the incidence, types, and severity of adverse events (AEs) and serious adverse events (SAEs) occurring within 12 months of treatment with the different biologics in patients with chronic airway diseases.

Time frame

12 months

Exploratory Objectives

To explore novel endpoints for biologic treatment in chronic airway diseases, particularly imaging markers derived from high-resolution computed tomography (HRCT), such as airway wall thickness and functional small airway disease;

Time frame

12 months

Discriminative performance (AUROC) of a multimodal deep-learning model for predicting protocol-defined treatment response at 12 months

Area under the receiver operating characteristic curve (AUROC) for a pre-specified deep-learning model that integrates baseline clinical variables, biomarkers, and chest CT radiomics features to predict protocol-defined treatment response at 12 months. Treatment response is defined as absence of protocol-defined exacerbation during 12-month follow-up. Model input features and the response definition are specified in the statistical analysis plan. AUROC ranges from 0 to 1; higher values indicate better discrimination.

Time frame

12 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Shanghai Pulmonary Hospital, Shanghai, China

Lead sponsor

Source ClinicalTrials.gov

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