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

September 13, 2026 updated by: Gao Yong-hua, Shanghai Pulmonary Hospital, Shanghai, China

Real-World Efficacy and Safety of Biologics Targeting Type 2 Inflammation Across the Spectrum of Chronic Airway Diseases - A Prospective Observational Study in Asthma and COPD

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Chronic airway diseases, encompassing asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous disorders characterized by chronic airway inflammation, persistent airflow limitation, and/or airway hyperresponsiveness. These conditions commonly present with chronic cough, sputum production, and dyspnea. Acute exacerbations can be life-threatening and represent a leading global cause of disability and premature mortality among chronic non-communicable diseases.

Although inhaled corticosteroids (ICS) combined with long-acting bronchodilators (LABA/LAMA) form the mainstay of treatment, a substantial proportion of patients - approximately 5-10% with asthma and selected COPD patients experience severe or refractory disease. These patients suffer from recurrent exacerbations, progressive lung function decline, impaired quality of life, and serious complications associated with long-term oral corticosteroid (OCS) use, including osteoporosis and increased infection risk.

Type 2 (T2-high) inflammation, driven by eosinophil activation and the IL-4/IL-5/IL-13 signaling pathways, plays a central role in the pathogenesis of most severe asthma cases and a significant subset of COPD patients. In recent years, biologics targeting key mediators of Type 2 inflammation - including IgE, IL-5/IL-5Rα, IL-4Rα, and thymic stromal lymphopoietin (TSLP) - have emerged as precision therapeutic options for patients inadequately controlled on standard therapy.

The six biologics evaluated in this study are:

  1. Omalizumab (anti-IgE monoclonal antibody)
  2. Mepolizumab (anti-IL-5 monoclonal antibody)
  3. Benralizumab (anti-IL-5Rα monoclonal antibody)
  4. Dupilumab (anti-IL-4Rα monoclonal antibody, blocking IL-4/IL-13 signaling)
  5. Tezepelumab (anti-TSLP monoclonal antibody, effective in both T2-high and T2-low phenotypes)
  6. Depemokimab (ultra-long-acting anti-IL-5 Fc-fusion protein enabling twice-yearly dosing) Current international guidelines (GINA 2026 and GOLD 2026) recommend these Type 2-targeted biologics as add-on therapy for moderate-to-severe patients with poor control despite optimized standard care, with selection often guided by biomarkers such as blood eosinophils (EOS) and fractional exhaled nitric oxide (FeNO). While these agents have demonstrated efficacy in randomized controlled trials (RCTs) for severe asthma and eosinophilic COPD, robust real-world evidence remains limited, long-term use, diverse phenotypes, elderly patients, and those with multiple comorbidities. Moreover, data specific to Chinese populations are scarce. This prospective real-world observational study aims to address these evidence gaps.

Study Type

Observational

Enrollment (Estimated)

538

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200437
        • Recruiting
        • Shanghai Pulmonary Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yong-hua Gao, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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

Description

Inclusion Criteria

Subjects must meet all of the following criteria:

1. Age ≥ 18 years; 2. Confirmed diagnosis of at least one of the following chronic airway diseases:

  1. 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).
  2. 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%.

3. Meets clinical indications for biologic therapy as judged by a respiratory or allergy specialist according to current guidelines:

  1. 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).
  2. COPD: Frequent exacerbations despite triple inhaled therapy (ICS + LABA + LAMA), with blood eosinophil count (EOS) ≥ 300/μL and chronic bronchitis phenotype.

4. The treating respiratory or allergy specialist has decided to initiate or switch to one of the following approved biologics targeting Type 2 inflammation, based on 2025 GINA and 2026 GOLD guidelines: omalizumab, mepolizumab, benralizumab, dupilumab, tezepelumab, or depemokimab (tezepelumab may be used in both Type 2 and non-Type 2 inflammation).

5. Able and willing to provide written informed consent and commit to at least 12 months of follow-up.

Exclusion Criteria

Subjects will be excluded if they meet any of the following criteria:

  1. 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);
  2. Pregnant, breastfeeding, or planning pregnancy during the study period;
  3. Known history of hypersensitivity or allergy to any component of the planned biologic agent;
  4. Expected life expectancy less than 12 months;
  5. Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation (e.g., poor compliance or inability to complete follow-up).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Adults with chronic airway diseases who have been treated with biologics
Patients with chronic airway diseases who have been treated with biologics targeting Type 2 inflammation and met the study's inclusion criteria
Drug: Biologics targeting Type 2 inflammation
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)
Other Names:
  • Interventional group
Adults with chronic airway diseases who received the standard of care
Adults with chronic airway diseases who received the standard of care as recommended by relevant guidelines
Drug: Patients with asthma and copd who received standard of care
Patients with asthma and copd who received standard of care as recommended by relevant guidelines
Other Names:
  • Standard of Care Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annual rate of protocol-defined exacerbations of chronic airway disease over 12 months
Time Frame: 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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first exacerbation;
Time Frame: 12 months
Exacerbations of chronic airway diseases as defined by international guidelines: GINA 2026 (asthma) and GOLD 2026 (COPD).
12 months
Frequency of severe exacerbations
Time Frame: 12 months
Severe exacerbations of chronic airway diseases as defined by international guidelines: GINA 2026 (asthma), GOLD 2026 (COPD), ERS 2025 (bronchiectasis), and ERS 2024 (ABPA)
12 months
Change from baseline in Asthma Control Test (ACT) total score at 3, 6, 9, 12 months
Time Frame: 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.
12 months
Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) score at 3, 6, 9, 12 months
Time Frame: 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.
12 months
Change from baseline in COPD Assessment Test (CAT) total score at 3, 6, 9, 12 months
Time Frame: 12 months
The COPD Assessment Test (CAT) is an 8-item questionnaire. Total score ranges from 0 to 40; higher scores indicate worse health status. Change is 3, 6, 9, 12-month score minus baseline score.
12 months
Change from baseline in modified Medical Research Council (mMRC) dyspnea scale at 3, 6, 9, 12 months
Time Frame: 12 months
The modified Medical Research Council (mMRC) dyspnea scale ranges from 0 to 4; higher scores indicate more severe dyspnea. Change is 3, 6, 9, 12-month grade minus baseline grade.
12 months
Change from baseline in Quality of Life-Bronchiectasis Respiratory Symptoms Score (QoL-B RSS) at 3, 6, 9, 12 months
Time Frame: 12 months
The Quality of Life-Bronchiectasis (QoL-B) Respiratory Symptoms Score is a domain of the QoL-B questionnaire. Domain scores range from 0 to 100; higher scores indicate fewer respiratory symptoms / better health status. Change is 3, 6, 9, 12-month score minus baseline score. This instrument is only measured for patients with bronchiectasis.
12 months
Change from baseline in Bronchiectasis Impact Measure (BIM) total score at 12 months
Time Frame: 12 months
The Bronchiectasis Impact Measure (BIM) is a patient-reported instrument assessing the impact of bronchiectasis. Total score ranges from 0 to 100; higher scores indicate greater disease impact (worse outcome). Change is 3, 6, 9, 12-month score minus baseline score. This instrument is only measured for patients with bronchiectasis.
12 months
Change from baseline in Bronchiectasis Symptom Visual Analog Scale (BS-VAS) score at 3, 6, 9, 12 months
Time Frame: 12 months
The Bronchiectasis Symptom Visual Analog Scale (BS-VAS) measures overall bronchiectasis symptom burden on a 10-mm visual analog scale ranging from 0 to 10. Higher scores indicate worse symptoms. Change is 3, 6, 9, 12-month score minus baseline score. This instrument is only measured for patients with bronchiectasis.
12 months
Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at 3, 6, 9, 12 months
Time Frame: 12 months
The St. George's Respiratory Questionnaire (SGRQ) total score ranges from 0 to 100; higher scores indicate worse health-related quality of life. Administered to participants with asthma or COPD, and to participants with ABPA who have comorbid asthma. Change is 3, 6, 9, 12-month score minus baseline score.
12 months
Lung function parameters
Time Frame: 12 months
Lung function parameters (FEV₁, FVC, and FEV₁/FVC ratio);
12 months
Airway inflammation and immune biomarkers
Time Frame: 12 months
Airway inflammation and immune biomarkers (fractional exhaled nitric oxide [FeNO], peripheral blood eosinophil [EOS] count, and serum IgE levels)
12 months
Oral corticosteroid (OCS) sparing effect in asthma patients
Time Frame: 12 months
Oral corticosteroid (OCS) sparing effect in asthma patients during treatment duration
12 months
Treatment persistence rate of the biologics
Time Frame: 12 months
Treatment persistence rate of the biologics during treatment duration
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Objective
Time Frame: 12 months
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.
12 months
Exploratory Objectives
Time Frame: 12 months
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;
12 months
Discriminative performance (AUROC) of a multimodal deep-learning model for predicting protocol-defined treatment response at 12 months
Time Frame: 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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Pulmonary Hospital, Shanghai, China

Investigators

  • Principal Investigator: Gao Yong-hua, PhD, MD, Shanghai Pulmonary Hospital, Shanghai, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2026

Primary Completion (Estimated)

March 31, 2029

Study Completion (Estimated)

May 16, 2029

Study Registration Dates

First Submitted

September 8, 2026

First Submitted That Met QC Criteria

September 13, 2026

First Posted (Actual)

September 16, 2026

Study Record Updates

Last Update Posted (Actual)

September 16, 2026

Last Update Submitted That Met QC Criteria

September 13, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHP2026-T2-AIR

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe