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

NCT07823842 | Recruiting DMC FDA Drug

• 1 other identifier: SHP2026-T2-AIR
• Study Type: observational
• Target: 538
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma; COPD (Chronic Obstructive Pulmonary Disease)

Keywords

asthma; copd; bronchiectasis; ABPA; Biologics; Type 2 inflammation

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (14)

• Time to first exacerbation;

  12 months

• Frequency of severe exacerbations

  12 months

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

  12 months

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

  12 months

• Change from baseline in COPD Assessment Test (CAT) total score at 3, 6, 9, 12 months

  12 months

Other Outcomes (3)

• Safety Objective

  12 months

• Exploratory Objectives

  12 months

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

  12 months

Study Arms (2)

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

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

Interventions

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

Also known as: Standard of Care Group

Adults with chronic airway diseases who received the standard of care

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)

Also known as: Interventional group

Adults with chronic airway diseases who have been treated with biologics

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• Subjects must meet all of the following criteria:
• \. Age ≥ 18 years; 2. Confirmed diagnosis of at least one of the following chronic airway diseases:
• 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%.
• \. Meets clinical indications for biologic therapy as judged by a respiratory or allergy specialist according to current guidelines:
• 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.
• \. 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).
• \. Able and willing to provide written informed consent and commit to at least 12 months of follow-up.

You may not qualify if:

• Subjects will be excluded if they meet any of the following criteria:
• 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;
• 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).

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200437, China

RECRUITING

Related Publications (7)

• Bhatt SP, Rabe KF, Hanania NA, Vogelmeier CF, Cole J, Bafadhel M, Christenson SA, Papi A, Singh D, Laws E, Mannent LP, Patel N, Staudinger HW, Yancopoulos GD, Mortensen ER, Akinlade B, Maloney J, Lu X, Bauer D, Bansal A, Robinson LB, Abdulai RM; BOREAS Investigators. Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts. N Engl J Med. 2023 Jul 20;389(3):205-214. doi: 10.1056/NEJMoa2303951. Epub 2023 May 21.

  PMID: 37272521 BACKGROUND

• Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, Gilmartin G, Aurivillius M, Werkstrom V, Goldman M; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29;388(10056):2115-2127. doi: 10.1016/S0140-6736(16)31324-1. Epub 2016 Sep 5.

  PMID: 27609408 BACKGROUND

• Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, Busse WW, Ford L, Sher L, FitzGerald JM, Katelaris C, Tohda Y, Zhang B, Staudinger H, Pirozzi G, Amin N, Ruddy M, Akinlade B, Khan A, Chao J, Martincova R, Graham NMH, Hamilton JD, Swanson BN, Stahl N, Yancopoulos GD, Teper A. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med. 2018 Jun 28;378(26):2486-2496. doi: 10.1056/NEJMoa1804092. Epub 2018 May 21.

  PMID: 29782217 BACKGROUND

• Sciurba FC, Criner GJ, Christenson SA, Martinez FJ, Papi A, Roche N, Bourbeau J, Korn S, Bafadhel M, Han MK, Kolterer S, Miller K, Mouneimne D, Fletcher J, Mayer B, Min J, Pavord ID; MATINEE Study Investigators. Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype. N Engl J Med. 2025 May 1;392(17):1710-1720. doi: 10.1056/NEJMoa2413181.

  PMID: 40305712 BACKGROUND

• Jia N, Jin M, Liu Y, Su N, Sun Y, Tang W, Wang G, Xie H, Xie J, Xie M, Yao X, Zhang H, Chen R, Liu C, Li J. The management of type 2 inflammatory respiratory diseases: a Chinese expert consensus [2024]. J Thorac Dis. 2025 Apr 30;17(4):1807-1831. doi: 10.21037/jtd-2024-2092. Epub 2025 Mar 25.

  PMID: 40400979 BACKGROUND

• Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, Bateman ED, Bel EH, Bleecker ER, Boulet LP, Brightling C, Chanez P, Dahlen SE, Djukanovic R, Frey U, Gaga M, Gibson P, Hamid Q, Jajour NN, Mauad T, Sorkness RL, Teague WG. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb;43(2):343-73. doi: 10.1183/09031936.00202013. Epub 2013 Dec 12.

  PMID: 24337046 BACKGROUND

• Bhatt SP, Agusti A, Bafadhel M, Christenson SA, Bon J, Donaldson GC, Sin DD, Wedzicha JA, Martinez FJ. Phenotypes, Etiotypes, and Endotypes of Exacerbations of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2023 Nov 15;208(10):1026-1041. doi: 10.1164/rccm.202209-1748SO.

  PMID: 37560988 BACKGROUND

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

1. Whole blood, DNA, and plasma 2. Sputum and sputum supernatant 3. Bronchoalveolar lavage fluid (BALF); Bronchial epithelium collected via bronchoscopy 4. Nasal swabs and nasal lavage fluid 5. Urine

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive; Bronchiectasis

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gao Yong-hua, PhD, MD

  Shanghai Pulmonary Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gao Yong-hua, PhD, MD

CONTACT

+8617321278520; gaoyonghuahust@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 8, 2026
• First Posted: September 16, 2026
• Study Start: July 30, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): May 16, 2029
• Last Updated: September 16, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)