T2AIR: Real-World Efficacy and Safety of Biologics Targeting Type 2 Inflammation in Asthma and COPD (T2AIR)
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.
Visão geral do estudo
Status
Descrição detalhada
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:
- 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) 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.
Tipo de estudo
Inscrição (Estimado)
Contactos e Locais
Contato de estudo
- Nome: Gao Yong-hua, PhD, MD
- Número de telefone: +8617321278520
- E-mail: gaoyonghuahust@163.com
Locais de estudo
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Shanghai Municipality
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Shanghai, Shanghai Municipality, China, 200437
- Recrutamento
- Shanghai Pulmonary Hospital
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Contato:
- Yong-hua Gao, PhD
- Número de telefone: +8617321278520
- E-mail: gaoyonghuahust@163.com
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Contato:
- Changwei Wu, Bs.c
- Número de telefone: 021-65115006
- E-mail: gaoyonghuahust@163.com
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Investigador principal:
- Yong-hua Gao, PhD
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Método de amostragem
População do estudo
Descrição
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:
- 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%.
3. 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.
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:
- 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).
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
Coortes e Intervenções
Grupo / Coorte |
Intervenção / Tratamento |
|---|---|
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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
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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)
Outros nomes:
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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
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Patients with asthma and copd who received standard of care as recommended by relevant guidelines
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Annual rate of protocol-defined exacerbations of chronic airway disease over 12 months
Prazo: 12 months
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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.
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12 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Time to first exacerbation;
Prazo: 12 months
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Exacerbations of chronic airway diseases as defined by international guidelines: GINA 2026 (asthma) and GOLD 2026 (COPD).
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12 months
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Frequency of severe exacerbations
Prazo: 12 months
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Severe exacerbations of chronic airway diseases as defined by international guidelines: GINA 2026 (asthma), GOLD 2026 (COPD), ERS 2025 (bronchiectasis), and ERS 2024 (ABPA)
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12 months
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Change from baseline in Asthma Control Test (ACT) total score at 3, 6, 9, 12 months
Prazo: 12 months
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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.
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12 months
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Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) score at 3, 6, 9, 12 months
Prazo: 12 months
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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.
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12 months
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Change from baseline in COPD Assessment Test (CAT) total score at 3, 6, 9, 12 months
Prazo: 12 months
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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.
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12 months
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Change from baseline in modified Medical Research Council (mMRC) dyspnea scale at 3, 6, 9, 12 months
Prazo: 12 months
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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.
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12 months
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Change from baseline in Quality of Life-Bronchiectasis Respiratory Symptoms Score (QoL-B RSS) at 3, 6, 9, 12 months
Prazo: 12 months
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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.
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12 months
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Change from baseline in Bronchiectasis Impact Measure (BIM) total score at 12 months
Prazo: 12 months
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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.
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12 months
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Change from baseline in Bronchiectasis Symptom Visual Analog Scale (BS-VAS) score at 3, 6, 9, 12 months
Prazo: 12 months
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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.
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12 months
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Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at 3, 6, 9, 12 months
Prazo: 12 months
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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.
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12 months
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Lung function parameters
Prazo: 12 months
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Lung function parameters (FEV₁, FVC, and FEV₁/FVC ratio);
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12 months
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Airway inflammation and immune biomarkers
Prazo: 12 months
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Airway inflammation and immune biomarkers (fractional exhaled nitric oxide [FeNO], peripheral blood eosinophil [EOS] count, and serum IgE levels)
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12 months
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Oral corticosteroid (OCS) sparing effect in asthma patients
Prazo: 12 months
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Oral corticosteroid (OCS) sparing effect in asthma patients during treatment duration
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12 months
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Treatment persistence rate of the biologics
Prazo: 12 months
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Treatment persistence rate of the biologics during treatment duration
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12 months
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Safety Objective
Prazo: 12 months
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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.
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12 months
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Exploratory Objectives
Prazo: 12 months
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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;
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12 months
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Discriminative performance (AUROC) of a multimodal deep-learning model for predicting protocol-defined treatment response at 12 months
Prazo: 12 months
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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.
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12 months
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Gao Yong-hua, PhD, MD, Shanghai Pulmonary Hospital, Shanghai, China
Publicações e links úteis
Publicações Gerais
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Processos Patológicos
- Doença crônica
- Atributos da doença
- Doenças do sistema imunológico
- Doenças Respiratórias
- Doenças pulmonares
- Doenças brônquicas
- Doenças Pulmonares Obstrutivas
- Hipersensibilidade Respiratória
- Hipersensibilidade, Imediata
- Hipersensibilidade
- Condições Patológicas, Sinais e Sintomas
- Doença Pulmonar Obstrutiva Crônica
- Asma
- Bronquiectasia
Outros números de identificação do estudo
- SHP2026-T2-AIR
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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