Asthma; Eosinophilic Clinical Trial
— BREATHOfficial title:
BenRalizumab Effect on Airway Remodeling in Severe Eosinophilic asTHmatics
NCT number | NCT06288516 |
Other study ID # | 7484 |
Secondary ID | |
Status | Recruiting |
Phase | Phase 4 |
First received | |
Last updated | |
Start date | March 1, 2024 |
Est. completion date | June 1, 2026 |
Response to biologic therapies in severe asthma is variable, with patients being either non-responders, responders or super-responders. There is currently no explanation for this broad variation in response. It is important to examine whether these patients have distinct characteristics that could help the treating physician in making the correct diagnosis in clinical practice. Aim of this clinical study is to evaluate the efficacy of benralizumab, a humanized an anti-interleukin 5 receptor α monoclonal antibody in patients with severe eosinophilic asthma and to evaluate airway remodeling before and after benralizumab treatment. Hypothesis Identification of pathological and clinical characteristics in patients with severe eosinophilic asthma after benralizumab treatment regarding the airway remodeling, inflammatory cells, and other biomarkers on a long-term basis. Research questions Is there any improvement in airway remodeling? Are there any biomarkers to predict response to benralizumab treatment in severe eosinophilic asthmatic patients?
Status | Recruiting |
Enrollment | 45 |
Est. completion date | June 1, 2026 |
Est. primary completion date | December 31, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 85 Years |
Eligibility | Inclusion Criteria: - Written informed consent must be obtained at screening visit, before any assessment will be performed. Subjects should be able to provide informed written consent (study participation informed consent form): Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials. - Confirmed severe asthma diagnosis and treatment requirements according to American Thoracic Society(ATS)/European Respiratory Society (ERS) guidelines and Global Initiative for Asthma (GINA) 2023. - Blood eosinophils =150cells/ul at screening visit or =300cells/ul the last 12 months. - Patients with history = 1 exacerbation the previous year under the treatment of high dose of inhaled corticosteroid(ICS)+LABA±LAMA or receiving oral/systemic corticosteroids at least 3 days. For subjects on maintenance oral corticosteroids, an exacerbation requiring oral corticosteroids was defined as the use of oral/systemic corticosteroids at least double the existing dose for at least 3 days. - Meet requirements for biologic therapy with Benralizumab. Exclusion Criteria: - Asthma exacerbation, within 6 weeks prior to screening that required hospitalization or emergency room visit. - Prior use of other biologics that has potential to interfere/ affect disease progression. - Pregnant or nursing women, or women of child-bearing potential. - History of malignancy of any organ system or any other serious co-morbidities defined by the treating physician. - Patients with a history of conditions other than asthma that could result in elevated eosinophils (e.g. hypereosinophilic syndromes, Churg-Strauss Syndrome, eosinophilic esophagitis). |
Country | Name | City | State |
---|---|---|---|
Greece | Pulmonary Clinic, Aristotle University of Thessaloniki, George Papanikolaou Hospital | Thessaloniki |
Lead Sponsor | Collaborator |
---|---|
Aristotle University Of Thessaloniki | 2nd Pulmonary Clinic, Kapodistrian University of Athens, Pulmonary and Respiratory Failure Department, National and Kapodistrian University of Athens, Pulmonary Clinic, Aristotle University of Thessaloniki, Greece, Pulmonary Clinic, Democritus University of Thrace, Pulmonary Clinic, University of Ioannina, University Hospital of Crete, University Hospital of Patras |
Greece,
Bara I, Ozier A, Tunon de Lara JM, Marthan R, Berger P. Pathophysiology of bronchial smooth muscle remodelling in asthma. Eur Respir J. 2010 Nov;36(5):1174-84. doi: 10.1183/09031936.00019810. — View Citation
Berair R, Hartley R, Mistry V, Sheshadri A, Gupta S, Singapuri A, Gonem S, Marshall RP, Sousa AR, Shikotra A, Kay R, Wardlaw A, Bradding P, Siddiqui S, Castro M, Brightling CE. Associations in asthma between quantitative computed tomography and bronchial — View Citation
Kuo CW, Liao XM, Huang YC, Chang HY, Shieh CC. Bronchoscopy-guided bronchial epithelium sampling as a tool for selecting the optimal biologic treatment in a patient with severe asthma: a case report. Allergy Asthma Clin Immunol. 2019 Nov 27;15:76. doi: 10 — View Citation
Rasmussen F, Taylor DR, Flannery EM, Cowan JO, Greene JM, Herbison GP, Sears MR. Risk factors for airway remodeling in asthma manifested by a low postbronchodilator FEV1/vital capacity ratio: a longitudinal population study from childhood to adulthood. Am — View Citation
Siddiqui S, Bachert C, Bjermer L, Buchheit KM, Castro M, Qin Y, Rupani H, Sagara H, Howarth P, Taille C. Eosinophils and tissue remodeling: Relevance to airway disease. J Allergy Clin Immunol. 2023 Oct;152(4):841-857. doi: 10.1016/j.jaci.2023.06.005. Epub — View Citation
Yancey SW, Keene ON, Albers FC, Ortega H, Bates S, Bleecker ER, Pavord I. Biomarkers for severe eosinophilic asthma. J Allergy Clin Immunol. 2017 Dec;140(6):1509-1518. doi: 10.1016/j.jaci.2017.10.005. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in sub-basement membrane thickness | The identification of clinical characteristics of non-responders and super-responders. Any improvement in this parameter will be measured as change from baseline compared to measurement after 1 year of treatment. | through study completion, 52 weeks | |
Primary | Change in airway smooth muscle area | The identification of clinical characteristics of non-responders and super-responders. Any improvement in this parameter will be measured as change from baseline compared to measurement after 1 year of treatment. | through study completion, 52 weeks | |
Primary | Change in airway smooth muscle layer thickness | The identification of clinical characteristics of non-responders and super-responders. Any improvement in this parameter will be measured as change from baseline compared to measurement after 1 year of treatment. | through study completion, 52 weeks | |
Primary | Change in submucosal eosinophil number | The identification of clinical characteristics of non-responders and super-responders. Any improvement in this parameter will be measured as change from baseline compared to measurement after 1 year of treatment. | through study completion, 52 weeks | |
Primary | Change in epithelial integrity | The identification of clinical characteristics of non-responders and super-responders. Any improvement in this parameter will be measured as change from baseline compared to measurement after 1 year of treatment. | through study completion, 52 weeks | |
Primary | Change in collagen thickness | The identification of clinical characteristics of non-responders and super-responders. Any improvement in this parameter will be measured as change from baseline compared to measurement after 1 year of treatment, measured by electron microscopy. | through study completion, 52 weeks | |
Secondary | Change of cytokine and protein levels | To identify any possible biomarkers of response of non-responders versus super-responders in different biological fluids as peripheral blood and bronchial washing. The identification of clinical characteristics of non-responders and super-responders.
Change from baseline compared to measurements after 6 months and after 1 year of benralizumab treatment. |
through study completion, 52 weeks | |
Secondary | Change in exacerbation rate | Measurement of the change in exacerbation rate in each severe eosinophilic asthmatic patient under benralizumab treatment for 52 weeks of treatment. | through study completion, 52 weeks | |
Secondary | Change in blood eosinophil levels | Measurement of the change in blood eosinophil levels in each severe eosinophilic asthmatic patient under benralizumab treatment for 52 weeks of treatment. | through study completion, 52 weeks | |
Secondary | dentification of clinical characteristics of response, change in Forced Expiratory Volume (FEV1) | The identification of clinical characteristics of non-responders and super-responders. FEV1 change from baseline, before treatment initiation, compared to measurements every 3 months until 1 year of treatment. FEV1 is the maximal amount of air you can forcefully exhale in one second measured by spirometry. | through study completion, 52 weeks |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04742504 -
Interaction Between Benralizumab and Basophils in Eosinophilic Asthma
|
||
Recruiting |
NCT04565483 -
Predictive Signature of Benralizumab Response
|
Phase 4 | |
Completed |
NCT04181190 -
Effects of Anti-IL5 Biological Treatments on Blood IgE Levels in Severe Asthmatic Patients
|
||
Recruiting |
NCT05787678 -
Dupilumab Efficacy on Bronchial Inflammation, Small Airways Disfunction and Mucous Secretion
|
||
Completed |
NCT04456270 -
Asthma Control in a Dutch Primary Care Population
|
||
Not yet recruiting |
NCT05091385 -
Efficacy of Mepolizumab in Polish Patients With Severe Eosinophilic Asthma
|
||
Recruiting |
NCT05078281 -
Patients With Severe Eosinophilic Asthma Treated With Benralizumab
|
||
Recruiting |
NCT04512521 -
Functional Lung MRI for Early Treatment Response Assessment for Patients With Eosinophilic Asthma
|
||
Recruiting |
NCT05813288 -
A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma (EXHALE-3)
|
Phase 3 | |
Recruiting |
NCT04319705 -
Anti-viral Effects of Azithromycin in Patients With Asthma and COPD
|
Phase 4 | |
Active, not recruiting |
NCT03733535 -
Evaluating the Effect of Benralizumab in Severe, Poorly-controlled Eosinophilic Asthma Using Inhaled Hyperpolarized 129-Xenon MRI
|
N/A | |
Not yet recruiting |
NCT05241769 -
The Influence of Inhaled CorticoSteroids Adherence on Treatment Response to Mepolizumab in Severe Eosinophilic Asthma
|
||
Not yet recruiting |
NCT04924478 -
Evaluation of Volatile Organic Compounds in Mepolizumab Therapy
|
||
Recruiting |
NCT05763121 -
A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma.
|
Phase 3 | |
Recruiting |
NCT05748600 -
A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Eosinophilic Asthma
|
Phase 3 | |
Completed |
NCT03453021 -
Effect of Mepolizumab on Decrease of Systemic Corticosteroids in Patients With Severe Eosinophilic Asthma
|
||
Active, not recruiting |
NCT04612556 -
Efficacy of Mepolizumab in Severe Asthmatics on a Long Term (MESILICO)
|
||
Recruiting |
NCT05404763 -
Mepolizumab and Physical Activity in Severe Asthma
|
||
Completed |
NCT04710134 -
Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma
|
Phase 4 | |
Not yet recruiting |
NCT05144087 -
The Influence of Mepolizumab on Structural and Inflammatory Cells in Severe Eosinophilic Asthma
|