BenRalizumab Effect on Airway Remodeling in Severe asTHma

NCT06288516 | Recruiting Phase 4 DMC

• 1 other identifier: 7484
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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?

Conditions

Asthma; Eosinophilic; Airway Remodeling

Keywords

severe asthma; airway remodeling; eosinophilic; biomarkers; bronchoscopy

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (4)

• Change of cytokine and protein levels

  through study completion, 52 weeks

• Change in exacerbation rate

  through study completion, 52 weeks

• Change in blood eosinophil levels

  through study completion, 52 weeks

• dentification of clinical characteristics of response, change in Forced Expiratory Volume (FEV1)

  through study completion, 52 weeks

Study Arms (2)

Benralizumab Arm A

EXPERIMENTAL

Benralizumab (30mg) administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks.

Drug: Benralizumab 30 mg/ml

No intervention Arm B

NO INTERVENTION

No intervention. Standard of care as treatment.

Interventions

Benralizumab 30 mg/ml DRUG

Benralizumab administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks

Also known as: biological

Benralizumab Arm A

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead
• Pulmonary Clinic, University of Ioannina: collaborator
• Pulmonary Clinic, Democritus University of Thrace: collaborator
• 2nd Pulmonary Clinic, Kapodistrian University of Athens: collaborator
• University Hospital of Crete: collaborator
• Pulmonary and Respiratory Failure Department, National and Kapodistrian University of Athens: collaborator
• University Hospital of Patras: collaborator

Study Sites (1)

Pulmonary Clinic, Aristotle University of Thessaloniki, George Papanikolaou Hospital

Thessaloniki, 57010, Greece

RECRUITING

Related Publications (6)

• 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: 10.1186/s13223-019-0378-6. eCollection 2019.

  PMID: 31798645 RESULT

• 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.

  PMID: 21037369 RESULT

• 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 J Respir Crit Care Med. 2002 Jun 1;165(11):1480-8. doi: 10.1164/rccm.2108009.

  PMID: 12045120 RESULT

• 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.

  PMID: 29221581 RESULT

• 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 2023 Jun 19.

  PMID: 37343842 RESULT

• 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 biopsy-derived airway remodelling. Eur Respir J. 2017 May 1;49(5):1601507. doi: 10.1183/13993003.01507-2016. Print 2017 May.

  PMID: 28461289 RESULT

MeSH Terms

Conditions

Pulmonary Eosinophilia; Airway Remodeling; Asthma

Interventions

benralizumab; Biological Products

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Complex Mixtures

Study Officials

• Kalliopi Domvri, Dr

  Aristotle University Of Thessaloniki

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kalliopi Domvri, Dr

CONTACT

00306940904246; kdomvrid@auth.gr

Konstantinos Porpodis, Ass Prof

CONTACT

00306944728818; kporpodis@yahoo.gr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Academic Fellow in the laboratory of Histology-Embryology

Model Details: Benralizumab (30mg) administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks

Study Record Dates

• First Submitted: February 25, 2024
• First Posted: March 1, 2024
• Study Start: March 1, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 4, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Starting 9 months after publication and ending 36 months following article publication.
• Access Criteria: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices). Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. For individual participant data meta-analysis, data will be shared. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at (Link to be provided).

Locations

GR (1)