Mepolizumab Effectiveness in Severe Eosinophilic Asthma and Bronchiectasis

NCT ID: NCT05189613

Last Updated: 2022-01-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-01
• Study Completion Date: 2022-12-31

Brief Summary

Asthma is a chronic respiratory disorder characterized by bronchial inflammation and reversible bronchial obstruction. Severe asthma is an extremely heterogeneous disease, often associated with several comorbidities and risk factors. Severe uncontrolled asthma associated with bronchiectasis is an emerging phenotype. Several studies have attempted to establish an association between asthma and bronchiectasis. Mepolizumab, an Interleukin-5 (IL-5) antagonist, reduces exacerbations, eosinophils, and improves pulmonary function and asthma control. IL-5 is pivotal to eosinophils maturation and release from bone marrow, their subsequent accumulation, activation and persistence in the tissues. IL-5 therefore represents an attractive target to prevent or blunt eosinophils-mediated inflammation. The investigators hypothesize that eosinophils, stimulated by IL-5, play a crucial role in severe asthma and BE pathogenesis.

Detailed Description

Asthma is a chronic respiratory disorder in which bronchial inflammation, airway hyperresponsiveness, and reversible bronchial obstruction are operant, inciting daily symptoms and triggering unpredictable acute exacerbations. The prevalence of severe asthma varies between 5 and 10% of asthma frameworks and is estimated to account for >60% of the total costs of the disease. Severe asthma warrants Global Initiative for Asthma (GINA) Step 4 or 5 treatment, (e.g. high-dose Inhaled Corticosteroids/Long Acting Beta2-Agonists (ICS/LABA), to achieve control or remains 'uncontrolled' (entirely or in part) despite this or other appropriate therapeutic intervention. Severe asthma is an extremely heterogeneous disease, often associated with several comorbidities and risk factors, leading to divide accordingly severe asthmatic patients into homogenous groups. The result is the identification of several phenotypes of severe asthma, as those associated with obesity, smoking habit, chronic obstructive pulmonary disease (COPD), gastro-oesophageal reflux disease (GERD), chronic rhinosinusitis, nasal polyposis, infections and others. In recent years, the recognition and treatment of comorbidities is crucial because can potentially improve asthma control and outcomes. Severe uncontrolled asthma associated with bronchiectasis is an emerging phenotype. Several studies have attempted to establish an association between asthma and bronchiectasis. The prevalence of bronchiectasis (BE) is significantly higher in severe asthma (range 24-40%), then in milder disease (3%). At least one third of patients with severe asthma show the presence of BE on high resolution chest computed tomography (HRCT) scan. This phenotype has been described particularly in patients with severe, late-onset eosinophilic asthma. In order to improve the therapeutic approach to the more severe forms of asthma, biological treatments have been realized. Recently, mepolizumab, an IL-5 antagonist, was commercialized. Mepolizumab reduces exacerbations, eosinophils, and improves pulmonary function and asthma control. There is a considerable evidence that implicates eosinophils as important effector cells in the eosinophilic asthma inflammation. IL-5 is pivotal to eosinophils maturation and release from bone marrow, their subsequent accumulation, activation and persistence in the tissues. IL-5 therefore represents an attractive target to prevent or blunt eosinophils-mediated inflammation. The investigators hypothesize that eosinophils, stimulated by IL-5, play a crucial role in severe asthma and BE pathogenesis. Accumulation of eosinophils at the bronchial level causes damage by degranulation and release of toxic protein, mucus hypersecretion, elastolytic activity, mucinous cells hypertrophy and oxidative stress. Airway remodeling, due to the activity of eosinophils, is the consequence of ongoing inflammation and repair. All these tissue changes are characteristic of both asthma and bronchiectasis (BE). BE, in effect, is caused by long-term excessive inflammatory damage to the airways and in patients with asthma, eosinophils may further contribute to tissue injury. The investigators therefore hypothesize that treatment with mepolizumab, targeted against IL-5 activity, in patients with severe eosinophilic asthma associated with bronchiectasis may lead to a reduction of bronchiectasis and asthma exacerbations and lead to improve control of asthma.

Conditions

Bronchial Asthma; Bronchiectasis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Severe Asthma+BE

Patients with severe eosinophilic asthma with co-presence of Bronchiectasis (BE) in treatment with Mepolizumab

Group Type: EXPERIMENTAL

Mepolizumab

Intervention Type: BIOLOGICAL

Subcutaneous Mepolizumab (100 mcg) injection in patients with severe eosinophilic asthma

Severe Asthma without BE

Patients with severe eosinophilic asthma without Bronchiectasis (BE) in treatment with Mepolizumab

Group Type: ACTIVE_COMPARATOR

Mepolizumab

Intervention Type: BIOLOGICAL

Subcutaneous Mepolizumab (100 mcg) injection in patients with severe eosinophilic asthma

Interventions

Mepolizumab

Subcutaneous Mepolizumab (100 mcg) injection in patients with severe eosinophilic asthma

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Male and female with age greater than or equal to 18 years;

2. Severe eosinophilic asthma diagnosis according to GINA 2019 report

3. Evidence of bronchiectasis in at least one lung lobe in the chest CT scan performed prior to mepolizumab treatment;

4. Presence of daily expectoration;

5. At least 3 bronchiectasis exacerbations in the year prior to mepolizumab treatment, documented through medical documentation, which required treatment with antibiotics;

6. Informed consent obtained from the patient.

Exclusion Criteria

1. Poor adherence to severe asthma therapy

2. Patients with other respiratory disease that may share common clinical manifestations of severe asthma (i.e. acute bronchopulmonary aspergillosis, vasculitis and COPD)

3. Any medical condition or disease that was not stable during the 3 months prior to mepolizumab treatment (excluding asthma exacerbations), that the investigator believes may compromise the safety of the patient if enrolled in the study such us atrial fibrillation, acute respiratory failure, acute heart failure, myocardial infarction and acute renal failure.

4. Bronchiectasis associated with cystic fibrosis;

5. Traction bronchiectasis in the context of pulmonary fibrosis;

6. History of lung cancer in the previous 5 years;

7. History of significant hemoptysis (≥300 mL of blood) or which required embolization or blood transfusions within 6 weeks prior to mepolizumab treatment;

8. Use of drugs that can influence the response to treatment such us immunosuppressant and/or biological therapies

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Policlinico Universitario, Catania

OTHER

Sponsor Role: lead

Responsible Party

Raffaele Campisi

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Raffaele Campisi, Medicine

Role: PRINCIPAL_INVESTIGATOR

Respiratory Unit Policlinico G. Rodolico-San Marco

Locations

AOU Policlinico "G. Rodolico-Sto arrivando!n Marco"

Catania, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Raffaele Campisi, Medicine

Role: CONTACT

raffaelemd@hotmail.it

+393392659722

Raffaele Campisi

Role: CONTACT

raffaelemd@hotmail.it

+390953781413

Facility Contacts

Raffaele Campisi

Role: primary

raffaelemd@hotmail.it

+390953781413

References

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.

Reference Type: RESULT

PMID: 24337046 (View on PubMed)

Crimi C, Campisi R, Cacopardo G, Intravaia R, Nolasco S, Porto M, Pelaia C, Crimi N. Real-life effectiveness of mepolizumab in patients with severe refractory eosinophilic asthma and multiple comorbidities. World Allergy Organ J. 2020 Sep 18;13(9):100462. doi: 10.1016/j.waojou.2020.100462. eCollection 2020 Sep.

Reference Type: RESULT

PMID: 32994855 (View on PubMed)

Bardin PG, Rangaswamy J, Yo SW. Managing comorbid conditions in severe asthma. Med J Aust. 2018 Jul 16;209(S2):S11-S17. doi: 10.5694/mja18.00196.

Reference Type: RESULT

PMID: 30453867 (View on PubMed)

Perez-Miranda J, Traversi L, Polverino E. Bronchiectasis in severe asthma: a distinct phenotype? Curr Opin Pulm Med. 2019 Jan;25(1):71-78. doi: 10.1097/MCP.0000000000000542.

Reference Type: RESULT

PMID: 30461531 (View on PubMed)

Carpagnano GE, Scioscia G, Lacedonia D, Curradi G, Foschino Barbaro MP. Severe uncontrolled asthma with bronchiectasis: a pilot study of an emerging phenotype that responds to mepolizumab. J Asthma Allergy. 2019 Mar 5;12:83-90. doi: 10.2147/JAA.S196200. eCollection 2019.

Reference Type: RESULT

PMID: 30881051 (View on PubMed)

Padilla-Galo A, Olveira C, Fernandez de Rota-Garcia L, Marco-Galve I, Plata AJ, Alvarez A, Rivas-Ruiz F, Carmona-Olveira A, Cebrian-Gallardo JJ, Martinez-Garcia MA. Factors associated with bronchiectasis in patients with uncontrolled asthma; the NOPES score: a study in 398 patients. Respir Res. 2018 Mar 16;19(1):43. doi: 10.1186/s12931-018-0746-7.

Reference Type: RESULT

PMID: 29548297 (View on PubMed)

Dimakou K, Gousiou A, Toumbis M, Kaponi M, Chrysikos S, Thanos L, Triantafillidou C. Investigation of bronchiectasis in severe uncontrolled asthma. Clin Respir J. 2018 Mar;12(3):1212-1218. doi: 10.1111/crj.12653. Epub 2017 Jun 8.

Reference Type: RESULT

PMID: 28544140 (View on PubMed)

Pelaia C, Crimi C, Vatrella A, Tinello C, Terracciano R, Pelaia G. Molecular Targets for Biological Therapies of Severe Asthma. Front Immunol. 2020 Nov 30;11:603312. doi: 10.3389/fimmu.2020.603312. eCollection 2020.

Reference Type: RESULT

PMID: 33329598 (View on PubMed)

Pelaia C, Crimi C, Pelaia G, Nolasco S, Campisi R, Heffler E, Valenti G, Crimi N. Real-life evaluation of mepolizumab efficacy in patients with severe eosinophilic asthma, according to atopic trait and allergic phenotype. Clin Exp Allergy. 2020 Jul;50(7):780-788. doi: 10.1111/cea.13613. Epub 2020 May 13.

Reference Type: RESULT

PMID: 32347992 (View on PubMed)

Polverino E, Dimakou K, Hurst J, Martinez-Garcia MA, Miravitlles M, Paggiaro P, Shteinberg M, Aliberti S, Chalmers JD. The overlap between bronchiectasis and chronic airway diseases: state of the art and future directions. Eur Respir J. 2018 Sep 15;52(3):1800328. doi: 10.1183/13993003.00328-2018. Print 2018 Sep.

Reference Type: RESULT

PMID: 30049739 (View on PubMed)

Kaur R, Chupp G. Phenotypes and endotypes of adult asthma: Moving toward precision medicine. J Allergy Clin Immunol. 2019 Jul;144(1):1-12. doi: 10.1016/j.jaci.2019.05.031.

Reference Type: RESULT

PMID: 31277742 (View on PubMed)

Other Identifiers

PoliclinicoUC

Identifier Type: -

Identifier Source: org_study_id