Mepolizumab Effectiveness in Severe Eosinophilic Asthma and Bronchiectasis

NCT05189613 | Unknown DMC

• 1 other identifier: PoliclinicoUC
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Bronchial Asthma; Bronchiectasis

Outcome Measures

Primary Outcomes (1)

• Change from baseline of Asthma Control Test (ACT) score at Week 12 (T3), at Week 24 (T6) and at Week 52 (T12).

  Asthma Control Test (ACT) score is validated five-points scoring system, self-administered assessing the control of Asthma. Scores range from 5 points (worst asthma control) to 25 points (better asthma control). Change = Week 12 (T3) - Baseline score; Week 24 (T6) - Baseline score; Week 52 (T12) - Baseline score.

  Baseline and Week 52

Secondary Outcomes (1)

• Change from Baseline values of Spirometry values (expressed in Litre) at Week 12 (T3), at Week 24 (T6) and at Week 52 (T12).

  Baseline and Week 52

Study Arms (2)

Severe Asthma+BE

EXPERIMENTAL

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

Biological: Mepolizumab

Severe Asthma without BE

ACTIVE COMPARATOR

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

Biological: Mepolizumab

Interventions

Mepolizumab BIOLOGICAL

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

Severe Asthma without BE; Severe Asthma+BE

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female with age greater than or equal to 18 years;
• Severe eosinophilic asthma diagnosis according to GINA 2019 report
• Evidence of bronchiectasis in at least one lung lobe in the chest CT scan performed prior to mepolizumab treatment;
• Presence of daily expectoration;
• At least 3 bronchiectasis exacerbations in the year prior to mepolizumab treatment, documented through medical documentation, which required treatment with antibiotics;
• Informed consent obtained from the patient.

You may not qualify if:

• Poor adherence to severe asthma therapy
• Patients with other respiratory disease that may share common clinical manifestations of severe asthma (i.e. acute bronchopulmonary aspergillosis, vasculitis and COPD)
• 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.
• Bronchiectasis associated with cystic fibrosis;
• Traction bronchiectasis in the context of pulmonary fibrosis;
• History of lung cancer in the previous 5 years;
• History of significant hemoptysis (≥300 mL of blood) or which required embolization or blood transfusions within 6 weeks prior to mepolizumab treatment;
• Use of drugs that can influence the response to treatment such us immunosuppressant and/or biological therapies

Sponsors & Collaborators

• Policlinico Universitario, Catania: lead

Study Sites (1)

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

Catania, 95125, Italy

RECRUITING

Related Publications (11)

• 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 RESULT

• 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.

  PMID: 32994855 RESULT

• 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.

  PMID: 30453867 RESULT

• 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.

  PMID: 30461531 RESULT

• 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.

  PMID: 30881051 RESULT

• 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.

  PMID: 29548297 RESULT

• 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.

  PMID: 28544140 RESULT

• 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.

  PMID: 33329598 RESULT

• 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.

  PMID: 32347992 RESULT

• 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.

  PMID: 30049739 RESULT

• 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.

  PMID: 31277742 RESULT

MeSH Terms

Conditions

Asthma; Bronchiectasis

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Raffaele Campisi, Medicine

  Respiratory Unit Policlinico G. Rodolico-San Marco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raffaele Campisi, Medicine

CONTACT

+393392659722; raffaelemd@hotmail.it

Raffaele Campisi

CONTACT

+390953781413; raffaelemd@hotmail.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 17, 2021
• First Posted: January 12, 2022
• Study Start: September 1, 2021
• Primary Completion: June 1, 2022
• Study Completion: December 31, 2022
• Last Updated: January 12, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)