Efficacy of Mepolizumab in Severe Asthmatics on a Long Term (MESILICO)

NCT04612556 | Active Not Recruiting DMC FDA Drug

• 1 other identifier: Study 12316
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Interleukin (IL)-5 is the main cytokine responsible for the activation of eosinophils, hence therapeutic strategies have been investigated and developed for clinical use. Biologics targeting IL-5 and its receptor (first mepolizumab and subsequently, reslizumab and benralizumab), have been recently approved and used as add-on therapy for severe eosinophilic asthma resulting in a reduction in the circulating eosinophil count, improvement in lung function and exacerbation reduction in patients with severe asthma. 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 mepolizumab, a humanized IL-5 antagonist monoclonal antibody in patients with late-onset severe eosinophilic asthma with fixed obstruction and to identify the characteristics of non-responders and super-responders under mepolizumab treatment. This study is considered as non-interventional and every procedure included is happening in a clinical routine for the diagnosis and phenotyping of the asthmatic patients. Hypothesis includes the efficacy of mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction and relation to clinical and inflammatory biomarkers. Patients will be collected from the outpatient clinics of bronchial asthma from each site included (8 in number) which cover the whole population of Greece. Overall, this is a prospective multicenter study including eight Pulmonary Clinics. Five Pulmonary University Clinics, two of National Health System and one Army General Hospital in Thessaloniki. The study will include a screening period of up to 2 weeks to assess eligibility and obtain written informed consent, a mepolizumab treatment period of 52 weeks, once every 4 weeks, including follow up visits every 3 months during treatment. The study population will consist of 45 patients with late-onset severe eosinophilic asthma and fixed obstruction receiving mepolizumab, aged 20 and above.

Conditions

Asthma; Eosinophilic; Severe Asthma; Late-Onset Asthma

Keywords

severe eosinophilic asthma, late-onset, fixed obstruction

Outcome Measures

Primary Outcomes (14)

• Change in exacerbation rate

  Mesurement of the change in exacerbation rate in each late-onset severe eosinophilic asthmatic patient with fixed obstruction under mepolizumab treatment for 52 weeks of treatment.

  through study completion, 156 weeks

• Identification 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, 156 weeks

• Identification of clinical characteristics of response, change in blood eosinophil levels.

  The identification of clinical characteristics of non-responders and super-responders. Change from baseline, before treatment initiation, compared to measurements every 3 months until 1 year of treatment.

  through study completion, 156 weeks

• Identification of clinical characteristics of response, change in FENO levels.

  The identification of clinical characteristics of non-responders and super-responders. Change from baseline, before treatment initiation, compared to measurements every 3 months until 1 year of treatment.

  through study completion, 156 weeks

• Identification of clinical characteristics of response, change in Asthma Control Questionnaire

  Identification of any improvement in patients' quality of life during mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction, from baseline, before treatment initiation, compared to every 3 months until 1 year of treatment. Questionnaire included: the Asthma Control Questionnaire (ACQ-5) to assess current asthma control. Scores range between 0 (totally controlled) and 6 (severely uncontrolled).

  through study completion, 156 weeks

• Identification of clinical characteristics of response, change in Asthma Control Test

  Identification of any improvement in patients' quality of life during mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction, from baseline, before treatment initiation, compared to every 3 months until 1 year of treatment. Questionnaire included: Asthma Control Test (ACT) to assess current asthma control. The scores range from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score \>19 indicates well-controlled asthma.

  through study completion,156 weeks

• Identification of clinical characteristics of response, change in Asthma Quality of Life Questionnaire

  Identification of any improvement in patients' quality of life during mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction, from baseline, before treatment initiation, compared to every 3 months until 1 year of treatment. Questionnaire included: the Asthma Quality of Life Questionnaire (AQLQ+12) to assess quality of life and psychological morbidity. Scores range 1-7, with higher scores indicating better quality of life.

  through study completion, 156 weeks

• Identification of clinical characteristics of response, change in Athens Insomnia Scale

  Identification of any improvement in patients' quality of life during mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction, from baseline, before treatment initiation, compared to every 3 months until 1 year of treatment. Questionnaire included: Athens Insomnia Scale (AIS) to assess sleeping quality. Total score range form 0 to 24 with higher scores indicating worst sleeping quality. AIS includes 8 questions with scores range from 0 (meaning that the item in question has not been a problem) to 3 (indicating more acute sleep difficulties).

  through study completion, 156 weeks

• Identification of clinical characteristics of response, change in Epworth Sleepiness Scale

  Identification of any improvement in patients' quality of life during mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction, from baseline, before treatment initiation, compared to every 3 months until 1 year of treatment. Questionnaire included: Epworth Sleepiness Scale (ESS) to assess sleeping quality. The total score can range from 0 to 24. Higher scores indicate increased sleepiness.

  through study completion, 156 weeks

• Identification of clinical characteristics of response, change in St. George's Respiratory Questionnaire

  Identification of any improvement in patients' quality of life during mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction, from baseline, before treatment initiation, compared to every 3 months until 1 year of treatment. Questionnaire included: St. George's Respiratory Questionnaire (SGRQ) to assess sleeping quality. Scores range from 0 to 100, with higher scores indicating more limitations.

  through study completion, 156 weeks

• Identification of clinical characteristics of response, change in WHO (Five) Well-Being Index

  Identification of any improvement in patients' quality of life during mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction, from baseline, before treatment initiation, compared to every 3 months until 1 year of treatment. Questionnaire included: WHO (Five) Well-Being Index (WHO-5) to assess sleeping quality. The total raw score ranges from 0 to 25, is multiplied by 4 to give the final score, with 0 representing the worst imaginable well-being and 100 representing the best imaginable well-being.

  through study completion, 156 weeks

• Identification of clinical characteristics of response, change in Fatigue Severity Scale

  Identification of any improvement in patients' quality of life during mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction, from baseline, before treatment initiation, compared to every 3 months until 1 year of treatment. Questionnaire included: Fatigue Severity Scale (FSS) to assess sleeping quality. FSS includes a 9-item questionnaire with questions scored on a 7 point scale with 1 meaning strongly disagree and 7 meaning strongly agree. Scores range from 9 to 63. Higher the score indicates greater fatigue severity.

  through study completion, 156 weeks

• Change in smooth muscle cell mass

  The identification of clinical characteristics of non-responders and super-responders

  through study completion, 156 weeks

• Change in Basement Membrane Thickness

  The identification of clinical characteristics of non-responders and super-responders

  through study completion, 156 weeks

Secondary Outcomes (3)

• Change in smooth muscle cell mass

  through study completion, 156 weeks

• Change of T-lympocytes percentages

  through study completion, 156 weeks

• Change of cytokine and protein levels

  through study completion, 156 weeks

Study Arms (1)

late-onset severe eosinophilic asthma and fixed obstruction

Patients with late-onset severe eosinophilic asthma and fixed obstruction will be administered Mepolizumab (100 MG), subcutaneusly every 30 days

Drug: Mepolizumab 100 MG [Nucala]

Interventions

Mepolizumab 100 MG [Nucala] DRUG

subcutaneous injection once a month

Also known as: biological/vaccine

late-onset severe eosinophilic asthma and fixed obstruction

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of 45 patients with late-onset severe eosinophilic asthma and fixed obstruction receiving mepolizumab aged 20 and above.

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 asthma diagnosis and severity and treatment requirements.
• Fixed airway obstruction (FAO) where post-bronchodilator treatment ratio of forced expiratory volume in 1 second \[FEV1\] to forced vital capacity \[FVC\] is below \< 70%.
• Confirmed optimized management skills (inhaler technique, education, adherence)
• Triggers and relevant co-morbidity have been assessed and managed Triggers such as smoking, beta-blockers, aspirin/NSAIDs, allergen exposure; Comorbidities such as rhinitis, obesity, GERD, OSA, VCD, depression/anxiety.
• Severe asthmatics with blood eosinophils ≥150cells/ul at screening visit or ≥300cells/ul the last 12 months.
• Patients with late-onset severe according to ERS/ATS guidelines eosinophilic asthma and fixed obstruction under the treatment of high dose of ICS+LABA±LAMA (late-onset asthma determined as age at diagnosis from 20 years and above)
• Patients with late-onset severe eosinophilic asthma with history ≥ 1 exacerbation the previous year under the treatment of high dose of ICS+LABA±LAMA.
• Asthma Exacerbation: Subjects with an ongoing asthma exacerbation should have their screening and treatment initiation visit delayed until the investigator considers the subject has returned to their baseline asthma status. If the 4-week screening period has elapsed then the subject should be considered a screening failure. An exacerbation is defined as worsening of asthma requiring the use of systemic corticosteroids and/or emergency department visit, or hospitalization. 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.
• Maintenance Asthma Therapy: No changes in the dose or regimen of baseline ICS and/or additional controller medication during the screening period (except for treatment of an exacerbation).
• Meet requirements for biologic therapy with mepolizumab.

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 (including but not limited to Omalizumab, Reslizumab, Dupilumab, Benralizumab etc., for asthma or any other indications) that has potential to interfere/ affect disease progression, in the previous 6 months.
• 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
• NHS Pulmonary Clinic G. Papanikolaou Hospital, Thessaloniki, Greece: collaborator
• Pulmonary Clinic of Army Hospital Thessaloniki Greece: collaborator
• Pulmonary Clinic, Democritus University of Thrace: collaborator
• Pulmonary Clinic, University of Ioannina: collaborator
• 1st Pulmonary Clinic, Kapodistrian University of Athens: collaborator
• 2nd Pulmonary Clinic, Kapodistrian University of Athens: collaborator
• NHS 7th Pulmonary Clinic, Sotiria Hospital, Athens: collaborator

Study Sites (1)

Pulmonary Clinic of Aristotle University of Thessaloniki, George Papanikolaou Hospital

Thessaloniki, Exochi, 57010, Greece

Location

Related Publications (18)

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Biospecimen

Retention: SAMPLES WITHOUT DNA

peripheral blood, bronchial washing, sputum and sputum supernatant)

MeSH Terms

Conditions

Pulmonary Eosinophilia; Asthma

Interventions

mepolizumab; Biological Products; Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Complex Mixtures

Study Officials

• Konstantinos Porpodis, Assist Prof

  Aristotle University Of Thessaloniki

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pulmonology

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: November 3, 2020
• Study Start: January 22, 2021
• Primary Completion: March 15, 2023
• Study Completion: March 15, 2025
• Last Updated: February 21, 2024

Record last verified: 2024-02

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)