Beyond EOsinophils: proteoMICS to Identify Potential Biomarker of Organ Damage and Response to MEPOLIZUMAB in EGPA

NCT07343661 | Enrolling By Invitation Phase 4

• 2 other identifiers: 14918-219771GSK IIS Study 14918-219771
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Aim of the study is to identify potential biomarkers, through a proteomic approach, which could be used to evaluate organ damage and predict the response to mepolizumab in a cohort of patients affected by EGPA. Proteomic analyses will be performed using a proteomic platform, based on a nano-HPLC- couplet to an high resolution ESI-MS device, on three types of biological matrices: blood, saliva and sputum samples in both EGPA and severe asthmatic patients (as controls) at baseline and at different time points after starting treatment with mepolizumab, an anti-IL-5 drug, in order to cluster patients and to analyze the effect of the therapy during treatment, assessing the disease progression on three key aspects: lung function and symptoms control, vasculitis and neuropathy. Plasma analysis will provide an overview of quantitative/qualitative proteomic variations at systemic level after drug administration; however, a less invasive procedure is often sufficient and would improve trial recruitment. On this regard, saliva is a biological fluid well suitable to be used in proteomic investigations for suggestion of potential disease biomarkers and includes various potential advantages compared with blood sample collection such as lower overall cost, lower infection risk, increased patient convenience, acceptability, compliance and uptake. Moreover, the protein composition of the human saliva includes both specific proteins of the oral cavity and proteins common to other tissues and bodily fluids, so saliva prognostic and diagnostic role is particularly interesting. Consequently, the plan is to compare the proteomic results of the non-invasive saliva testing to that of blood examination. These data may be a further step to untangle the mechanisms of the disease and to characterize treatment's response, in the contest of a phenotype/endotype asthma management.

Conditions

EGPA - Eosinophilic Granulomatosis With Polyangiitis; Severe Asthma; Eosinophilic Asthma

Keywords

EGPA; severe asthma; eosinophilic asthma

Outcome Measures

Primary Outcomes (1)

• Saliva, sputum, and plasma proteomic profile of EGPA patients

  Obtain a proteomic profile of EGPA patients and severe asthmatic patients from blood, saliva and sputum. Analyse the samples after starting anti IL - 5 treatment ( mepolizumab ) and evaluate the possible disease modifying effect of the mepoliumab on vas

  From the data to the enrollment until the end of the study, up to 52 weeks.

Secondary Outcomes (1)

• If it is possible to predict the response to treatment by analyzing the proteomic profile of the patients.

  From date of randomization until the date of first documented progression, assessed up to 24 months

Study Arms (3)

EGPA with predominant ENT/asthmatic phenotype

EXPERIMENTAL

Mepolizumab treatment

Drug: Mepolizumab 300 mg

EGPA with vasculitic phenotype

EXPERIMENTAL

immunosuppressive drugs (CYC, AZA, MTX) and/or Mepolizumab

Drug: Mepolizumab 300 mg

severe eosinophilic asthma

ACTIVE COMPARATOR

before and after Mepolizumab treatment

Drug: Mepolizumab 100 MG Injection [Nucala]

Interventions

Mepolizumab 100 MG Injection [Nucala] DRUG

collect blood, salivary and sputum samples in both EGPA and severe asthmatic patients (as controls) at baseline and at different timepoints after starting treatment with mepolizumab, an anti-IL-5 drug, in order to cluster patients and to analyse the effect of the therapy during treatment and assess the disease progression on three key aspects of the disease: lung function and symptoms control, vasculitis and neuropathy.

severe eosinophilic asthma

Mepolizumab 300 mg DRUG

collect blood, salivary and sputum samples in both EGPA and severe asthmatic patients (as controls) at baseline and at different timepoints after starting treatment with mepolizumab, an anti-IL-5 drug, in order to cluster patients and to analyse the effect of the therapy during treatment and assess the disease progression on three key aspects of the disease: lung function and symptoms control, vasculitis and neuropathy.

EGPA with predominant ENT/asthmatic phenotype; EGPA with vasculitic phenotype

Eligibility Criteria

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

You may qualify if:

• Informed Consent: Prior to start any study related activities, participants must be able and willing to provide written informed consent;
• Participants must have a current clinical diagnosis of asthma or EGPA;
• Physician decision to initiate treatment with mepolizumab.
• Patient has to be in treatment with medium-high dose ICS plus an additional controller in the least 6 months before screening and, if on OCS therapy, a stable dosage of prednisone (or equivalent dose of other steroids) in the 4 weeks before screening will be allowed. The above-indicated treatment has to be maintained by the patient all along the study.
• Adults aged 18 years or over.

You may not qualify if:

• Asthmatic patients receiving other biological treatment
• Participation in an interventional clinical trial in which the treatment regimen and/or monitoring is dictated by a protocol during the previous 12 months.
• Pregnant and breastfeeding woman

Sponsors & Collaborators

• Azienda Ospedaliero Universitaria di Cagliari: lead

Study Sites (1)

Policlinico Duilio Casula AOU Cagliari

Cagliari, Cagliari, Italy

Location

Related Publications (6)

• Steinfeld J, Bradford ES, Brown J, Mallett S, Yancey SW, Akuthota P, Cid MC, Gleich GJ, Jayne D, Khoury P, Langford CA, Merkel PA, Moosig F, Specks U, Weller PF, Wechsler ME. Evaluation of clinical benefit from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis. J Allergy Clin Immunol. 2019 Jun;143(6):2170-2177. doi: 10.1016/j.jaci.2018.11.041. Epub 2018 Dec 19.

  PMID: 30578883 BACKGROUND

• Wechsler ME, Akuthota P, Jayne D, Khoury P, Klion A, Langford CA, Merkel PA, Moosig F, Specks U, Cid MC, Luqmani R, Brown J, Mallett S, Philipson R, Yancey SW, Steinfeld J, Weller PF, Gleich GJ; EGPA Mepolizumab Study Team. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017 May 18;376(20):1921-1932. doi: 10.1056/NEJMoa1702079.

  PMID: 28514601 BACKGROUND

• Kahn JE, Grandpeix-Guyodo C, Marroun I, Catherinot E, Mellot F, Roufosse F, Bletry O. Sustained response to mepolizumab in refractory Churg-Strauss syndrome. J Allergy Clin Immunol. 2010 Jan;125(1):267-70. doi: 10.1016/j.jaci.2009.10.014. No abstract available.

  PMID: 20109753 BACKGROUND

• Puechal X, Pagnoux C, Baron G, Lifermann F, Geffray L, Quemeneur T, Saraux JL, Wislez M, Cottin V, Ruivard M, Limal N, Aouba A, Bonnotte B, Neel A, Agard C, Cohen P, Terrier B, Le Jeunne C, Mouthon L, Ravaud P, Guillevin L; French Vasculitis Study Group investigators. Non-severe eosinophilic granulomatosis with polyangiitis: long-term outcomes after remission-induction trial. Rheumatology (Oxford). 2019 Dec 1;58(12):2107-2116. doi: 10.1093/rheumatology/kez139.

  PMID: 31056661 BACKGROUND

• Samson M, Puechal X, Devilliers H, Ribi C, Cohen P, Stern M, Pagnoux C, Mouthon L, Guillevin L; French Vasculitis Study Group. Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) enrolled in two prospective trials. J Autoimmun. 2013 Jun;43:60-9. doi: 10.1016/j.jaut.2013.03.003. Epub 2013 Apr 13.

  PMID: 23590801 BACKGROUND

• Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-11. doi: 10.1002/art.37715. No abstract available.

  PMID: 23045170 BACKGROUND

MeSH Terms

Conditions

Churg-Strauss Syndrome; Asthma; Pulmonary Eosinophilia

Interventions

mepolizumab; Injections

Condition Hierarchy (Ancestors)

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• STEFANO DEL GIACCO, MD

  AZIENDA OSPEDALIERA UNIVERSITARIA CAGLIARI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: sub investigator

Model Details: According to the patients' groups evaluated in other publications with a robust statistical method and sample size calculation performed by the team, a sample of 90 patients can be considered sufficient to allow the realization of the study. The investigators plan to enroll 90 patients followed in Allergy and Clinical Immunology Centers divided into three groups: * 30 patients with EGPA with predominant ENT/asthmatic phenotype (longitudinal sampling before and after Mepolizumab treatment) * 30 patients with EGPA with vasculitic phenotype before and after immunosuppressive drugs (CYC, AZA, MTX) and/or Mepolizumab. * 30 patients with a diagnosis of severe eosinophilic asthma (longitudinal sampling before and after Mepolizumab treatment)

Study Record Dates

• First Submitted: September 25, 2025
• First Posted: January 15, 2026
• Study Start: October 17, 2025
• Primary Completion (Estimated): October 17, 2026
• Study Completion (Estimated): September 30, 2028
• Last Updated: January 15, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)