Biomarkers of Response to Mepolizumab Treatment in Patients With Nasal Polyps With or Without Bronchial Asthma

NCT05708300 | Recruiting DMC FDA Drug

• 1 other identifier: Study 14879
• Study Type: observational
• Target: 57
• Locations: 1 country
• Sites: 2

Brief Summary

Mepolizumab is a biologic agent already approved for severe asthma. Recently, there is increasing evidence concerning the benefit of anti-IL5 treatments upon patients with nasal polyposis with or without severe asthma. The novelty of this project is that no biologic agent has yet been fully investigated to identify any biomarkers of response for patients with nasal polyps with or without asthma including sinonasal tissue remodeling a key element in the resultant histopathological changes of the inflammation. The investigation of airway remodeling of various locations (nose and bronchus) under mepolizumab treatment will be our primary objective on the long-term basis of 156 weeks of treatment. Endobronchial and nasal biopsies will be performed as routine care for tissue evauation and disease investigation for every patient. Besides, the united airways will provide better guidance for medical treatment of chronic rhinosinusitis (CRS) patients with nasal polyps (CRSwNP) and asthma. The initial idea is based on investigating the characteristics that could predict the effectiveness of mepolizumab on patients with nasal polyposis with or without asthma. Patients will receive 39 doses of mepolizumab for 156 weeks. An additional aim of this study is to identify characteristics of non-responders and responders to mepolizumab. Responders will be identified based on airway remodeling status, biomarkers in tissue and secretion samples and on the reduction of the need of surgery through Lund-Kennedy endoscopic score, Lund-Mackay score and patient's clinical status in the 6th, 12th and 36th month after the initiation of treatment. Regarding the unified airway system, nose and pharyngeal microbiome will be evaluated before and after 52 weeks of mepolizumab treatment in patients with nasal polyps whereas in patients with nasal polyps and asthma bronchus microbiome will also be evaluated. Lung samples will help gain information about the inflammatory profile and local microbiome of CRSwNP patients with asthma through molecular and cellular assays. The human Pharyngeal Microbiome might play a protective role in Respiratory Tract Infections and it has been reported that the microbiome provides critical signals to promote maturation of immune cells and differentiation of the tissue. Thus, we will make an effort to correlate microbiome of various locations with clinical and laboratory characteristics of responders and non-responders to mepolizumab treatment.

Conditions

Chronic Rhinosinusitis With Nasal Polyps; Asthma

Keywords

Chronic Rhinosinusitis; Nasal Polyps; Asthma

Outcome Measures

Primary Outcomes (3)

• Change in Basement Membrane Thickness

  The identification of clinical characteristics of non-responders and super-responders. Anwers whether change basement membrane thickness can predict therapeutic response of mepolizumab among patients.

  through study completion, 156 weeks

• Change in smooth muscle cell mass

  The identification of clinical characteristics of non-responders and super-responders. Anwers whether change in smooth muscle cell mass can predict therapeutic response of mepolizumab among patients.

  through study completion, 156 weeks

• Change in microbiome

  Answers whether there is a microbiome signature at baseline that can predict therapeutic response of mepolizumab among patients. The identification of clinical characteristics of non-responders and super-responders.

  through study completion, 156 weeks

Secondary Outcomes (4)

• Change of cytokine and protein levels in serum

  through study completion, 156 weeks

• Change in exacerbation rate

  through study completion, 156 weeks

• Change in requiring surgery

  through study completion, 156 weeks

• Change of cytokine and protein levels in bronchial washing

  through study completion, 156 weeks

Study Arms (2)

chronic rhinosinusitis with nasal polyps with bronchial asthma

Patients with chronic rhinosinusitis with nasal polyps with bronchial asthma will be administered Mepolizumab (100 MG), subcutaneusly every 30 days

Drug: Mepolizumab 100 MG [Nucala]

chronic rhinosinusitis with nasal polyps without bronchial asthma

Patients with chronic rhinosinusitis with nasal polyps without bronchial asthma 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: biologicals/vaccine

chronic rhinosinusitis with nasal polyps with bronchial asthma; chronic rhinosinusitis with nasal polyps without bronchial asthma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study population The study population will consist of approximately 57 patients with nasal polyposis with or without bronchial asthma receiving mepolizumab for a year aged 18 and above (no children). Clinical evaluation of patients with nasal polyposis with or without asthma will be made according to the European Position Paper on Rhinosinusitis and Nasal Polyps. Besides, standard of care for our patients apart from mepolizumab may include ICS, anti-histamine or LTRAs.

You may qualify if:

• Adult patients \> 18 years with bilateral Nasal Polyps
• Symptoms VAS scores (for nasal obstruction, hyposmia, post-nasal drip, sneezing, rhinorrhea; 0-10 for each symptom) \> 24 in spite of treatment with standard of care treatment.
• Patients with bilateral sinonasal polyps with a need for surgery as described by: Lund-Mackay score \> 4, Lund Kennedy score \> 6, a minimum total Nasal polyp score of 5 out of a maximum score of 8 at screening, ongoing symptoms for at least 12 weeks prior to screening,
• Concerning patients with asthmatics with nasal polyps: subjects must have a medical history of asthma as confirmed by asthma related symptoms and by bronchodilator response (BDR) (GINA 2022) or positive methacholine challenge according to ERS guidelines.

You may not qualify if:

• Pregnant or nursing women, or women of child-bearing potential.
• Biologic therapy (eg: Omalizumab, Mepolizumab, Reslizumab, Dupilumab) or previous treatment with Mepolizumab
• Allergen immunotherapy in the past 6 months
• Systemic corticosteroid treatment for other chronic conditions (i.e.: autoimmune disorders, tumors, etc)
• Prior/concomitant therapy: use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, or any experimental anti-inflammatory therapy) within 3 months prior to Visit 1 and during the study period.
• Evidence of active systemic immunodepression (i.e..: primary or secondary immunodeficiency)
• History of malignancy of any organ system or any other serious co-morbidities defined by the treating physician.
• Primary diagnosis of lung disease other than asthma (chronic obstructive lung disease (COPD), asthma-COPD overlap (ACO), interstitial lung disease, sarcoidosis, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, active tuberculosis, allergic bronchopulmonary aspergillosis (ABPA), current lung cancer or other blood, lymphatic or solid organ malignancy, autoimmune diseases of the skin, muscle-skeletal or gastrointestinal system needing systemic corticosteroids, immunosuppressants or biologic treatment as well as individuals with granulomatosis with polyangiitis (Wegener's granulomatosis) and eosinophilic granulomatosis polyangiitis (Churg-Strauss syndrome).
• Nasal polyps' or Asthma exacerbation, within 12 weeks prior to screening that required oral corticosteroids over 3 days or hospitalization or emergency room visit.

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead
• Department of Otorhinolaryngology, Head and Neck Surgery, George Papanikolaou Hospital: collaborator
• Department of Otorhinolaryngology, Democritus University of Thrace, Alexandroupolis: collaborator
• Department of Pulmonology, Democritus University of Thrace, Alexandroupolis: collaborator
• Respiratory Medicine Department, University of Ioannina, Faculty of Medicine: collaborator
• Department of Respiratory Medicine, National and Kapodistrian University of Athens: collaborator
• Department of Allergy and Clinical Immunology, 424 General Military Training Hospital: collaborator
• Department of Otolaryngology, Head and Neck Surgery, Sotiria General Hospital: collaborator
• Pulmonary and Respiratory Failure Department, National and Kapodistrian University of Athens: collaborator

Study Sites (2)

Pulmonary Clinic of Aristotle University of Thessaloniki, George Papanikolaou Hospital

Thessaloniki, Exochi, 57010, Greece

RECRUITING

University Pulmonary Clinic, George Papanikolaou Hospital

Thessaloniki, 57010, Greece

RECRUITING

Related Publications (7)

• Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, Toppila-Salmi S, Bernal-Sprekelsen M, Mullol J, Alobid I, Terezinha Anselmo-Lima W, Bachert C, Baroody F, von Buchwald C, Cervin A, Cohen N, Constantinidis J, De Gabory L, Desrosiers M, Diamant Z, Douglas RG, Gevaert PH, Hafner A, Harvey RJ, Joos GF, Kalogjera L, Knill A, Kocks JH, Landis BN, Limpens J, Lebeer S, Lourenco O, Meco C, Matricardi PM, O'Mahony L, Philpott CM, Ryan D, Schlosser R, Senior B, Smith TL, Teeling T, Tomazic PV, Wang DY, Wang D, Zhang L, Agius AM, Ahlstrom-Emanuelsson C, Alabri R, Albu S, Alhabash S, Aleksic A, Aloulah M, Al-Qudah M, Alsaleh S, Baban MA, Baudoin T, Balvers T, Battaglia P, Bedoya JD, Beule A, Bofares KM, Braverman I, Brozek-Madry E, Richard B, Callejas C, Carrie S, Caulley L, Chussi D, de Corso E, Coste A, El Hadi U, Elfarouk A, Eloy PH, Farrokhi S, Felisati G, Ferrari MD, Fishchuk R, Grayson W, Goncalves PM, Grdinic B, Grgic V, Hamizan AW, Heinichen JV, Husain S, Ping TI, Ivaska J, Jakimovska F, Jovancevic L, Kakande E, Kamel R, Karpischenko S, Kariyawasam HH, Kawauchi H, Kjeldsen A, Klimek L, Krzeski A, Kopacheva Barsova G, Kim SW, Lal D, Letort JJ, Lopatin A, Mahdjoubi A, Mesbahi A, Netkovski J, Nyenbue Tshipukane D, Obando-Valverde A, Okano M, Onerci M, Ong YK, Orlandi R, Otori N, Ouennoughy K, Ozkan M, Peric A, Plzak J, Prokopakis E, Prepageran N, Psaltis A, Pugin B, Raftopulos M, Rombaux P, Riechelmann H, Sahtout S, Sarafoleanu CC, Searyoh K, Rhee CS, Shi J, Shkoukani M, Shukuryan AK, Sicak M, Smyth D, Sindvongs K, Soklic Kosak T, Stjarne P, Sutikno B, Steinsvag S, Tantilipikorn P, Thanaviratananich S, Tran T, Urbancic J, Valiulius A, Vasquez de Aparicio C, Vicheva D, Virkkula PM, Vicente G, Voegels R, Wagenmann MM, Wardani RS, Welge-Lussen A, Witterick I, Wright E, Zabolotniy D, Zsolt B, Zwetsloot CP. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020 Feb 20;58(Suppl S29):1-464. doi: 10.4193/Rhin20.600.

  PMID: 32077450 RESULT

• Albers FC, Papi A, Taille C, Bratton DJ, Bradford ES, Yancey SW, Kwon N. Mepolizumab reduces exacerbations in patients with severe eosinophilic asthma, irrespective of body weight/body mass index: meta-analysis of MENSA and MUSCA. Respir Res. 2019 Jul 30;20(1):169. doi: 10.1186/s12931-019-1134-7.

  PMID: 31362741 RESULT

• Postma DS, Brightling C, Baldi S, Van den Berge M, Fabbri LM, Gagnatelli A, Papi A, Van der Molen T, Rabe KF, Siddiqui S, Singh D, Nicolini G, Kraft M; ATLANTIS study group. Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study. Lancet Respir Med. 2019 May;7(5):402-416. doi: 10.1016/S2213-2600(19)30049-9. Epub 2019 Mar 12.

  PMID: 30876830 RESULT

• Detoraki A, Tremante E, D'Amato M, Calabrese C, Casella C, Maniscalco M, Poto R, Brancaccio R, Boccia M, Martino M, Imperatore C, Spadaro G. Mepolizumab improves sino-nasal symptoms and asthma control in severe eosinophilic asthma patients with chronic rhinosinusitis and nasal polyps: a 12-month real-life study. Ther Adv Respir Dis. 2021 Jan-Dec;15:17534666211009398. doi: 10.1177/17534666211009398.

  PMID: 33910399 RESULT

• 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

• Donnell NJ, Marino MJ, Zarka MA, Lal D. Histopathological characteristics of surgical tissue from primary vs recurrent chronic rhinosinusitis with nasal polyposis patients. Laryngoscope Investig Otolaryngol. 2020 Feb 7;5(1):5-10. doi: 10.1002/lio2.358. eCollection 2020 Feb.

  PMID: 32128424 RESULT

• Diver S, Khalfaoui L, Emson C, Wenzel SE, Menzies-Gow A, Wechsler ME, Johnston J, Molfino N, Parnes JR, Megally A, Colice G, Brightling CE; CASCADE study investigators. Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021 Nov;9(11):1299-1312. doi: 10.1016/S2213-2600(21)00226-5. Epub 2021 Jul 10.

  PMID: 34256031 RESULT

Biospecimen

Retention: NONE RETAINED

blood,

MeSH Terms

Conditions

Asthma; Nasal Polyps

Interventions

mepolizumab; Biological Products; Vaccines

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Complex Mixtures

Study Officials

• Konstantinos Porpodis, Assoc Prof

  Pulmonary Clinic, Aristotle University of Thessaloniki, George Papanikolaou Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Konstantinos Porpodis, Assoc Prof

CONTACT

00306944728818; kporpodis@yahoo.gr

Kalliopi Domvri, Dr

CONTACT

00306940904246; kdomvrid@auth.gr

Study Design

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

Study Record Dates

• First Submitted: December 29, 2022
• First Posted: February 1, 2023
• Study Start: February 23, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 8, 2024

Record last verified: 2024-03

Locations

GR (2)