Aggravated Airway Inflammation: Research on Biological Treatment (Mepolizumab)

NCT ID: NCT04823585

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-12
• Study Completion Date: 2025-01-16

Brief Summary

Primary objective:

to investigate the efficacy of Mepolizumab 100 milligram (mg) every month compared to placebo in reducing validated Sinonasal Outcome Test -22 score and on reducing endoscopic Nasal Polyp Score. The participants have a triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma and non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The investigators will evaluate whether mepolizumab reduces the need for increased drug dosage (topical corticosteroid or bronchodilator dosage) and improves lung and nasal function more effectively than placebo.

This first visit ensures the inclusion and exclusion criteria of the subject. If necessary, NERD will be verified by an ASA challenge test at a second additional visit. Participants have also 6 visits, on four of which subcutaneous injection of the study product is administered. During visits, a clinical examination, airway function tests, and nasal, blood, urine, and stool samples are also taken to elucidate predictive biomarkers of severely symptomatic NERD patients.

Detailed Description

Primary objective:

to investigate the efficacy of Mepolizumab 100 milligram (mg) every month compared to placebo in reducing validated Sinonasal Outcome Test -22 score and on reducing endoscopic Nasal Polyp Score. The participants have a triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma and non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The investigators will evaluate whether mepolizumab reduces the need for increased drug dosage (topical corticosteroid or bronchodilator dosage) and improves lung and nasal function more effectively than placebo.

This first visit ensures the inclusion and exclusion criteria of the subject. If necessary, NERD will be verified by an ASA challenge test at a second additional visit. Participants have also 6 visits, on four of which subcutaneous injection of the study product is administered. During visits, a clinical examination, airway function tests, and nasal, blood, urine, and stool samples are also taken to elucidate predictive biomarkers of severely symptomatic NERD patients.

Conditions

Asthma, Aspirin-Induced; Chronic Rhinosinusitis with Nasal Polyps

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

subcutaneous injections of placebo

Subcutaneous injections of placebo (physiological sodium chloride solution) once per month for 16 weeks. A total of 4 injections.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Solution. Subcutaneous.

subcutaneous injections of Mepolizumab 100 mg

Subcutaneous injections of Mepolizumab 100 mg once per month for 16 weeks. A total of 4 injections.

Group Type: EXPERIMENTAL

Mepolizumab

Intervention Type: DRUG

Solution. Subcutaneous. Mepolizumab is a biological drug, a humanized monoclonal antibody against interleukin-5.

Interventions

Mepolizumab

Solution. Subcutaneous. Mepolizumab is a biological drug, a humanized monoclonal antibody against interleukin-5.

Intervention Type: DRUG

Placebo

Solution. Subcutaneous.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ≥18 years of age
• Exacerbation of respiratory symptoms by acetylsalicylic acid (ASA) or another NSAID. (NERD will be verified by another visit if necessary).
• chronic rhinosinusitis with bilateral polyps. Endoscopic bilateral nasal polyp score of at least 5 (out of 8), with a minimum score of 2 in each nasal cavity
• Lund Mackay score ≥12 (maximum 24) of sinus computed tomography (CT) or cone beam (CBCT) scans. The new sinus CT/CBCT scans are needed if the previous sinus CT/CBCT scans have been performed over 36 months before recruitment visit or if there is a suspicion of complication of CRS (f.ex. mucocele, invasive fungal rhinosinusitis). Pregnant and breast-feeding subject will be excluded. Females of Reproductive Potential (FRPs) who are not pregnant or breast-feeding may be enrolled. FRPs need to perform pregnancy test prior to the CT/CBCT scans. If subject is already on contraception prior to the study this should be continued. The data of previous sinus CT/CBCT scans will be used if previous sinus CT/CBCT scans have been performed ≤36 months prior to recruitment visit. The clinical information of sinus CT/CBCT scans is critical to enrolling appropriate subjects for the research and cannot readily be obtained another way. The radiation dose of sinus CT/CBCT scans is less than 0.1 mSv, which corresponds to less than 10 days of natural background radiation in Finland. This dose has not been shown to increase the cancer risk.
• ≥1 previous CRS-surgery. Note that the last CRS-surgery must have been performed at least 6 months before 1st visit
• SNOT-22 ≥25
• At least one other symptom, such as partial loss of smell (hyposmia), nasal obstruction, total loss of smell (anosmia), or anterior or posterior rhinorrhea
• patient should have a history of at least one exacerbation during the past two years e.g. at least one criterion must be fulfilled of the following list during the past two years ≥1 oral corticosteroids; ≥3 antibiotic courses; ≥1 CRS-operation; ≥ 1 asthma hospitalization. In patients with contraindications of previously listed treatment or continuous oral steroids, additional criteria are not required.
• Asthma diagnosis (patient has the National Social Insurance Institution´s reimbursement right for asthma medication)
• Peripheral blood eosinophils (PBEos) >300 cells/ul at visit 1 OR (PBEos >150 cells/ul at visit 1 AND a history of PBEos >300 cells/ul during the past 12 months). A history of Nasal polyp tissue eosinophilia (NPeos) ≥30% during the past 12 months is a supportive criterion.

Exclusion Criteria

• Age <18 years
• Age > 70 years
• CRS-surgery < 6 months before 1st visit
• pregnancy/ breastfeeding. FRPs need to perform pregnancy test prior to the CT/CBCT scans. If subject is already on contraception prior to the study this should be continued.
• complication of CRS (f.ex. mucocele, invasive fungal rhinosinusitis). Take sinus CT/CBCT scans, if needed!
• acute rhinosinusitis/respiratory infection
• severe disease related to airways/ immunology: cystic fibrosis, primary ciliary dyskinesia (PCD), sarcoidosis, immunosuppression, diagnosed Specific antibody deficiency (SAD), CVI, HIV, fungal rhinosinusitis; Young syndrome; Kartagener syndrome;
• other severe disease such as active cancer
• Received biologic therapy/systemic immunosuppressant/ASA desensitization therapy/experimental monoclonal antibody treatment to treat inflammatory or autoimmune disease within 2 months of study entry or 5 half-lives, whichever is longer. The patient is allowed to use ASA dose <100 mg/day due to cardiovascular reasons after ASA desensitization.
• current immunotherapy
• communication problems (f.ge. neurological/psychiatric disease, language skills)
• unlikely to comply
• ASA-challenge negative.
• History of hypersensitivity to mepolizumab or excipients in the formulation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helsinki University Central Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sanna Salmi

Professor MD PhD Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sanna Toppila-Salmi, MD PhD, PI

Role: PRINCIPAL_INVESTIGATOR

Helsinki University Hospital, Skin and Allergy Hospital

Locations

Helsinki University Hospital

Helsinki, , Finland

Countries

Finland

References

Lyly A, Sahlman J, Pajala K, Salminen M, Sillanpaa S, Numminen J, Hanif T, Laulajainen-Hongisto A, Makela M, Kauppi P, Kangasniemi I, Lilja M, Hammaren-Malmi S, Virkkula P, Toppila-Salmi S. Study protocol for a randomized double-blinded placebo-controlled trial on mepolizumab for patients with chronic rhinosinusitis with nasal polyps, NSAID exacerbated respiratory disease and asthma. Front Allergy. 2025 Mar 21;6:1568081. doi: 10.3389/falgy.2025.1568081. eCollection 2025.

Reference Type: DERIVED

PMID: 40191526 (View on PubMed)

Other Identifiers

HUS/686/2020

Identifier Type: -

Identifier Source: org_study_id