Aggravated Airway Inflammation: Research on Biological Treatment (Mepolizumab) (AirGOs-biol)

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps; Asthma, Aspirin-Induced
• Intervention / Treatment: Drug: Placebo; Drug: Mepolizumab

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sanna Toppila-Salmi, MD PhD, PI; Phone Number: +358505431421; Email: sanna.salmi@helsinki.fi

Study Locations

• Finland
  • Helsinki, Finland, 00029
    • Recruiting
    • Helsinki University Hospital
    • Contact: Annina Lyly, MD PHD; Phone Number: +358505455051; Email: annina.lyly@hus.fi
    • Contact: Sanna K Toppila-Salmi, MD PhD; Phone Number: +358505431421; Email: sanna.salmi@helsinki.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: subcutaneous injections of placebo; Subcutaneous injections of placebo (physiological sodium chloride solution) once per month for 16 weeks. A total of 4 injections.	Drug: Placebo; Solution. Subcutaneous.
Experimental: subcutaneous injections of Mepolizumab 100 mg; Subcutaneous injections of Mepolizumab 100 mg once per month for 16 weeks. A total of 4 injections.	Drug: Mepolizumab; Solution. Subcutaneous. Mepolizumab is a biological drug, a humanized monoclonal antibody against interleukin-5.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline at Week 16 in Sinonasal Outcome Test -22 (SNOT-22) Score	SNOT-22 is a validated symptom questionnaire. The score ranges between 0 and 110. A higher score means worse outcome.	Baseline, Week 16
Change From Baseline at Week 16 in endoscopic Nasal polyp score of nasal cavity	Nasal polyp score is graded based on polyp size from 0 = no polyps to 4 = large polyps causing complete obstruction of inferior nasal cavity. The score ranges between 0 and 110. A higher score means worse outcome.The Nasal polyp score FEV1% is measured by spirometry. A higher value means better lung function = better outcome.	Baseline, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline at Week 16 in relative Forced expiatory volume in 1 second (FEV1 %) without bronchodilator.	FEV1% is measured by spirometry. It is the volume of air (in liters) exhaled in the first second during forced exhalation after maximal inspiration, in relation to the validated national reference value of subjects with similar age, gender and height.	Baseline, Week 16

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Investigators: Principal Investigator: Sanna Toppila-Salmi, MD PhD, PI, Helsinki University Hospital, Skin and Allergy Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: March 28, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Polyps; Drug-Related Side Effects and Adverse Reactions; Drug Hypersensitivity; Asthma; Inflammation; Nasal Polyps; Asthma, Aspirin-Induced
• Other Study ID Numbers: HUS/686/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No