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

Helsinki University Central Hospital (HUCH)

Status and phase: Completed; Phase 4

Conditions: Chronic Rhinosinusitis with Nasal Polyps; Asthma, Aspirin-Induced

Treatments: Drug: Placebo; Drug: Mepolizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT04823585

HUS/686/2020

Details and patient eligibility

About

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.

Full 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.

Enrollment: 95 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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95 participants in 2 patient groups, including a placebo group

subcutaneous injections of placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

subcutaneous injections of Mepolizumab 100 mg

Experimental group

Description:

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

Treatment:

Drug: Mepolizumab