Asthma, Aspirin-Induced, Chronic Rhinosinusitis With Nasal Polyps
Conditions
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.
Interventions
DRUGMepolizumab
Solution. Subcutaneous. Mepolizumab is a biological drug, a humanized monoclonal antibody against interleukin-5.
DRUGPlacebo
Solution. Subcutaneous.
Sponsors
Helsinki University Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 16 in Sinonasal Outcome Test -22 (SNOT-22) Score | Baseline, Week 16 | SNOT-22 is a validated symptom questionnaire. The score ranges between 0 and 110. A higher score means worse outcome. |
| Change From Baseline at Week 16 in Endoscopic Nasal Polyp Score of Nasal Cavity | Baseline, Week 16 | The nasal polyp score (NPS) is assessed bilaterally. Each nasal cavity is graded separately according to polyp size on a scale from 0 (no polyps) to 4 (large polyps causing complete obstruction of the inferior nasal cavity). The total nasal polyp score ranges from 0 to 8 points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 16 in Asthma Control Test Score | Baseline, Week 16 | The Asthma Control Test (ACT) is a validated, patient-reported questionnaire used to assess asthma control. Minimum score: 5 points. Maximum score: 25 points. 20-25 points: Well-controlled asthma. ≤15 points: Poorly controlled asthma. |
| Change in FEV1% | at 16 weeks | Percentage of observed Forced expiratory volume in 1 second (FEV1) of predicted FEV1 |
Countries
Finland
Contacts
PRINCIPAL_INVESTIGATORSanna Toppila-Salmi, MD PhD, PI
Helsinki University Hospital, Skin and Allergy Hospital
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 13.2 |
| Asthma Control Test Total points | 19.9 points STANDARD_DEVIATION 5.1 |
| Nasal polyp score | 5.5 points STANDARD_DEVIATION 1.2 |
| Race/Ethnicity, Customized Ethnicity Caucasian | 93 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 1 Participants |
| Region of Enrollment Finland | 94 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 23 Participants |
| SNOT-22 Total score | 43.5 points STANDARD_DEVIATION 16.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 47 |
| other Total, other adverse events | 8 / 48 | 4 / 47 |
| serious Total, serious adverse events | 0 / 48 | 2 / 47 |
Outcome results
None listed