Severe Chronic Rhinosinusitis with Nasal Polyposis MedDRA version: 20.1 Level: PT Classification code 10080060 Term: Chronic rhinosinusitis with nasal polyps System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants with physician-diagnosed CRSwNP for at least 12 months prior to Visit 1 that have: a. Severity consistent with need for surgery as defined by total NPS = 5 (= 2 for each nostril) at screening, as determined by the central reader b. Nasal Congestion Score (NCS) = 2 at Visit 1 c. Ongoing documented NP symptoms over > 8 weeks prior to screening such as rhinorrhea and/or reduction/loss of smell 2. SNOT-22 total score = 30 at screening (Visit 1) 3. Any standard of care for treatment of CRSwNP provided the participant is stable on that treatment for 30 days prior to Visit 1 4. Documented treatment of nasal polyposis exacerbation with SCS for at least 3 consecutive days or one IM depo-injectable dose (or contraindications/intolerance to) within the past 12 months prior to Visit 1 but not within the last 3 months prior to visit 1 and/or any history of NP surgery (or contraindications/intolerance to) Additional criteria to be checked prior to randomisation (Visit 3) 1. Confirmed central reading total NPS = 5 (= 2 for each nostril) at Visit 2 2. Bi-weekly mean NCS= 2 (baseline bi-weekly mean score collected from study Day -13 to study Day 0) 3. SNOT-22 score = 30 at randomisation (Visit 3) 4. At least 8 days of evaluable daily diary data in the 14-day period prior to randomisation (baseline bi-weekly mean score collected from study Day – 13 to study Day 0) 5. Subjects must have demonstrated a minimum 70% compliance with diary completion during the screening and run-in periods from Visit 1 to Visit 3. 6. At least 70% compliance with the participant’s background INCS as captured in the eDiary during the screening and run-in periods from Visit 1 to Visit 3. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 350 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Any clinically important comorbidities other than asthma (e.g. active lung infection, bronchiectasis, pulmonary fibrosis, cystic fibrosis, primary ciliary dyskinesia, allergic bronchopulmonary mycosis, hypereosinophilic syndromes, etc.) that could confound interpretation of clinical efficacy results. 2. Sinus surgery within 6 months of screening visit OR any sinus surgery in the past which changed the lateral wall of the nose making NPS evaluation impossible. 3. Positive COVID-19 PCR test (or COVID-19 rapid test) or COVID-19 entry screening questionnaire during the screening visit. In case of long turnaround time of the nasopharyngeal swab test results from central lab, the site has the following alternatives: - Perform COVID-19 nasopharyngeal or oropharyngeal swab test through local lab - Perform a COVID-19 rapid antigen test at the site, provided it is approved by the local health authorities. 4. Regular use of decongestants (topical or systemic) at enrolment is not allowed unless used for endoscopic procedure. 5. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine, hydroxychloroquine, systemic corticosteroids for condition or any experimental anti-inflammatory therapy) within 3 months prior to Visit 1 and during the study period. Systemic corticosteroid use is defined as treatment with a burst of systemic corticosteroids for at least 3 consecutive days or a single IM depo-injectable dose of corticosteroids (considered equivalent to a 3-day burst of systemic corticosteroids) 6. Receipt of COVID-19 vaccine (regardless of vaccine delivery platform) 28 days prior to date of IP administration at V3 (randomisation visit).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of tezepelumab on Nasal Polyp Score and Participant Reported Nasal Congestion;Secondary Objective: Key Secondary Objectives: To evaluate the effect of tezepelumab on loss of smell, nasal polyp-quality of life compared with placebo, NP surgery and/or receiving SCS for NP, sinus opacification, NPSD total symptom score (TSS), resolution/near complete resolution of nasal polyps (defined as maximum NPS of 1 in each nostril), resolution/near complete resolution of nasal polyps (defined as maximum NPS of 1 in each nostril) and NPSD TSS response, and lung function in participants with co-morbid asthma and aspirin exacerbated respiratory disease (AERD) /nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NSAID-ERD). Other Secondary Objectives: To evaluate the effect of tezepelumab on NPS, participant reported NCS, loss of smell, sinus opacification, systemic corticosteroid use, NPSD, NPIF, asthma control in participants with co-morbid asthma and AERD/NSAID-ERD, and to evaluate the PK and immunogenicity of tezepelumab.;Primary end point(s): Change from baseline in total NPS evaluated by nasal endoscopy at Week 52 and Change from baseline in bi-weekly mean NC score (NCS) evaluated as part of the Nasal Polyposis Symptom Diary (NPSD) at Week 52.;Timepoint(s) of evaluation of this end point: Baseline to Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints: At Week 52, change from baseline in bi-weekly mean loss of smell evaluated as part of the NPSD, change from baseline in SNOT-22 scores, change from baseline in Lund Mackay score (LMK) evaluated by CT, change from baseline in bi-weekly mean NPSD TSS, proportion of participants who achieve a maximum NPS of 1 in each nostril, proportion of participants who achieve a maximum NPS of 1 in each nostril and NPSD TSS response, and change from baseline in pre-BD FEV1. Time to surgery and/or SCS for NP, time to NP surgery, and time to SCS for NP up to Week 52. Other Secondary Endpoints: Through Week 52, change from baseline over time in NPS evaluated by nasal endoscopy, change from baseline over time in bi-weekly mean NCS evaluated by NPSD, change from baseline by domain of NPSD, and change from baseline in NPIF. At Week 52, proportion of participants with (i) =1 point reduction and (ii) =2 points reduction in NPS, change from baseline in loss of smell evaluated by UPSIT test, change from baseline in modified LMK score evaluated by CT, sinus severity score by quantitative CT assessment, and change from baseline in ACQ-6. Exposure of SCS over 52 Weeks. PK: Serum Concentration and Immunogenicity: Anti-drug antibody (ADA);Timepoint(s) of evaluation of this end point: Baseline to Week 52 | — |
Countries
Canada, China, Denmark, Germany, Hungary, Japan, Poland, Spain, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed