A Multicentre, Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Tezepelumab in Participants with Severe Chronic Rhinosinusitis with Nasal Polyposis
This is a multicentre, randomised, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of tezepelumab in adults with severe, chronic rhinosinusitis with nasal polyposis. Approximately 400 subjects will be randomized globally. Participants will receive tezepelumab, or placebo, administered via subcutaneous injection using the accessorized pre-filled syringe (APFS) every 4 weeks, over a 52-week treatment period. The study also includes a post-treatment follow-up period of 12-24 weeks for participants who complete the 52-week treatment period. All participants will have background mometasone furoate nasal spray or equivalent intranasal corticosteroid at a stable dose from Visit 1 and throughout the screening and study period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
416
Tezepelumab subcutaneous injection
Placebo subcutaneous injection
Background MFNS or equivalent INCS at stable dose
Change From Baseline in Total Nasal Polyp Score at Week 52
The total nasal polyp score (NPS) is the sum of the right and left nostril scores (maximum of 8), as evaluated by nasal endoscopy. Higher scores indicate greater symptom severity. The left and right score will be based on a central read with a scale from 0 to 4. Each nasal endoscopy is evaluated by two independent physician reviewers.
Time frame: Baseline to Week 52
Change From Baseline in Bi-weekly Mean Nasal Congestion Score (NCS) at Week 52
The NCS is captured by one item in the NPSD (nasal polyps symptom diary) asking participants to rate the severity of their worst NC over the past 24 hours using the following response options: 0 - None; 1 - Mild; 2 - Moderate; 3 - Severe. Baseline will be the mean of daily responses from Day -13 to Day 0. Bi-weekly (14-day) mean NCS will be calculated if at least 8 days in each 14-day period has evaluable data; otherwise the bi-weekly mean is set to missing.
Time frame: Baseline to Week 52
Change From Baseline in Bi-weekly Mean Loss of Smell at Week 52
Participant reported sense of smell will be evaluated as part of the NPSD. Loss of smell is captured by the DSS item (difficulty with sense of smell) in the NPSD asking participants to rate the severity of their worst difficulty with sense of smell over the past 24 hours using the following response options: 0 - None; 1 - Mild; 2 - Moderate; 3 - Severe. Baseline will be the mean of daily responses to the from Day -13 to Day 0. Bi-weekly (14-day) mean loss of smell will be calculated if at least 8 days in each 14-day period has evaluable data; otherwise the bi-weekly mean is set to missing.
Time frame: Baseline to Week 52
Change From Baseline in SinoNasal Outcome Test 22 (SNOT-22) at Week 52
SinoNasal Outcome Test 22 scores are participant-reported and assess physical problems, functional limitations and emotional consequences of SinoNasal conditions. Patient-reported symptom severity and symptom impact over the past 2 weeks are captured via a 6-point scale (0-No Problem to 5-Problem as bad as it can be). The total score is the sum of item scores and has a range from 0 to 110 (higher scores indicate poorer outcomes).
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Research Site
Birmingham, Alabama, United States
Research Site
Bakersfield, California, United States
Research Site
Newport Beach, California, United States
Research Site
Roseville, California, United States
Research Site
Walnut Creek, California, United States
Research Site
Colorado Springs, Colorado, United States
Research Site
Denver, Colorado, United States
Research Site
Boca Raton, Florida, United States
Research Site
Chicago, Illinois, United States
Research Site
Baltimore, Maryland, United States
...and 102 more locations
Time frame: Baseline to Week 52
Change From Baseline in Lund Mackay Score Evaluated by CT at Week 52.
The Lund-Mackay score scoring system is used to provide a quantitative assessment of nasal sinuses on sinus CT scans. Based on the sinus CT images, the five sinuses (maxillary, anterior ethmoid, posterior ethmoid, sphenoid and frontal) on each site are score by central radiologist as follows: (0-Normal; 1-Partial Opacification; 2-Total Opacification). The osteomeatal complex is scored for right and left sides (0 - Not occluded; 2- Occluded). The total score ranges from 0 to 24 (higher scores indicate poorer outcomes).
Time frame: Week 52
Percentage of Participants With Nasal Polyp Surgery Decision and/or Systemic Corticosteroid for Nasal Polyposis up to Week 52
Surgery is defined as any procedure involving instruments resulting in incision and removal of tissue (e.g., polypectomy, endoscopic sinus surgery). Rescue treatment of NP is defined as requiring treatment with systemic corticosteroids (SCS) for at least 3 consecutive days (a single depo-injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids). Time to first NP surgery decision or SCS for NP = (date of the first NP surgery decision or start date of first SCS for NP use - date of randomisation)+1. Kaplan Meier estimates of percentage of participants with events and 95% confidence interval are provided for each treatment group.
Time frame: Up to Week 52
Percentage of Participants With Nasal Polyp Surgery Decision up to Week 52
Surgery is defined as any procedure involving instruments resulting in incision and removal of tissue (e.g., polypectomy, endoscopic sinus surgery). Time to first NP surgery decision = (date of the first NP surgery decision - date of randomisation)+1. Kaplan Meier estimates of percentage of participants with events and 95% confidence interval are provided for each treatment group.
Time frame: Up to Week 52
Percentage of Participants With Systemic Corticosteroids for Nasal Polyposis up to Week 52
Systemic corticosteroids (SCS) for nasal polyposis (NP) is defined as requiring at least 3 consecutive days (a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of SCS) for NP. Time to first SCS for NP = (start date of first SCS for NP use - date of randomisation)+1. Kaplan Meier estimates of percentage of participants with events and 95% confidence interval are provided for each treatment group.
Time frame: Up to Week 52
Change From Baseline in Bi-weekly Mean Nasal Polyposis Symptom Diary Total Symptom Score at Week 52
The participant completed the nasal polyposis symptom diary each morning throughout the study. The participant was asked to consider their experience with nasal polyposis/nasal polyps over the past 24 hours when responding to each question. Participants were asked to report their experience with nasal polyposis symptoms (nasal blockage, nasal congestion, runny nose, postnasal drip (mucus drainage down the throat), headache, facial pain, facial pressure, difficulty with sense of smell). Participants reported the severity of each symptom and symptom impact at its worst using a 4-point verbal rating scale (0-None to 3-Severe). A total symptom score (range from 0 to 24) was calculated by taking the sum of the 8 equally weighted symptom items. Higher scores indicate greater symptom severity.
Time frame: Baseline to Week 52
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume (L) in 1 Second at Week 52.
For participants with comorbid asthma and aspirin exacerbated respiratory disease (AERD)/nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NSAID-ERD), difference in change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) in the tezepelumab arm as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of forced expiration.
Time frame: Baseline to Week 52