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 (WAYPOINT)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 416
- 试验地点
- 112
- 主要终点
- Change From Baseline in Total Nasal Polyp Score at Week 52
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-Blind
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with physician-diagnosed CRSwNP for at least 12 months prior to Visit 1 that have:
- •Severity consistent with need for surgery as defined by total NPS ≥ 5 (≥ 2 for each nostril) at screening, as determined by the central reader
- •Nasal Congestion Score (NCS) ≥ 2 at Visit 1
- •Ongoing documented NP symptoms over > 8 weeks prior to screening such as rhinorrhea and/or reduction/loss of smell
- •SNOT-22 total score ≥ 30 at screening (Visit 1)
- •Any standard of care for treatment of CRSwNP provided the participant is stable on that treatment for 30 days prior to Visit 1
- •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)
排除标准
- •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.
- •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.
- •Positive COVID-19 PCR test (or COVID-19 rapid test) or COVID-19 entry screening questionnaire during the screening visit. Evaluation will be based on on local standard of care as determined by current local guidelines.
- •Regular use of decongestants (topical or systematic) at enrolment is not allowed unless used for endoscopic procedure
- •Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine, hydroxychloroquine, systemic corticosteroids 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).
- •Receipt of COVID-19 vaccine (regardless of vaccine delivery platform) 28 days prior to date of IP administration at Visit 3 (randomisation visit).
研究组 & 干预措施
Placebo
Placebo subcutaneous injection in an accessorized pre-filled syringe Q4W added to background MFNS or equivalent INCS.
干预措施: Placebo (Other)
Tezepelumab
Tezepelumab subcutaneous injection in an accessorized pre-filled syringe every 4 weeks (Q4W) added to background mometasone furoate (MFNS) or equivalent intranasal corticosteroid (INCS).
干预措施: Experimental: Tezepelumab (Biological)
Tezepelumab
Tezepelumab subcutaneous injection in an accessorized pre-filled syringe every 4 weeks (Q4W) added to background mometasone furoate (MFNS) or equivalent intranasal corticosteroid (INCS).
干预措施: Mometasone furoate or equivalent intranasal corticosteroid (Drug)
Placebo
Placebo subcutaneous injection in an accessorized pre-filled syringe Q4W added to background MFNS or equivalent INCS.
干预措施: Mometasone furoate or equivalent intranasal corticosteroid (Drug)
结局指标
主要结局
Change From Baseline in Total Nasal Polyp Score at Week 52
时间窗: Baseline to 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.
Change From Baseline in Bi-weekly Mean Nasal Congestion Score (NCS) at Week 52
时间窗: Baseline to 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.
次要结局
- Nasal Polyp-Quality of Life Compared with Placebo(Baseline to Week 52)
- Nasal Polyposis Surgery and/or Receiving Systemic Corticosteroids for Nasal Polyposis(Up to Week 52)
- Sinus Opacification(Baseline to Week 52)
- Nasal Polyposis Symptom Diary Total Symptom Score(Baseline to Week 52)
- Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) in Participants with Comorbid Asthma and Aspirin Exacerbated Respiratory Disease (AERD)/Nonsteroidal Anti-Inflammatory Drug Exacerbated Respiratory Disease (NSAID-ERD)(Baseline to Week 52)
- Change From Baseline in Bi-weekly Mean Loss of Smell at Week 52(Baseline to Week 52)
- Change From Baseline in SinoNasal Outcome Test 22 (SNOT-22) at Week 52(Baseline to Week 52)
- Change From Baseline in Lund Mackay Score Evaluated by CT at Week 52.(Week 52)
- Percentage of Participants With Nasal Polyp Surgery Decision and/or Systemic Corticosteroid for Nasal Polyposis up to Week 52(Up to Week 52)
- Percentage of Participants With Nasal Polyp Surgery Decision up to Week 52(Up to Week 52)
- Percentage of Participants With Systemic Corticosteroids for Nasal Polyposis up to Week 52(Up to Week 52)
- Change From Baseline in Bi-weekly Mean Nasal Polyposis Symptom Diary Total Symptom Score at Week 52(Baseline to Week 52)
- Change From Baseline in Pre-bronchodilator Forced Expiratory Volume (L) in 1 Second at Week 52.(Baseline to Week 52)