Clinical trial NCT04851964: Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Keywords: Chronic rhinosinusitis with nasal polyps
Nasal polyps
Nasal polyposis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2021-04-21
Enrollment: 416
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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. Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection using the accessorized pre-filled syringe (APFS), 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.

Eligibility criteria: Inclusion Criteria:

1. Participants with physician-diagnosed CRSwNP for at least 12 months prior to Visit 1 that have:

   1. Severity consistent with need for surgery as defined by total NPS ≥ 5 (≥ 2 for each nostril) at screening, as determined by the central reader
   2. Nasal Congestion Score (NCS) ≥ 2 at Visit 1
   3. 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)

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. Evaluation will be based on on local standard of care as determined by current local guidelines.
4. Regular use of decongestants (topical or systematic) 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 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 Visit 3 (randomisation visit).

Primary outcomes:
measure: Nasal Polyp Score
timeFrame: Baseline to Week 52
measure: Participant Reported Nasal Congestion
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Loss of Smell
timeFrame: Baseline to Week 52
measure: Nasal Polyp-Quality of Life Compared with Placebo
timeFrame: Baseline to Week 52
measure: Nasal Polyposis Surgery and/or Receiving Systemic Corticosteroids for Nasal Polyposis
timeFrame: Up to Week 52
measure: Sinus Opacification
timeFrame: Baseline to Week 52
measure: Nasal Polyposis Symptom Diary Total Symptom Score
timeFrame: Baseline to Week 52
measure: 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)
timeFrame: Baseline to Week 52
Other outcomes:
measure: Nasal Polyp Score
timeFrame: Baseline to Week 52
measure: Nasal Polyp Score
timeFrame: Baseline to Week 52
measure: Participant Reported Nasal Congestion
timeFrame: Baseline to Week 52
measure: Loss of Smell
timeFrame: Baseline to Week 52
measure: Sinus Opacification
timeFrame: Baseline to Week 52
measure: Systemic Corticosteroid Use
timeFrame: Over 52 weeks
measure: Nasal Polyposis Symptom Diary
timeFrame: Baseline to Week 52
measure: Nasal Peak Inspiratory Flow
timeFrame: Baseline to Week 52
measure: Asthma Control in Participants with Comorbid Asthma and Aspirin Exacerbated Respiratory Disease (AERD)/Nonsteroidal Anti-Inflammatory Drug Exacerbated Respiratory Disease (NSAID-ERD)
timeFrame: Baseline to Week 52
measure: Serum trough concentrations
timeFrame: Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, and Week 64
measure: Immunogenicity anti-drug antibodies
timeFrame: Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, and Week 64
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Roseville
country: United States
facility: Research Site
state: California
city: Walnut Creek
country: United States
facility: Research Site
state: California
city: Colorado Springs
country: United States
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state: Colorado
city: Denver
country: United States
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state: Colorado
city: Boca Raton
country: United States
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state: Florida
city: Chicago
country: United States
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state: Illinois
city: Baltimore
country: United States
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state: Maryland
city: White Marsh
country: United States
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state: Maryland
city: Boston
country: United States
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state: Massachusetts
city: Columbia
country: United States
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state: Missouri
city: New York
country: United States
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state: New York
city: Winston-Salem
country: United States
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state: North Carolina
city: Oklahoma City
country: United States
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state: Oklahoma
city: North Charleston
country: United States
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state: South Carolina
city: Dallas
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state: Texas
city: Norfolk
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state: Virginia
city: Spokane
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state: Washington
city: Milwaukee
country: United States
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state: Wisconsin
city: Vancouver
country: Canada
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state: British Columbia
city: Hamilton
country: Canada
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state: Ontario
city: London
country: Canada
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state: Ontario
city: Montreal
country: Canada
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state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
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state: Quebec
city: Trois-Rivières
country: Canada
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state: Quebec
city: Quebec
country: Canada
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city: Quebec
country: Canada
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city: Quebec
country: Canada
facility: Research Site
city: Bengbu
country: China
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city: Chengdu
country: China
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city: Guangzhou
country: China
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city: Hangzhou
country: China
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city: Hangzhou
country: China
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city: Hengyang
country: China
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city: Lanzhou
country: China
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city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
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city: Qingdao
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
facility: Research Site
city: Suzhou
country: China
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city: Taizhou
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wu Han
country: China
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city: Xi'An
country: China
facility: Research Site
city: Yinchuan
country: China
facility: Research Site
city: Zunyi
country: China
facility: Research Site
city: Aarhus N
country: Denmark
facility: Research Site
city: Hillerød
country: Denmark
facility: Research Site
city: Hvidovre
country: Denmark
facility: Research Site
city: København NV
country: Denmark
facility: Research Site
city: Køge
country: Denmark
facility: Research Site
city: Odense
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Ålborg
country: Denmark
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city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
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city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Siófok
country: Hungary
facility: Research Site
city: Székesfehérvár
country: Hungary
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chuo-shi
country: Japan
facility: Research Site
city: Habikino-shi
country: Japan
facility: Research Site
city: Ichikawa-shi
country: Japan
facility: Research Site
city: Itabashi-ku
country: Japan
facility: Research Site
city: Kashiwa-shi
country: Japan
facility: Research Site
city: Kisarazu-shi
country: Japan
facility: Research Site
city: Miyazaki-shi
country: Japan
facility: Research Site
city: Nagaoka-shi
country: Japan
facility: Research Site
city: Nerima-ku
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Saitama-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Suwa-shi
country: Japan
facility: Research Site
city: Toyonaka Shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Nadarzyn
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Zawadzkie
country: Poland
facility: Research Site
city: Łodź
country: Poland
facility: Research Site
city: Barakaldo
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Jerez de la Frontera
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Stockport
country: United Kingdom
facility: Research Site
Study officials:
affiliation: University of Dundee
name: Brian Lipworth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Eastern Virginia Medical School
name: Joseph K Han, MD
role: PRINCIPAL_INVESTIGATOR
References: