Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis

Chronic Rhinosinusitis With Nasal Polyps Clinical Trial

— WAYPOINT  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04851964
• Other study ID #: D5242C00001
• Secondary ID: 2020-003062-39
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 22, 2021
• Est. completion date: December 27, 2024

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 416
• Est. completion date: December 27, 2024
• Est. primary completion date: October 4, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Chronic Rhinosinusitis With Nasal Polyps
• Nasal Polyps
• Rhinosinusitis
• Sinusitis

Intervention

Biological:
• Experimental: Tezepelumab
Tezepelumab subcutaneous injection

Other:
• Placebo
Placebo subcutaneous injection

Locations

Country	Name	City	State
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Trois-Rivières	Quebec
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Bengbu
China	Research Site	Chengdu
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hengyang
China	Research Site	Lanzhou
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Suzhou
China	Research Site	Taizhou
China	Research Site	Tianjin
China	Research Site	Tianjin
China	Research Site	Wenzhou
China	Research Site	Wu Han
China	Research Site	Xi'An
China	Research Site	Yinchuan
China	Research Site	Zunyi
Denmark	Research Site	Aarhus N
Denmark	Research Site	Ålborg
Denmark	Research Site	Hillerød
Denmark	Research Site	Hvidovre
Denmark	Research Site	København NV
Denmark	Research Site	Køge
Denmark	Research Site	Odense
Denmark	Research Site	Vejle
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Dresden
Germany	Research Site	Heidelberg
Germany	Research Site	Lübeck
Germany	Research Site	Marburg
Germany	Research Site	Tübingen
Germany	Research Site	Wiesbaden
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Siófok
Hungary	Research Site	Székesfehérvár
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chuo-shi
Japan	Research Site	Habikino-shi
Japan	Research Site	Ichikawa-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Kashiwa-shi
Japan	Research Site	Kisarazu-shi
Japan	Research Site	Miyazaki-shi
Japan	Research Site	Nagaoka-shi
Japan	Research Site	Nerima-ku
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Saitama-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Suwa-shi
Japan	Research Site	Toyonaka Shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Kraków
Poland	Research Site	Lodz
Poland	Research Site	Nadarzyn
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Poland	Research Site	Zawadzkie
Spain	Research Site	Barakaldo
Spain	Research Site	Barcelona
Spain	Research Site	Jerez de la Frontera
Spain	Research Site	Madrid
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Sevilla
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Stockport
United States	Research Site	Bakersfield	California
United States	Research Site	Baltimore	Maryland
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boca Raton	Florida
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chicago	Illinois
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Columbia	Missouri
United States	Research Site	Dallas	Texas
United States	Research Site	Denver	Colorado
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	New York	New York
United States	Research Site	Newport Beach	California
United States	Research Site	Norfolk	Virginia
United States	Research Site	North Charleston	South Carolina
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Roseville	California
United States	Research Site	Spokane	Washington
United States	Research Site	Walnut Creek	California
United States	Research Site	White Marsh	Maryland
United States	Research Site	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Amgen

Countries where clinical trial is conducted

United States,  Canada,  China,  Denmark,  Germany,  Hungary,  Japan,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Nasal Polyp Score	Change from baseline over time in Nasal Polyp Score through Week 52. The Nasal Polyp Score is the sum of the right and left nostril scores (maximum 8), as evaluated by nasal endoscopy.	Baseline to Week 52
Other	Nasal Polyp Score	Proportion of participants with (i) =1 point reduction and (ii) =2 points reduction in the Nasal Polyp Score at Week 52. The Nasal Polyp Score is the sum of the right and left nostril scores (maximum 8), as evaluated by nasal endoscopy.	Baseline to Week 52
Other	Participant Reported Nasal Congestion	Change from baseline over time in bi-weekly mean Nasal Congestion Score evaluated by Nasal Polyposis Symptom Diary through Week 52. Nasal Congestion Score is captured by asking participants to rate the severity of their worst nasal congestion over the past 24 hours (0-None; 1-Mild; 2-Moderate; 3-Severe).	Baseline to Week 52
Other	Loss of Smell	Change from baseline in loss of smell evaluated by University of Pennsylvania Smell Identification Test (UPSIT) at Week 52. The University of Pennsylvania Smell Identification Test is a quantitative test of olfactory function which uses microencapsulated odorants that are released by scratching standardized odour-impregnated test booklets. Scores are based on number of correctly identified odours (score range 0-40).	Baseline to Week 52
Other	Sinus Opacification	Change from baseline in Modified Lund Mackay score evaluated by CT at Week 52. The Modified Lund-Mackay score scoring system is used to provide a semi-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: (0-0% Opacification; 1-1-25% Opacification; 2-26-50% Opacification; 3-51-75% Opacification; 4-76-99% Opacification; 5-100% Opacification). The osteomeatal complex is scored for right and left sides (0 - Not occluded; 2- Occluded). The maximum total Modified Lund Mackay score is 50, 54 when including the Osteomeatal complex score.	Baseline to Week 52
Other	Systemic Corticosteroid Use	Exposure of systemic corticosteroids over 52 Weeks.	Over 52 weeks
Other	Nasal Polyposis Symptom Diary	Change from baseline by domain of the Nasal Polyposis Symptom Diary through Week 52. The participant will complete an 11-item nasal polyposis symptom diary each morning throughout the screening, treatment and follow-up periods. The participant is asked to consider their experience with nasal polyposis/nasal polyps over the past 24 hours when responding to each question. Participants are 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, and difficulty with sense of smell) and symptom impacts (difficulty with sleeping due to nasal symptoms and difficulty with daily activities due to nasal symptoms). Participants report the severity of each symptom and symptom impact at its worst using a 4-point verbal rating scale (0-None to 3-Severe).	Baseline to Week 52
Other	Nasal Peak Inspiratory Flow	Change from baseline in Nasal Peak Inspiratory Flow through Week 52. Nasal peak inspiratory flow evaluation represents a physiologic measure of the air flow through both nasal cavities during forced inspiration expressed in liters per minute.	Baseline to Week 52
Other	Asthma Control in Participants with Comorbid Asthma and Aspirin Exacerbated Respiratory Disease (AERD)/Nonsteroidal Anti-Inflammatory Drug Exacerbated Respiratory Disease (NSAID-ERD)	Change from baseline in Asthma Control Questionnaire-6 at Week 52. The Asthma Control Questionnaire is an assessment of asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short acting beta-agonist use). Participants are asked to recall their level of asthma control during the previous week by responding to one bronchodilator use question and 5 symptom questions. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled).	Baseline to Week 52
Other	Serum trough concentrations	Serum trough concentrations at each scheduled visit.	Baseline to Week 52
Other	Immunogenicity anti-drug antibodies	Incidence of anti-drug antibodies (ADA) over 52 weeks.	Baseline to Week 52
Primary	Nasal Polyp Score	Change from baseline in total Nasal Polyp Score at Week 52. The Nasal Polyp Score is the sum of the right and left nostril scores (maximum 8), as evaluated by nasal endoscopy.	Baseline to Week 52
Primary	Participant Reported Nasal Congestion	Change from baseline in bi-weekly mean Nasal Congestion score evaluated as part of the Nasal Polyposis Symptom Diary at Week 52. Nasal Congestion Score is captured by asking participants to rate the severity of their worst nasal congestion over the past 24 hours (0-None; 1-Mild; 2-Moderate; 3-Severe).	Baseline to Week 52
Secondary	Loss of Smell	Change from baseline in bi-weekly mean loss of smell evaluated by the Nasal Polyposis Symptom Diary by asking patients to rate the severity of their worst difficulty with sense of smell over the past 24 hours at week 52. Response options include: 0- None; 1- Mild; 2- Moderate; 3- Severe.	Baseline to Week 52
Secondary	Nasal Polyp-Quality of Life Compared with Placebo	Change from baseline in SinoNasal Outcome Test 22 (SNOT-22) scores 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).	Baseline to Week 52
Secondary	Nasal Polyposis Surgery and/or Receiving Systemic Corticosteroids for Nasal Polyposis	Time to surgery decision and/or systemic corticosteroids for nasal polyposis, time to nasal polyposis surgery decision, and time to systemic corticosteroids for nasal polyposis up to Week 52.	Up to Week 52
Secondary	Sinus Opacification	Change from baseline in Lund Mackay score evaluated by CT, sinus severity score by quantitative CT assessment, 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).	Baseline to Week 52
Secondary	Nasal Polyposis Symptom Diary Total Symptom Score	Change from baseline in bi-weekly mean Nasal Polyposis Symptom Diary Total Symptom Score at Week 52. The participant will complete an 11-item nasal polyposis symptom diary each morning throughout the screening, treatment and followup periods. The participant is asked to consider their experience with nasal polyposis/nasal polyps over the past 24hrs when responding to each question. Participants are 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) and symptom impacts (difficulty with sleeping due to nasal symptoms and difficulty with daily activities due to nasal symptoms). Participants report 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 is calculated by taking the sum of the 8 equally weighted symptom items.	Baseline to Week 52
Secondary	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)	Change from baseline in pre-bronchodilator forced expiratory volume 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.	Baseline to Week 52