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

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)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps
• Intervention / Treatment: Biological: Experimental: Tezepelumab; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 416
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Canada
  • Quebec, Canada, G1V 4W2
    • Research Site
  • Quebec, Canada, G1V 4G5
    • Research Site
  • Quebec, Canada, G1S 4L8
    • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8S 1G5
      • Research Site
    • London, Ontario, Canada, N6A 4V2
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Site
    • Montreal, Quebec, Canada, H3G 1L5
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    • Montreal, Quebec, Canada, H2X 3E4
      • Research Site
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • Research Site
• China
  • Bengbu, China, 233060
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  • Chengdu, China, 610072
    • Research Site
  • Guangzhou, China, 510120
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  • Hangzhou, China, 310003
    • Research Site
  • Hangzhou, China, 310014
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  • Hengyang, China, 50012
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  • Lanzhou, China, 730030
    • Research Site
  • Nanchang, China, 330006
    • Research Site
  • Nanjing, China, 210009
    • Research Site
  • Qingdao, China, 266011
    • Research Site
  • Shanghai, China, 200433
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  • Shanghai, China, 200031
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  • Suzhou, China, 215006
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  • Taizhou, China, 225300
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  • Tianjin, China, 300211
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  • Tianjin, China, 300121
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  • Wenzhou, China, 325027
    • Research Site
  • Wu Han, China, 430060
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  • Xi'An, China, 710068
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  • Yinchuan, China, 750001
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  • Zunyi, China, 563100
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• Denmark
  • Aarhus N, Denmark, 8200
    • Research Site
  • Hillerød, Denmark, 3400
    • Research Site
  • Hvidovre, Denmark, 2650
    • Research Site
  • København NV, Denmark, 2400
    • Research Site
  • Køge, Denmark, 4600
    • Research Site
  • Odense, Denmark, 5000
    • Research Site
  • Vejle, Denmark, 7100
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  • Ålborg, Denmark, 9000
    • Research Site
• Germany
  • Berlin, Germany, 10629
    • Research Site
  • Berlin, Germany, 13353
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  • Dresden, Germany, 01307
    • Research Site
  • Heidelberg, Germany, 69120
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  • Lübeck, Germany, 23538
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  • Marburg, Germany, 35043
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  • Tübingen, Germany, 72076
    • Research Site
  • Wiesbaden, Germany, 65183
    • Research Site
• Hungary
  • Budapest, Hungary, 1083
    • Research Site
  • Budapest, Hungary, 1134
    • Research Site
  • Budapest, Hungary, 1046
    • Research Site
  • Nyíregyháza, Hungary, 4400
    • Research Site
  • Pécs, Hungary, 7621
    • Research Site
  • Siófok, Hungary, 8600
    • Research Site
  • Székesfehérvár, Hungary, 8000
    • Research Site
• Japan
  • Bunkyo-ku, Japan, 113-8431
    • Research Site
  • Chuo-shi, Japan, 409-3898
    • Research Site
  • Habikino-shi, Japan, 583-0886
    • Research Site
  • Ichikawa-shi, Japan, 272-0111
    • Research Site
  • Itabashi-ku, Japan, 173-8610
    • Research Site
  • Kashiwa-shi, Japan, 277-0882
    • Research Site
  • Kisarazu-shi, Japan, 292-8535
    • Research Site
  • Miyazaki-shi, Japan, 880-8510
    • Research Site
  • Nagaoka-shi, Japan, 940-8621
    • Research Site
  • Nerima-ku, Japan, 177-0035
    • Research Site
  • Niigata-shi, Japan, 951-8520
    • Research Site
  • Osaka-shi, Japan, 553-0003
    • Research Site
  • Saitama-shi, Japan, 336-8522
    • Research Site
  • Sapporo-shi, Japan, 003-0022
    • Research Site
  • Sendai-shi, Japan, 983-8512
    • Research Site
  • Suwa-shi, Japan, 392-8510
    • Research Site
  • Toyonaka Shi, Japan, 560-0082
    • Research Site
  • Yokohama-shi, Japan, 227-8501
    • Research Site
  • Yokohama-shi, Japan, 236-0037
    • Research Site
• Poland
  • Bialystok, Poland, 15-879
    • Research Site
  • Bydgoszcz, Poland, 85-231
    • Research Site
  • Kraków, Poland, 31-513
    • Research Site
  • Nadarzyn, Poland, 05-830
    • Research Site
  • Wrocław, Poland, 53-301
    • Research Site
  • Wrocław, Poland, 50-556
    • Research Site
  • Zawadzkie, Poland, 47-120
    • Research Site
  • Łodź, Poland, 90-153
    • Research Site
• Spain
  • Barakaldo, Spain, 48903
    • Research Site
  • Barcelona, Spain, 08036
    • Research Site
  • Jerez de la Frontera, Spain, 11407
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Santiago de Compostela, Spain, 15706
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  • Sevilla, Spain, 41009
    • Research Site
• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Research Site
  • London, United Kingdom, SE1 9RT
    • Research Site
  • Manchester, United Kingdom, M13 9WL
    • Research Site
  • Stockport, United Kingdom
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Research Site
  • California
    • Bakersfield, California, United States, 93301
      • Research Site
    • Newport Beach, California, United States, 92663
      • Research Site
    • Roseville, California, United States, 95661
      • Research Site
    • Walnut Creek, California, United States, 94598
      • Research Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80923
      • Research Site
    • Denver, Colorado, United States, 80230
      • Research Site
  • Florida
    • Boca Raton, Florida, United States, 33487
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Research Site
    • White Marsh, Maryland, United States, 21162
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Research Site
  • New York
    • New York, New York, United States, 10003
      • Research Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Research Site
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Research Site
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Research Site
  • Washington
    • Spokane, Washington, United States, 99201
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53228
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tezepelumab; Tezepelumab subcutaneous injection, in an accessorized pre-filled syringe.	Biological: Experimental: Tezepelumab; Tezepelumab subcutaneous injection; Other Names: Tezepelumab
Placebo Comparator: Placebo; Placebo subcutaneous injection, in an accessorized pre-filled syringe.	Other: Placebo; Placebo subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Systemic Corticosteroid Use	Exposure of systemic corticosteroids over 52 Weeks.	Over 52 weeks
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
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
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
Serum trough concentrations	Serum trough concentrations at each scheduled visit.	Baseline to Week 52
Immunogenicity anti-drug antibodies	Incidence of anti-drug antibodies (ADA) over 52 weeks.	Baseline to Week 52

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Amgen
• Investigators: Principal Investigator: Joseph K Han, MD, Eastern Virginia Medical School; Principal Investigator: Brian Lipworth, MD, University of Dundee

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2021
• Primary Completion (Estimated): October 4, 2024
• Study Completion (Estimated): December 27, 2024

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: April 19, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Chronic rhinosinusitis with nasal polyps; Nasal polyps; Nasal polyposis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Paranasal Sinus Diseases; Nose Diseases; Polyps; Rhinitis; Sinusitis; Nasal Polyps; Rhinosinusitis; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: D5242C00001; 2020-003062-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No