Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT)
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| ClinicalTrials.gov Identifier: NCT04851964 |
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Recruitment Status :
Recruiting
First Posted : April 21, 2021
Last Update Posted : May 31, 2023
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Sponsor:
AstraZeneca
Collaborator:
Amgen
Information provided by (Responsible Party):
AstraZeneca
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Rhinosinusitis With Nasal Polyps | Biological: Experimental: Tezepelumab Other: Placebo | Phase 3 |
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 (Clinical Trial) |
| Estimated Enrollment : | 400 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously. |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Double-Blind |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | April 22, 2021 |
| Estimated Primary Completion Date : | August 2, 2024 |
| Estimated Study Completion Date : | October 25, 2024 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Tezepelumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Tezepelumab
Tezepelumab subcutaneous injection, in an accessorized pre-filled syringe.
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Biological: Experimental: Tezepelumab
Tezepelumab subcutaneous injection
Other Name: Tezepelumab |
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Placebo Comparator: Placebo
Placebo subcutaneous injection, in an accessorized pre-filled syringe.
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Other: Placebo
Placebo subcutaneous injection |
Primary Outcome Measures :
- Nasal Polyp Score [ Time Frame: Baseline to Week 52 ]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.
- Participant Reported Nasal Congestion [ Time Frame: Baseline to Week 52 ]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).
Secondary Outcome Measures :
- Loss of Smell [ Time Frame: Baseline to Week 52 ]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.
- Nasal Polyp-Quality of Life Compared with Placebo [ Time Frame: Baseline to Week 52 ]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).
- Nasal Polyposis Surgery and/or Receiving Systemic Corticosteroids for Nasal Polyposis [ Time Frame: Up to Week 52 ]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.
- Sinus Opacification [ Time Frame: Baseline to Week 52 ]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).
- Nasal Polyposis Symptom Diary Total Symptom Score [ Time Frame: Baseline to Week 52 ]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.
- Resolution/Near Complete Resolution of Nasal Polyps (defined as maximum NPS of 1 in each nostril) [ Time Frame: At Week 52 ]Proportion of participants who achieve a maximum NPS of 1 in each nostril at Week 52.
- Resolution/Near Complete Resolution of Nasal Polyps (defined as maximum NPS of 1 in each nostril) and Nasal Polyposis Symptom Diary Total Symptom Score response [ Time Frame: At Week 52 ]Proportion of participants who achieve a maximum NPS of 1 in each nostril and Nasal Polyposis Symptom Diary Total Symptom Score response at 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) [ Time Frame: Baseline to Week 52 ]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.
Other Outcome Measures:
- Nasal Polyp Score [ Time Frame: Baseline to Week 52 ]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.
- Nasal Polyp Score [ Time Frame: Baseline to Week 52 ]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.
- Participant Reported Nasal Congestion [ Time Frame: Baseline to Week 52 ]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).
- Loss of Smell [ Time Frame: Baseline to Week 52 ]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).
- Sinus Opacification [ Time Frame: Baseline to Week 52 ]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.
- Systemic Corticosteroid Use [ Time Frame: Over 52 weeks ]Exposure of systemic corticosteroids over 52 Weeks.
- Nasal Polyposis Symptom Diary [ Time Frame: Baseline to Week 52 ]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).
- Nasal Peak Inspiratory Flow [ Time Frame: Baseline to Week 52 ]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.
- Asthma Control in Participants with Comorbid Asthma and Aspirin Exacerbated Respiratory Disease (AERD)/Nonsteroidal Anti-Inflammatory Drug Exacerbated Respiratory Disease (NSAID-ERD) [ Time Frame: Baseline to Week 52 ]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).
- Serum trough concentrations [ Time Frame: Baseline to Week 52 ]Serum trough concentrations at each scheduled visit.
- Immunogenicity anti-drug antibodies [ Time Frame: Baseline to Week 52 ]Incidence of anti-drug antibodies (ADA) over 52 weeks.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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)
Exclusion Criteria:
- 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).
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04851964
Contacts
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Locations
Show 144 study locations
Sponsors and Collaborators
AstraZeneca
Amgen
Investigators
| Principal Investigator: | Brian Lipworth, MD | University of Dundee | |
| Principal Investigator: | Joseph K Han, MD | Eastern Virginia Medical School |
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT04851964 |
| Other Study ID Numbers: |
D5242C00001 2020-003062-39 ( EudraCT Number ) |
| First Posted: | April 21, 2021 Key Record Dates |
| Last Update Posted: | May 31, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
| 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. |
| 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. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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Chronic rhinosinusitis with nasal polyps Nasal polyps Nasal polyposis |
Additional relevant MeSH terms:
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Sinusitis Nasal Polyps Polyps Pathological Conditions, Anatomical Respiratory Tract Infections Infections Paranasal Sinus Diseases |
Nose Diseases Respiratory Tract Diseases Otorhinolaryngologic Diseases Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |