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)
2 other identifiers
interventional
416
10 countries
112
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Apr 2021
Typical duration for phase_3
112 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 18, 2021
CompletedFirst Posted
Study publicly available on registry
April 21, 2021
CompletedStudy Start
First participant enrolled
April 22, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 23, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 11, 2024
CompletedResults Posted
Study results publicly available
January 27, 2026
CompletedJanuary 27, 2026
January 1, 2026
3.4 years
February 18, 2021
September 12, 2025
January 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Change From Baseline in Total Nasal Polyp Score at 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.
Baseline to Week 52
Change From Baseline in Bi-weekly Mean Nasal Congestion Score (NCS) at 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.
Baseline to Week 52
Secondary Outcomes (8)
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
- +3 more secondary outcomes
Other Outcomes (14)
Change From Baseline Over Time in Nasal Polyp Score Through Week 52.
Baseline to Week 52
Proportion of Participants With ≥1 Point Reduction in the Nasal Polyp Score at Week 52
Baseline to Week 52
Proportion of Participants With ≥2 Point Reduction in the Nasal Polyp Score at Week 52
Baseline to Week 52
- +11 more other outcomes
Study Arms (2)
Tezepelumab
EXPERIMENTALTezepelumab subcutaneous injection in an accessorized pre-filled syringe every 4 weeks (Q4W) added to background mometasone furoate (MFNS) or equivalent intranasal corticosteroid (INCS).
Placebo
PLACEBO COMPARATORPlacebo subcutaneous injection in an accessorized pre-filled syringe Q4W added to background MFNS or equivalent INCS.
Interventions
Background MFNS or equivalent INCS at stable dose
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Amgencollaborator
Study Sites (112)
Research Site
Birmingham, Alabama, 35209, United States
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Bakersfield, California, 93301, United States
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Newport Beach, California, 92663, United States
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Roseville, California, 95661, United States
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Walnut Creek, California, 94598, United States
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Colorado Springs, Colorado, 80923, United States
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Denver, Colorado, 80230, United States
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Boca Raton, Florida, 33487, United States
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Chicago, Illinois, 60657, United States
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Baltimore, Maryland, 21224, United States
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White Marsh, Maryland, 21162, United States
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Boston, Massachusetts, 02115, United States
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Columbia, Missouri, 65212, United States
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New York, New York, 10003, United States
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Winston-Salem, North Carolina, 27103, United States
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Oklahoma City, Oklahoma, 73120, United States
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North Charleston, South Carolina, 29406, United States
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Dallas, Texas, 75231, United States
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Norfolk, Virginia, 23507, United States
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Spokane, Washington, 99201, United States
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Milwaukee, Wisconsin, 53228, United States
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Vancouver, British Columbia, V6Z 1Y6, Canada
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Hamilton, Ontario, L8S 1G5, Canada
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London, Ontario, N6A 4V2, Canada
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Montreal, Quebec, H2V 2K1, Canada
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Montreal, Quebec, H2X 0A9, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Québec, Quebec, G1S 4L8, Canada
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Québec, Quebec, G1V 4G5, Canada
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Québec, Quebec, G1V 4W2, Canada
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Trois-Rivières, Quebec, G8T 7A1, Canada
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Bengbu, 233004, China
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Chengdu, 610072, China
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Guangzhou, 510120, China
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Hangzhou, 310003, China
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Hangzhou, 310014, China
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Hengyang, 421001, China
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Lanzhou, 730030, China
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Nanchang, 330006, China
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Nanjing, 210009, China
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Qingdao, 266011, China
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Shanghai, 200031, China
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Shanghai, 200433, China
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Suzhou, 215006, China
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Taizhou, 225300, China
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Tianjin, 300121, China
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Tianjin, 300211, China
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Wenzhou, 325027, China
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Wuhan, 430060, China
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Xi'an, 710068, China
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Yinchuan, 750001, China
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Zunyi, 563100, China
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Aalborg, 9000, Denmark
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Aarhus N, 8200, Denmark
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Hillerød, 3400, Denmark
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Hvidovre, 2650, Denmark
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København NV, 2400, Denmark
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Køge, 4600, Denmark
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Odense, 5000, Denmark
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Vejle, 7100, Denmark
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Berlin, 10629, Germany
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Berlin, 13353, Germany
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Dresden, 01307, Germany
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Heidelberg, 69120, Germany
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Lübeck, 23538, Germany
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Marburg, 35043, Germany
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Tübingen, 72076, Germany
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Wiesbaden, 65183, Germany
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Budapest, 1046, Hungary
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Budapest, 1083, Hungary
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Budapest, 1134, Hungary
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Nyíregyháza, 4400, Hungary
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Pécs, 7621, Hungary
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Siófok, 8600, Hungary
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Székesfehérvár, 8000, Hungary
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Bunkyō City, 113-8431, Japan
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Chuo-shi, 409-3898, Japan
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Habikino-shi, 583-0886, Japan
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Ichikawa-shi, 272-0111, Japan
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Itabashi-ku, 173-8610, Japan
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Kashiwa-shi, 277-0882, Japan
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Kisarazu-shi, 292-8535, Japan
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Miyazaki, 880-8510, Japan
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Nagaoka-shi, 940-8621, Japan
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Nerima-ku, 177-0035, Japan
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Niigata, 951-8520, Japan
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Osaka, 553-0003, Japan
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Saitama-shi, 336-8522, Japan
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Sapporo, 003-0022, Japan
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Sendai, 983-8512, Japan
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Suwa-shi, 392-8510, Japan
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Toyonaka Shi, 560-0082, Japan
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Yokohama, 227-8501, Japan
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Yokohama, 236-0037, Japan
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Bialystok, 15-879, Poland
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Bydgoszcz, 85-231, Poland
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Krakow, 31-513, Poland
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Nadarzyn, 05-830, Poland
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Wroclaw, 50-556, Poland
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Wroclaw, 53-301, Poland
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Zawadzkie, 47-120, Poland
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Łodź, 90-153, Poland
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Barakaldo, 48903, Spain
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Barcelona, 08036, Spain
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Jerez de la Frontera, 11407, Spain
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Madrid, 28040, Spain
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Santiago de Compostela, 15706, Spain
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Seville, 41009, Spain
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Dundee, DD1 9SY, United Kingdom
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London, SE1 9RT, United Kingdom
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Manchester, M13 9WL, United Kingdom
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Stockport, SK2 7JE, United Kingdom
Related Publications (1)
Lipworth BJ, Han JK, Desrosiers M, Hopkins C, Lee SE, Mullol J, Pfaar O, Li T, Chen C, Almqvist G, Margolis MK, McLaren J, Jagadeesh S, MacKay J, Megally A, Hellqvist A, Mankad VS, Bahadori L, Ponnarambil SS; WAYPOINT Study Investigators. Tezepelumab in Adults with Severe Chronic Rhinosinusitis with Nasal Polyps. N Engl J Med. 2025 Mar 27;392(12):1178-1188. doi: 10.1056/NEJMoa2414482. Epub 2025 Mar 1.
PMID: 40106374DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
Brian Lipworth, MD
University of Dundee
- PRINCIPAL INVESTIGATOR
Joseph K Han, MD
Eastern Virginia Medical School
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Double-Blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 18, 2021
First Posted
April 21, 2021
Study Start
April 22, 2021
Primary Completion
September 23, 2024
Study Completion
December 11, 2024
Last Updated
January 27, 2026
Results First Posted
January 27, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, 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.
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.