Chronic Rhinosinusitis With Nasal PolypsPhase 3ESSENCENCT06706817
A Study to Investigate Changes in Symptoms in Adult Participants With Chronic Rhinosinusitis With Nasal Polyposis Initiating Treatment With Tezepelumab
A Phase 3 study testing Tezepelumab in people with Chronic Rhinosinusitis With Nasal Polyps, run by AstraZeneca at 41 sites in 9 countries.
Trial summary
The main objective of this study is to evaluate treatment outcomes of tezepelumab among participants with physician-determined surgery-eligible CRSwNP, with or without asthma. Study details include: 1. The study duration will be up to 40 weeks. 2. The treatment duration will be up to 24 weeks. 3. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Chronic Rhinosinusitis With Nasal Polyps
- What is being tested?
- Tezepelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 181 participants
- Where
- 41 sitesin 9 countries
- Study dates
- 3 Dec 2024to 13 Jan 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must be 18 years of age or older, at the time of signing the informed consent.
- Participants with physician-diagnosed CRSwNP for at least 12 months prior to Visit 1 who have all of the following:
- Severity consistent with the need for surgery as defined by total NPS ≥ 4 (at least 2 for each nostril) at screening, as determined by the central reader
- Mean NCS ≥ 2 in the 2 weeks prior to Visit 2
- Ongoing documented NP symptoms for > 8 weeks prior to screening such as rhinorrhoea, reduction or loss of smell and/or poor quality/loss of sleep
- SNOT-22 total score ≥ 30 as assessed at screening. Note: approximately 50 participants with a NPS = 4 at screening will receive treatment with tezepelumab.
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- Any standard of care for treatment of CRSwNP, which must include treatment with intranasal corticosteroids, provided the participant is stable on that treatment for at least 30 days prior to Visit 1. Investigators should also assure that participants are compliant and on a stable dose of the background INCS during study period.
- Either 1) documented treatment of NP 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 OR 2) any history of NP surgery (or contraindications/intolerance to)
- Body weight of ≥ 40 kg at Visit 1
- Female participants:
- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Women of non childbearing potential are defined as women who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal.
- Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned start date of the first IMP administration without an alternative medical cause.
- The following age-specific requirements apply:
- Women < 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and FSH levels in the postmenopausal range.
- Women ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.
- WOCBP must be willing to use one of the methods of contraception described hereafter, from the time of signing the ICF throughout the study and 16 weeks after last tezepelumab administration:
- Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
- Intrauterine device
- Intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Vasectomised partner (vasectomised partner is a highly effective birth control method provided that the partner is the sole sexual partner of the WOCBP participant and that the vasectomised partner has received medical assessment of the surgical success)
- Sexual abstinence: it is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
- Cessation of contraception after this point should be discussed with a responsible physician.
- Provision of signed and dated written ICF as described in Appendix A 3 prior to any mandatory study-specific procedures, sampling, and analyses.
- Participant who is capable of giving signed informed consent as described in Appendix A 3 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Who cannot join
- Participants with documented allergic fungal rhinosinusitis and/or central compartment atopic disease.
- Any clinically important pulmonary disease other than asthma (eg, active lung infection, bronchiectasis, pulmonary fibrosis, cystic fibrosis, primary ciliary dyskinesia, allergic bronchopulmonary mycosis, hypereosinophilic syndromes, etc) that could confound interpretation of clinical CRSwNP endpoints results.
- Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and could:
- Affect the safety of the participant throughout the study
- Influence the findings of the study or the interpretation
- Impede the participant's ability to complete the entire duration of study.
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- 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.
- Participants with conditions or concomitant disease that makes them non-evaluable for the primary CRSwNP endpoints such as:
- Antrochoanal polyps
- Nasal septal deviation that occludes at least one nostril
- Acute sinusitis, nasal infection, asthma exacerbation or upper respiratory infection at screening or in the two weeks before screening, or Churg-Strauss syndrome (also known as eosinophilic granulomatosis with polyangiitis), Young's syndrome or Kartagener's syndrome
- History of cancer:
- Participants who have had basal cell carcinoma, localised squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible to participate in the study provided that curative therapy was completed at least 12 months prior to Visit 1.
- Participants who have had other malignancies are eligible provided that curative therapy was completed at least 5 years prior to Visit 1.
- Uncontrolled epistaxis within 2 months of Visit 1
- A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not been treated with, or has failed to respond to, standard of care therapy.
- For participants with comorbid asthma: Current smokers or participants with a smoking history ≥ 10 packs per year and participants using vaping products, including electronic cigarettes. Former smokers with a smoking history of < 10 pack per year and users of vaping or e-cigarette products must have stopped for at least 6 months prior to Visit 1 to be eligible.
- History of chronic alcohol or drug abuse within 12 months prior to Visit 1.
- Tuberculosis requiring treatment within the 12 months prior to Visit 1.
- Major surgery within 8 weeks prior to Visit 1 or planned NP surgery or planned surgical procedures requiring general anaesthesia or inpatient status for more than 1 day during the conduct of the study.
- History of known immunodeficiency disorder including a positive HIV test at Visit 1, or the participant taking antiretroviral medications as determined by medical history and/or participant's verbal report.
- Infection requiring systemic antibiotics within 14 days prior to Visit 1. Note: Participants with respiratory infections requiring antibiotics within 14 days prior to Visit 1 may extend their screening period to allow recovery and return no sooner than 14 days after completion of therapy.
- Evidence of COVID-19 within 4 weeks prior to screening or ongoing clinically significant COVID-19 sequelae (eg, participants who have long-term post-COVID-19 anosmia).
- Receipt of any marketed or investigational biologic agent within 4 months or 5 half-lives (whichever is longer) prior to Visit 1 or receipt of any investigational non-biologic agent within 30 days or 5 half-lives (whichever is longest) prior to Visit 1.
- Treatment with systemic immunosuppressive/immunomodulating drugs (eg, methotrexate, cyclosporine, etc.), except for SCS used in the treatment of asthma/asthma exacerbations, within the last 12 weeks or 5 half-lives (whichever is longer) prior to Visit 1.
- Receipt of immunoglobulin or blood products within 30 days prior to Visit 1.
Trial locations and contacts
41 sites in 9 countries.
41 sites in 9 countries
Italy7 sites
Research Site
Bologna, 40139
Research Site
Catania, 95123
Research Site
Florence, 50139
Research Site
Padua, 35128
Research Site
Pisa, 56126
Research Site
Roma, 00168
Research Site
Rozzano, 20089
France6 sites
Research Site
Le Kremlin-Bicêtre, 94270
Research Site
Marseille, 13005
Research Site
Nantes, 44093
Research Site
Pierre-Bénite, 69495
Research Site
Poitiers, 86000
Research Site
Toulouse, 31400
Spain6 sites
Research Site
Barcelona, 08003
Research Site
Barcelona, 08035
Research Site
Cadiz, 11011
Research Site
Madrid, 28041
Research Site
Salamanca, 37007
Research Site
Santiago de Compostela, 15706
United States4 sites
Research Site
Chestnut Hill, Massachusetts, 02467
Research Site
Chicago, Illinois, 60611
Research Site
Columbia, Missouri, 65201
Research Site
Newport Beach, California, 92663
Germany4 sites
Research Site
Marburg, 35043
Research Site
Tübingen, 72076
Research Site
Villingen-Schwenningen, 78052
Research Site
Wiesbaden, 65183
Hungary4 sites
Research Site
Budapest, 1085
Research Site
Budapest, 1134
Research Site
Nyíregyháza, 4400
Research Site
Pécs, 7621
Poland4 sites
Research Site
Bialystok, 15-879
Research Site
Bydgoszcz, 85-231
Research Site
Lodz, 90-302
Research Site
Zawadzkie, 47-120
Bulgaria3 sites
Research Site
Plovdiv, 4003
Research Site
Sofia, 1431
Research Site
Sofia, 1606
Canada3 sites
Research Site
Hamilton, Ontario, L8S 1G5
Research Site
Québec, Quebec, G1L 3L5
Research Site
Québec, Quebec, G1V 4W2
About this study
Official title: A Multicentre, Single-Arm, Phase 3b Study to Assess Changes in Symptoms in Adult Participants With Chronic Rhinosinusitis With Nasal Polyposis Initiating Treatment With Tezepelumab (ESSENCE)
The main objective of this study is to evaluate treatment outcomes of tezepelumab among participants with physician-determined surgery-eligible CRSwNP, with or without asthma.
Study details include:
- The study duration will be up to 40 weeks.
- The treatment duration will be up to 24 weeks.
- The visit frequency will be once every 4 weeks (Q4W).
Read the detailed description
This is a multicentre, open-label, single-arm, phase IIIb study is to describe changes from baseline in (1) participant-reported nasal congestion as evaluated by the nasal congestion score (NCS) and (2) participant-reported sino-nasal symptoms as evaluated by sino-nasal outcome test, 22 item (SNOT-22) following initiation of tezepelumab treatment.
Approximately 60 sites in 10 countries will enrol adult patients with physician determined surgery eligible CRSwNP.
The study is divided into 3 periods as described below:
- Screening Period (from Week -4 until Week 0, up to 4 Weeks)
- Treatment period (Week 0 to Week 24)
- Safety Follow-up Period (Week 24 to Week 36)
- Conditions
- Chronic Rhinosinusitis With Nasal Polyps
- Being tested
- Tezepelumab
- Keywords
- Chronic rhinosinusitis, Rhinosinusitis
- Medical subject headings
- Rhinosinusitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TezepelumabCombination product
Also called TEZSPIRE®
IMP. Subcutaneous injection. Unit dose strengths 210 mg.
| Study group | Role | What they receive |
|---|---|---|
| Tezepelumab | Experimental | Tezepelumab: Tezepelumab single dose subcutaneously injection. Receives: Combination Product: Tezepelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in nasal congestion
Changes from baseline in participant-reported nasal congestion as evaluated by the nasal congestion score (NCS) as part of the nasal polyposis symptom diary (NPSD) following initiation of tezepelumab treatment.
Measured: Week 24
Change from baseline in sino-nasal symptoms
changes from baseline in participant reported sino nasal symptoms as evaluated by sino nasal outcome test, 22 item (SNOT 22) total score following initiation of tezepelumab treatment.
Measured: Week 24
Secondary outcomes (44)
Proportion of NCS responders
Proportion of NCS responders (minimal clinically important difference [MCID] from baseline = 1.0) at each collected timepoint.
Measured: End of treatment - Week 24
Time to first response for NCS
Description of time to first response for NCS by analysing data at all collected timepoints.
Measured: End of Treatment-week 24
Change from baseline in NCS
Change from baseline in NCS at each collected timepoint.
Measured: Daily for the 2 weeks prior to Week 0 through end of treatment visit (EOT; Week 24).
Proportion of SNOT-22 responders
Proportion of SNOT-22 responders (MCID from baseline = -8.9) at each collected timepoint.
Measured: Screening, Weeks 0, 2, 4, 8, 12, 16, 20, and 24.
Time to first response for SNOT-22
Description of time to first response for SNOT-22 by analysing data at all collected timepoints.
Measured: Screening, Weeks 0, 2, 4, 8, 12, 16, 20, and 24.
Change from baseline in SNOT-22
Change from baseline in SNOT-22 at each collected timepoint.
Measured: Screening, Weeks 0, 2, 4, 8, 12, 16, 20, and 24.
Change from baseline visit in nasal blockage (NB)
Change from baseline visit in NB measured by PNIF
Measured: Weeks 0, 4, 12, and 24.
Change from baseline visit in NB
Change from baseline visit in NB measured by VAS-NB
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, 24.
Proportion of PNIF responders
Proportion of PNIF responders (MCID from baseline =20 L/min).
Measured: Weeks 0, 4, 12, and 24.
Proportion of VAS-NB responders
Proportion of VAS-NB responders (MCID from baseline = -3.0) (in participants with VAS-NB ≥ 7 at baseline).
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, 24.
Time to first response for PNIF
Description of time to first response for PNIF by analysing data at all collected timepoints.
Measured: Weeks 0, 4, 12, and 24
First response for VAS NB
Description of time to first response for VAS NB by analysing data at all collected timepoints (in participants with VAS-NB ≥ 7 at baseline).
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, 24.
Change from baseline in loss of smell score evaluated by UPSIT or Sniffin Sticks
Change from baseline in loss of smell score evaluated by UPSIT or Sniffin Sticks
Measured: Weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24
Change from baseline in loss of smell score evaluated by VAS-Taste
Change from baseline in loss of smell score evaluated by VAS-Taste
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
Change from baseline in loss of smell score evaluated by VAS-Smell
Change from baseline in loss of smell score evaluated by VAS-Smell
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
Proportion of UPSIT responders
Proportion of UPSIT responders (MCID from baseline = 4)
Measured: Weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24.
Proportion of Sniffin sticks responders
Proportion of Sniffin sticks responders (MCID from baseline = 6)
Measured: Weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24
Proportion of VAS-Smell responders
Proportion of VAS-Smell responders (MCID from baseline = -3.0) (in participants with VAS-Smell ≥ 7 at baseline)
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
Proportion of participants with a reduction in VAS-Taste score from baseline
Proportion of participants with a reduction in VAS-Taste score from baseline (in participants with VAS-Taste ≥ 7 at baseline)
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
Time to first response for UPSIT/Sniffin sticks
Time to first response for UPSIT/Sniffin sticks by analysing data at all collected timepoints.
Measured: Weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24
Time to first response for VAS Smell
Time to first response for VAS Smell by analysing data at all collected timepoints (in participants with VAS-Smell ≥ 7 at baseline).
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
Time to first improvement in VAS-Taste
Time to first improvement in VAS-Taste by analysing data at all collected timepoints (in participants with VAS-Taste ≥ 7 at baseline).
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
Change from baseline in sleep as evaluated by PSQI total score
Change from baseline in sleep as evaluated by PSQI total score
Measured: Weeks 0, 12, and 24.
Change from baseline in sleep as evaluated by SNOT-22 Sleep domain score
Change from baseline in sleep as evaluated by SNOT-22 Sleep domain score
Measured: Screening, Week 0, Weeks 2, 4, 8, 12, 16, 20, and 24
Change from baseline in sleep as evaluated by VAS-Sleep
Change from baseline in sleep as evaluated by VAS-Sleep
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
Proportion of PSQI responders
Proportion of PSQI responders (MCID from baseline = - 4.4)
Measured: Weeks 0, 12, and 24
Proportion of SNOT-22 Sleep domain responders
Proportion of SNOT-22 Sleep domain responders (MCID from baseline = -2.9)
Measured: Screening, Week 0, Weeks 2, 4, 8, 12, 16, 20, and 24
Proportion of participants with any improvement in VAS Sleep from baseline
Proportion of participants with any improvement in VAS Sleep from baseline (in participants with VAS-Sleep ≥ 7 at baseline)
Measured: Daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
Time to first response for PSQI
Time to first response for PSQI by analysing data at all collected timepoints.
Measured: Weeks 0, 12, and 24.
Time to first response for SNOT-22 Sleep domain
Time to first response for SNOT-22 Sleep domain by analysing data at all collected timepoints.
Measured: Screening, Week 0, Weeks 2, 4, 8, 12, 16, 20, and 24.
Time to first improvement for VAS-Sleep
Time to first improvement for VAS-Sleep by analysing data at all collected timepoints (in participants with VAS-Sleep ≥ 7 at baseline).
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
Change from baseline in total NPS
Change from baseline in total NPS evaluated by nasal endoscopy.
Measured: Screening, Weeks 2 and 24
Proportion of NPS responders
Proportion of NPS responders (MCID from baseline = 1.0) at Weeks 2 and 24.
Measured: Screening, Weeks 2 and 24
Change from baseline in NPQ score
Change from baseline in NPQ score
Measured: Weeks 0, 8, 12, and 24.
Proportion of NPQ responders
Proportion of NPQ responders (MCID from baseline = 7.0)
Measured: Weeks 0, 8, 12, and 24
Time to first response for NPQ
Time to first response for NPQ by analysing data collected at each specified timepoint.
Measured: Weeks 0, 8, 12, and 24.
Change from baseline in TSS
Change from baseline in TSS
Measured: daily for the 2 weeks prior to Week 0 and through EOT (Week 24)
Proportion of TSS responders
Proportion of TSS responders (MCID from baseline = 4.0)
Measured: daily for the 2 weeks prior to Week 0 and through EOT (Week 24)
Time to first response for TSS
Time to first response for TSS by analysing data at all collected timepoints.
Measured: daily for the 2 weeks prior to Week 0 and through EOT (Week 24)
Change from baseline in NP severity
Change from baseline in NP severity as measured by VAS Overall symptoms
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
Proportion of VAS Overall symptom responders
Proportion of VAS Overall symptom responders (MCID from baseline = 2.5)
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
Time to first response for VAS-Overall symptom
Time to first response for VAS-Overall symptom by analysing data at all collected timepoints
Measured: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
Proportion of participants who respond as 'well controlled' or 'completely controlled' NP symptoms to the NP control question
Proportion of participants who respond as 'well controlled' or 'completely controlled' NP symptoms to the NP control question
Measured: Weeks 0, 4, 8, 12, 20, and 24.
Time to first response for NP control
Time to first response for NP control by analysing data at all collected timepoints.
Measured: Weeks 0, 4, 8, 12, 20, and 24.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2024
- Study start3 Dec 2024
- Primary completion13 Jan 2027 (estimated)
- Study completion13 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Rhinosinusitis With Nasal PolypsStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-Label, single-arm treatment study. Participants will be treated with tezepelumab Q4W from Week 0, with the last dose administered at Week 20
- Masking
- None (open label)
- Enrolment
- 181 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Fortrea
- Responsible party
- Sponsor
- Investigators
- Tanya M Laidlaw, MD, Principal investigator, Director of Translational Research in Allergy and Director of the Aspirin-Exacerbated Respiratory Disease (AERD) Centre at the Brigham and Women's Hospital.Enrico Heffler, MD, PhD, Principal investigator, Associate Professor of Internal Medicine and Consultant at the Personalized Medicine, Asthma and Allergy Unit at IRCCS Humanitas Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06706817
- Sponsor's protocol ID
- D5242C00002
- Acronym
- ESSENCE
- Status last verified
- Oct 2026
- First submitted
- 7 Nov 2024
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests 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 approved.