RECRUITING

A Study to Investigate Changes in Symptoms in Adult Participants With Chronic Rhinosinusitis With Nasal Polyposis Initiating Treatment With Tezepelumab

Conditions

Chronic Rhinosinusitis With Nasal Polyps Chronic rhinosinusitis Rhinosinusitis

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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. The visit frequency will be once every 4 weeks (Q4W).

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)

Quick Facts

Study Start:2024-12-03

Study Completion:2027-01-26

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06706817

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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. * 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. * 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.	* 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. * 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: 1. 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. 2. 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.

Inclusion Criteria

Exclusion Criteria

* 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.
* 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.
* 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.

* 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.
* 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:
1. 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.
2. 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.

Contacts and Locations

Study Contact

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479

information.center@astrazeneca.com

Principal Investigator

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

Study Locations (Sites)

Research Site

Newport Beach, California, 92663

United States

Research Site

Chicago, Illinois, 60611

United States

Research Site

Chestnut Hill, Massachusetts, 02467

United States

Research Site

Columbia, Missouri, 65201

United States

Collaborators and Investigators

Sponsor: AstraZeneca

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

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-03

Study Completion Date2027-01-26

Study Record Updates

Study Start Date2024-12-03

Study Completion Date2027-01-26

Terms related to this study

Keywords Provided by Researchers

Chronic rhinosinusitis
Rhinosinusitis

Additional Relevant MeSH Terms

Chronic Rhinosinusitis With Nasal Polyps