Clinical trial NCT06706817: A Study to Investigate Changes in Symptoms in Adult Participants With Chronic Rhinosinusitis With Nasal Polyposis Initiating Treatment With Tezepelumab
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Keywords: Chronic rhinosinusitis
Rhinosinusitis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Fortrea
First posted: 2024-11-27
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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
Primary purpose: TREATMENT

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

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)

Eligibility criteria: Inclusion 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.

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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change from baseline in nasal congestion
timeFrame: Week 24
measure: Change from baseline in sino-nasal symptoms
timeFrame: Week 24
Secondary outcomes:
measure: Proportion of NCS responders
timeFrame: End of treatment - Week 24
measure: Time to first response for NCS
timeFrame: End of Treatment-week 24
measure: Change from baseline in NCS
timeFrame: Daily for the 2 weeks prior to Week 0 through end of treatment visit (EOT; Week 24).
measure: Proportion of SNOT-22 responders
timeFrame: Screening, Weeks 0, 2, 4, 8, 12, 16, 20, and 24.
measure: Time to first response for SNOT-22
timeFrame: Screening, Weeks 0, 2, 4, 8, 12, 16, 20, and 24.
measure: Change from baseline in SNOT-22
timeFrame: Screening, Weeks 0, 2, 4, 8, 12, 16, 20, and 24.
measure: Change from baseline visit in nasal blockage (NB)
timeFrame: Weeks 0, 4, 12, and 24.
measure: Change from baseline visit in NB
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, 24.
measure: Proportion of PNIF responders
timeFrame: Weeks 0, 4, 12, and 24.
measure: Proportion of VAS-NB responders
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, 24.
measure: Time to first response for PNIF
timeFrame: Weeks 0, 4, 12, and 24
measure: First response for VAS NB
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, 24.
measure: Change from baseline in loss of smell score evaluated by UPSIT or Sniffin Sticks
timeFrame: Weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24
measure: Change from baseline in loss of smell score evaluated by VAS-Taste
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
measure: Change from baseline in loss of smell score evaluated by VAS-Smell
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
measure: Proportion of UPSIT responders
timeFrame: Weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24.
measure: Proportion of Sniffin sticks responders
timeFrame: Weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24
measure: Proportion of VAS-Smell responders
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
measure: Proportion of participants with a reduction in VAS-Taste score from baseline
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
measure: Time to first response for UPSIT/Sniffin sticks
timeFrame: Weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24
measure: Time to first response for VAS Smell
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
measure: Time to first improvement in VAS-Taste
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
measure: Change from baseline in sleep as evaluated by PSQI total score
timeFrame: Weeks 0, 12, and 24.
measure: Change from baseline in sleep as evaluated by SNOT-22 Sleep domain score
timeFrame: Screening, Week 0, Weeks 2, 4, 8, 12, 16, 20, and 24
measure: Change from baseline in sleep as evaluated by VAS-Sleep
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
measure: Proportion of PSQI responders
timeFrame: Weeks 0, 12, and 24
measure: Proportion of SNOT-22 Sleep domain responders
timeFrame: Screening, Week 0, Weeks 2, 4, 8, 12, 16, 20, and 24
measure: Proportion of participants with any improvement in VAS Sleep from baseline
timeFrame: Daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
measure: Time to first response for PSQI
timeFrame: Weeks 0, 12, and 24.
measure: Time to first response for SNOT-22 Sleep domain
timeFrame: Screening, Week 0, Weeks 2, 4, 8, 12, 16, 20, and 24.
measure: Time to first improvement for VAS-Sleep
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24
measure: Change from baseline in total NPS
timeFrame: Screening, Weeks 2 and 24
measure: Proportion of NPS responders
timeFrame: Screening, Weeks 2 and 24
measure: Change from baseline in NPQ score
timeFrame: Weeks 0, 8, 12, and 24.
measure: Proportion of NPQ responders
timeFrame: Weeks 0, 8, 12, and 24
measure: Time to first response for NPQ
timeFrame: Weeks 0, 8, 12, and 24.
measure: Change from baseline in TSS
timeFrame: daily for the 2 weeks prior to Week 0 and through EOT (Week 24)
measure: Proportion of TSS responders
timeFrame: daily for the 2 weeks prior to Week 0 and through EOT (Week 24)
measure: Time to first response for TSS
timeFrame: daily for the 2 weeks prior to Week 0 and through EOT (Week 24)
measure: Change from baseline in NP severity
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
measure: Proportion of VAS Overall symptom responders
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
measure: Time to first response for VAS-Overall symptom
timeFrame: daily for the 2 weeks prior to Week 0 through the first 12 weeks of Treatment Period, and at Weeks 16, 20, and 24.
measure: Proportion of participants who respond as 'well controlled' or 'completely controlled' NP symptoms to the NP control question
timeFrame: Weeks 0, 4, 8, 12, 20, and 24.
measure: Time to first response for NP control
timeFrame: Weeks 0, 4, 8, 12, 20, and 24.
Other outcomes:
measure: Endoscopy findings will be used to describe histological changes and describe CRSwNP visualization
timeFrame: Screening, Weeks 2 and 24
measure: Change from baseline in blood eosinophil count (BEC), total serum IgE, specific IgE (including fungi/moulds [eg, Alternaria]), S. aureus enterotoxin IgE, and Fractional exhaled nitric oxide (FeNO; for asthma participants only)
timeFrame: Screening (for BEC and FeNO), Week 0 (for IgE and S. aureus enterotoxin IgE), Weeks 12 and 24
measure: Change from baseline in WPAI-CRSwNP
timeFrame: Week 0 and Week 24
measure: Proportion and annualised rate of primary care visits (all rates for CRSwNP-related and asthma-related).
timeFrame: 24 weeks pre-and post index (index = 1st tezepelumab dosing).
measure: Change in incident rate of nasal infection comparing the post-index period versus the pre-index period
timeFrame: 24 weeks pre- and post-index. (index = 1st tezepelumab dosing)
measure: Change in proportion of participants with CRSwNP-related SCS use during the post-index period (24 weeks following tezepelumab first dose) versus the pre-treatment period (24 weeks prior to tezepelumab first dose)
timeFrame: 24-weeks pre- and post- index. (index = 1st tezepelumab dosing).
measure: Change in average SCS daily dose during the post-index period versus dose at/closest to the index
timeFrame: 24-weeks pre- and post- index. (index = 1st tezepelumab dosing).
measure: Proportion of participants with the decision for CRSwNP surgery during the 24 weeks pre- and post-index and change in NP surgery proportion following tezepelumab initiation.
timeFrame: 24-weeks pre- and post- index. (index = 1st tezepelumab dosing).
measure: Proportion of patients with CRSwNP exacerbation
timeFrame: 24-weeks pre- and post-index (index = 1st tezepelumab dosing).
measure: Change since baseline in Asthma Control Questionnaire 6 (ACQ-6) score
timeFrame: Weeks 0 and 24.
measure: ACQ-6 responder: proportion of participants with change since baseline in ACQ-6 of 0.5 or above
timeFrame: Weeks 0 and 24
measure: Annualised asthma exacerbation rate
timeFrame: 24 weeks pre-and post-index (index = 1st tezepelumab dosing).
measure: Change from baseline in Annualised asthma exacerbation rate
timeFrame: 24 weeks pre-and post-index (index = 1st tezepelumab dosing).
measure: Lung function (Forced expiratory volume in 1 second [FEV1]) (if available at site)
timeFrame: Weeks 0, 12 (lung function only) and 24.
measure: Asthma-related SCS use (yes/no)
timeFrame: 24 weeks pre-and post-index (index = 1st tezepelumab dosing).
measure: Proportion and annualised rate of urgent care (all rates for CRSwNP-related and asthma-related).
timeFrame: 24 weeks pre-and post index (index=1st tezepelumab dosing)
measure: Proportion and annualised rate of unplanned surgery (all rates for CRSwNP-related and asthma-related).
timeFrame: 24 weeks pre and post index (index=ist tezepelumab dosing)
measure: Proportion and annualised rate of unplanned out participant visits (all rates for CRSwNP-related and asthma-related).
timeFrame: 24 weeks pre- and post index (index=1st tezepelumab dosing)
measure: Proportion and annualised rate of emergency room visits (all rates for CRSwNP-related and asthma-related).
timeFrame: 24 weeks pre-and post index (index=1st tezepelumab dosing)
measure: Proportion and annualised rate of hospitalisations (all rates for CRSwNP-related and asthma-related).
timeFrame: 24 weeks pre-and post index(index=1st tezepelumab dosing)
measure: Asthma related SCS use as part of an exacerbation
timeFrame: 24 weeks pre-and post index(index=1st tezepelumab dosing)
measure: Asthma related SCS duration of use
timeFrame: 24 weeks pre-and post index(index=1st tezepelumab dosing)
measure: Asthma related SCS daily dose
timeFrame: 24 weeks pre-and post index(index=1st tezepelumab dosing)
Locations:
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Chestnut Hill
country: United States
facility: Research Site
state: Massachusetts
city: Columbia
country: United States
facility: Research Site
state: Missouri
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Quebec
country: Canada
facility: Research Site
city: Quebec
country: Canada
facility: Research Site
city: Le Kremlin Bicêtre
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Pierre Benite
country: France
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
facility: Research Site
city: Düsseldorf
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: Tubingen
country: Germany
facility: Research Site
city: Villingen-Schwenningen
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Nyiregyhaza
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Padua
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Zawadzkie
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Cadiz
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
Study officials:
affiliation: Director of Translational Research in Allergy and Director of the Aspirin-Exacerbated Respiratory Disease (AERD) Centre at the Brigham and Women's Hospital.
name: Tanya M Laidlaw, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Associate Professor of Internal Medicine and Consultant at the Personalized Medicine, Asthma and Allergy Unit at IRCCS Humanitas Research Hospital
name: Enrico Heffler, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: