TEZEPELUMAB for Chronic rhinosinusitis with nasal polyps

Inclusion criteria

• {"criterion_text":"- Participants must be 18 years of age or older, at the time of signing the informed consent."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Body weight of ≥ 40 kg at Visit 1"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Provision of signed and dated written ICF as described in Appendix A 3 prior to any mandatory study-specific procedures, sampling, and analyses."}
• {"criterion_text":"- 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

• {"criterion_text":"- Participants with documented allergic fungal rhinosinusitis and/or central compartment atopic disease."}
• {"criterion_text":"- History of chronic alcohol or drug abuse within 12 months prior to Visit 1."}
• {"criterion_text":"- Tuberculosis requiring treatment within the 12 months prior to Visit 1."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Receipt of immunoglobulin or blood products within 30 days prior to Visit 1."}
• {"criterion_text":"- Receipt of live attenuated vaccines 30 days prior to the date of Visit 1 and during the study including the follow-up period."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Receipt of COVID-19 vaccine (regardless of vaccine delivery platform) within 28 days prior to date of first tezepelumab administration at Visit 2."}
• {"criterion_text":"- Known history of sensitivity to any component of the tezepelumab formulation or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation."}
• {"criterion_text":"- History of anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy."}
• {"criterion_text":"- Regular use of decongestants (topical or systemic) from Visit 1 onward is not allowed unless used for endoscopic procedure."}
• {"criterion_text":"- Use of corticosteroid-eluting intranasal stents within 6 months prior to Visit 1 and during the study period."}
• {"criterion_text":"- Recent aspirin desensitization within 6 months of enrolment."}
• {"criterion_text":"- Concurrent enrolment in another clinical study involving an IMP."}
• {"criterion_text":"- Any clinically meaningful abnormal finding in physical examination, haematology, or clinical chemistry at Visit 1 which, in the opinion of the investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study."}
• {"criterion_text":"- Evidence of active liver disease, including jaundice or AST, ALT, or ALP > 2 times ULN at Visit 1."}
• {"criterion_text":"- Positive hepatitis B surface antigen, or hepatitis C antibody serology at screening, or a positive medical history for hepatitis B or C. Participants with a history of hepatitis B vaccination without a history of hepatitis B are allowed to participate."}
• {"criterion_text":"- 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: •\tAffect the safety of the participant throughout the study •\tInfluence the findings of the study or the interpretation •\tImpede the participant's ability to complete the entire duration of study."}
• {"criterion_text":"- Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff), or participants employed by or relatives of the employees of the site or sponsor."}
• {"criterion_text":"- Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements."}
• {"criterion_text":"- For women only: Pregnant, breastfeeding, or lactating women. A serum β-HCG pregnancy test must be drawn for WOCBP at the screening visit. If the results of the serum β-HCG cannot be obtained prior to dosing of the IMP, a participant may be enrolled on the basis of a negative urine pregnancy test, though serum β-HCG must still be obtained. If either test is positive, the participant should be excluded. Since urine and serum tests may miss a pregnancy in the first days after conception, relevant menstrual history and sexual history, including methods of contraception, should be considered. Any participant whose menstrual and/or sexual history suggests the possibility of early pregnancy should be excluded."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- History of cancer: (a)\tParticipants 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. (b)\tParticipants who have had other malignancies are eligible provided that curative therapy was completed at least 5 years prior to Visit 1."}
• {"criterion_text":"- Uncontrolled epistaxis within 2 months of Visit 1"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- Change from baseline in nasal congestion measured by the NCS at Week 24.","definition_or_measurement_approach":"Measured by the nasal congestion score (NCS); change from baseline evaluated at Week 24."}
• {"endpoint_text":"- Change from baseline in sino-nasal symptoms measured by SNOT-22 total score at Week 24.","definition_or_measurement_approach":"Measured by the Sino-Nasal Outcome Test 22-item (SNOT-22) total score; change from baseline evaluated at Week 24."}

Secondary endpoints

• {"endpoint_text":"- Proportion of NCS responders (minimal clinically important difference [MCID] from baseline = 1.0) at each collected timepoint. •\tDescription of time to first response for NCS by analysing data at all collected timepoints. •\tChange from baseline in NCS at each collected timepoint.","definition_or_measurement_approach":"Responder defined as MCID from baseline = 1.0; analyses include responder proportion at each timepoint, time-to-first-response across collected timepoints, and change-from-baseline in NCS at each timepoint."}
• {"endpoint_text":"- Proportion of SNOT-22 responders (MCID from baseline = -8.9) at each collected timepoint. •\tDescription of time to first response for SNOT-22 by analysing data at all collected timepoints. •\tChange from baseline in SNOT-22 at each collected timepoint.","definition_or_measurement_approach":"Responder defined as MCID from baseline = -8.9; analyses include responder proportion at each timepoint, time-to-first-response, and change-from-baseline in SNOT-22 at each timepoint."}
• {"endpoint_text":"- Change from baseline visit in NB measured by: 1. PNIF 2. VAS-NB 3. Proportion of PNIF, VAS-NB responders, 4. Description of time to first response for PNIF, VAS NB","definition_or_measurement_approach":"Nasal blockage (NB) measured by Peak Nasal Inspiratory Flow (PNIF) and visual analogue scale for nasal blockage (VAS-NB); responder proportions and time-to-first-response analysed for PNIF and VAS-NB."}
• {"endpoint_text":"- Change from baseline in loss of smell score evaluated by: 1. UPSIT or Sniffin Sticks 2. VAS-Taste 3. VAS-Smell 4. Proportion of UPSIT, Sniffin sticks, VAS-Smell responders 5. Proportion of participants with a reduction in VAS-Taste score from baseline 6. Description of time to first response for UPSIT/Sniffin sticks, VAS Smell , improvement in VAS-Taste","definition_or_measurement_approach":"Sense of smell/taste evaluated by UPSIT or Sniffin Sticks, VAS-Smell and VAS-Taste; analyses include change-from-baseline, responder proportions, and time-to-first-response."}
• {"endpoint_text":"- Change from baseline in sleep as evaluated by: 1. PSQI total score 2. SNOT-22 Sleep domain score 3. VAS-Sleep 4. Proportion of PSQI, SNOT-22 Sleep domain responders 5. Proportion of participants with any improvement in VAS Sleep from baseline 6. Description of time to first response for PSQI, SNOT-22 Sleep domain, improvement for VAS-Sleep","definition_or_measurement_approach":"Sleep evaluated by Pittsburgh Sleep Quality Index (PSQI) total score, SNOT-22 sleep domain, and VAS-Sleep; endpoints include change-from-baseline, responder proportions, and time-to-first-response."}
• {"endpoint_text":"- Change from baseline in total NPS evaluated by nasal endoscopy. Summary measures: mean (SD) and distribution of NPS as assessed by above measures will be described at each visit. Other analysis: Proportion of responders 2.\tProportion of NPS responders (MCID from baseline = 1.0) at Weeks 2 and 24.","definition_or_measurement_approach":"Nasal polyp score (NPS) assessed by nasal endoscopy; summary measures (mean, SD, distribution) by visit; responder defined as MCID = 1.0 at Weeks 2 and 24."}
• {"endpoint_text":"- Change from baseline in NPQ score Summary measures: mean (SD) and distribution of NPQ scores will be described. Other analyses 3.\tProportion of NPQ responders (MCID from baseline = 7.0) 4.\tDescription of time to first response for NPQ by analysing data collected at each specified timepoint.","definition_or_measurement_approach":"Nasal Polyposis Quality of Life (NPQ) score change-from-baseline with summary measures; responder defined as MCID = 7.0; time-to-first-response analysed."}
• {"endpoint_text":"- Change from baseline in TSS Summary measures: mean (SD) and distribution of TSS will be described. Other analyses 3.\tProportion of TSS responders (MCID from baseline = 4.0) 4.\tDescription of time to first response for TSS by analysing data at all collected timepoints.","definition_or_measurement_approach":"Total Nasal Symptom Score (TSS) change-from-baseline with summary measures; responder defined as MCID = 4.0; time-to-first-response analysed."}
• {"endpoint_text":"- Change from baseline in NP severity as measured by VAS Overall symptoms 3.\tProportion of VAS Overall symptom responders (MCID from baseline = 2.5) 4.\tDescription of time to first response for VAS-Overall symptom by analysing data at all collected timepoints","definition_or_measurement_approach":"Overall NP severity measured by VAS Overall symptoms; responder defined as MCID = 2.5; includes change-from-baseline, responder proportion and time-to-first-response."}
• {"endpoint_text":"- Proportion of participants who respond as ‘well controlled’ or ‘completely controlled’ NP symptoms to the NP control question Other analysis: time to first response •\tDescription of time to first response for NP control by analysing data at all collected timepoints.","definition_or_measurement_approach":"Participant-reported NP control question categorised as 'well controlled' or 'completely controlled'; analyses include proportion and time-to-first-response across timepoints."}

Methods

• Site-based recruitment using K1 recruitment and informed consent procedures (documents present: K1_Recruitment and Informed Consent Procedure Form).
• Use of K2 recruitment materials (patient brochure and poster) at sites (country-/language-specific recruitment materials available).
• Distribution of printed recruitment brochures/posters and patient brochures at investigational sites and via site contacts (materials provided in multiple language versions per country).
• Provision of patient reimbursement support (Scarritt Group Inc. listed with duty 'Patient Reimbursement').
• Use of third-party patient information/education support (Center For Information And Study On Clinical Research Participation Inc. listed among third parties).

Hungary

Earliest CTIS Part Ii Submission Date

31-01-2025

Latest Decision Or Authorization Date

26-02-2025

Processing Time Days

26

Number Of Sites

4

Number Of Participants

50

Poland

Earliest CTIS Part Ii Submission Date

11-02-2025

Latest Decision Or Authorization Date

02-03-2025

Processing Time Days

19

Number Of Sites

4

Number Of Participants

26

Bulgaria

Earliest CTIS Part Ii Submission Date

03-02-2025

Latest Decision Or Authorization Date

12-06-2025

Processing Time Days

129

Number Of Sites

4

Number Of Participants

50

France

Earliest CTIS Part Ii Submission Date

08-01-2025

Latest Decision Or Authorization Date

18-08-2025

Processing Time Days

222

Number Of Sites

8

Number Of Participants

50

Italy

Earliest CTIS Part Ii Submission Date

06-01-2025

Latest Decision Or Authorization Date

23-12-2025

Processing Time Days

351

Number Of Sites

8

Number Of Participants

70

Spain

Earliest CTIS Part Ii Submission Date

03-02-2025

Latest Decision Or Authorization Date

19-04-2026

Processing Time Days

440

Number Of Sites

7

Number Of Participants

60

Germany

Earliest CTIS Part Ii Submission Date

09-12-2024

Latest Decision Or Authorization Date

19-04-2026

Processing Time Days

496

Number Of Sites

5

Number Of Participants

50

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Fortrea Inc.

Responsibilities

codes: 1,10,11,12,13,2,5,6,7,8,9

Name

Medidata Solutions Inc.

Responsibilities

EDC, eCOA,

Name

Perceptive Eclinical Limited

Responsibilities

code: 3

Name

Labcorp Central Laboratory Services SARL

Responsibilities

code: 4

Third parties

• {"country":"United States","full_name":"Myonex LLC","duties_or_roles":"Sniffing Sticks/ UPSIT","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Center For Information And Study On Clinical Research Participation Inc.","duties_or_roles":"Center For Information And Study On Clinical Research Participation Inc. (CISCRP)","organisation_type":"Patient organisation/association"}
• {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"code: 3","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"Translations & Licensing of PROs","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"code: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Welocalize Inc.","duties_or_roles":"Translation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"EDC, eCOA,","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"codes: 1,10,11,12,13,2,5,6,7,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scarritt Group Inc.","duties_or_roles":"Patient Reimbursement","organisation_type":"Non-Pharmaceutical company"}