A study to investigate changes in symptoms in adult participants with chronic rhinosinusitis with nasal polyposis initiating treatment with tezepelumab.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

26 Mar 2025 → ongoing

Decision date (initial)

2025-02-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB, Sweden

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

1. To describe 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.
2. To describe 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.

Secondary objectives 10

1. To describe responder proportion and time to response in participant-reported nasal congestion as evaluated by the nasal congestion score (NCS) following initiation of tezepelumab treatment.
2. To describe responder proportion and time to response in sino‑nasal symptoms as evaluated by sino‑nasal outcome test, 22 item (SNOT‑22) total score following initiation of tezepelumab treatment.
3. To describe changes in nasal blockage (NB) as evaluated by peak nasal inspiratory flow (PNIF) and by a visual analogue scale (VAS-NB) following initiation of tezepelumab treatment.
4. To describe changes in sense of smell/taste as evaluated by University of Pennsylvania Smell Identification Test (UPSIT) or Sniffin Stick, VAS-Smell and VAS-Taste following initiation of tezepelumab treatment.
5. To describe changes in sleep as evaluated by the Pittsburgh sleep quality index (PSQI), SNOT-22 Sleep domain, and VAS-Sleep following initiation of tezepelumab treatment.
6. To describe changes in nasal polyp score (NPS) following initiation of tezepelumab treatment.
7. To describe changes in NP quality of life (QoL) as evaluated by Nasal Polyposis Quality of Life (NPQ) following initiation of tezepelumab treatment.
8. To describe changes in overall symptoms as evaluated by NPSD Total Nasal Symptom Score (TSS) following initiation of tezepelumab treatment.
9. To describe changes in NP severity following initiation of tezepelumab treatment.
10. To describe responder proportion for NP control following initiation of tezepelumab treatment.

Conditions and MedDRA coding

Chronic Rhinosinusitis with Nasal Polyposis

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participants must be 18 years of age or older, at the time of signing the informed consent.
2. 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.
3. 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.
4. 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)
5. Body weight of ≥ 40 kg at Visit 1
6. 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.
7. Provision of signed and dated written ICF as described in Appendix A 3 prior to any mandatory study-specific procedures, sampling, and analyses.
8. 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 32

1. Participants with documented allergic fungal rhinosinusitis and/or central compartment atopic disease.
2. 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.
3. 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.
4. 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.
5. 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
6. History of cancer: (a) 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. (b) Participants who have had other malignancies are eligible provided that curative therapy was completed at least 5 years prior to Visit 1.
7. Uncontrolled epistaxis within 2 months of Visit 1
8. 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.
9. 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.
10. History of chronic alcohol or drug abuse within 12 months prior to Visit 1.
11. Tuberculosis requiring treatment within the 12 months prior to Visit 1.
12. 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.
13. 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.
14. 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.
15. 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).
16. 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.
17. 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.
18. Receipt of immunoglobulin or blood products within 30 days prior to Visit 1.
19. Receipt of live attenuated vaccines 30 days prior to the date of Visit 1 and during the study including the follow-up period.
20. Receipt of COVID-19 vaccine (regardless of vaccine delivery platform) within 28 days prior to date of first tezepelumab administration at Visit 2.
21. 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.
22. History of anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy.
23. Regular use of decongestants (topical or systemic) from Visit 1 onward is not allowed unless used for endoscopic procedure.
24. Use of corticosteroid-eluting intranasal stents within 6 months prior to Visit 1 and during the study period.
25. Recent aspirin desensitization within 6 months of enrolment.
26. Concurrent enrolment in another clinical study involving an IMP.
27. 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.
28. Evidence of active liver disease, including jaundice or AST, ALT, or ALP > 2 times ULN at Visit 1.
29. 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.
30. 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.
31. 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.
32. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change from baseline in nasal congestion measured by the NCS at Week 24.
2. Change from baseline in sino-nasal symptoms measured by SNOT-22 total score at Week 24.

Secondary endpoints 10

1. Proportion of NCS responders (minimal clinically important difference [MCID] from baseline = 1.0) at each collected timepoint. • Description of time to first response for NCS by analysing data at all collected timepoints. • Change from baseline in NCS at each collected timepoint.
2. Proportion of SNOT-22 responders (MCID from baseline = -8.9) at each collected timepoint. • Description of time to first response for SNOT-22 by analysing data at all collected timepoints. • Change from baseline in SNOT-22 at each collected timepoint.
3. 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
4. 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
5. 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
6. 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. Proportion of NPS responders (MCID from baseline = 1.0) at Weeks 2 and 24.
7. Change from baseline in NPQ score Summary measures: mean (SD) and distribution of NPQ scores will be described. Other analyses 3. Proportion of NPQ responders (MCID from baseline = 7.0) 4. Description of time to first response for NPQ by analysing data collected at each specified timepoint.
8. Change from baseline in TSS Summary measures: mean (SD) and distribution of TSS will be described. Other analyses 3. Proportion of TSS responders (MCID from baseline = 4.0) 4. Description of time to first response for TSS by analysing data at all collected timepoints.
9. Change from baseline in NP severity as measured by VAS Overall symptoms 3. Proportion of VAS Overall symptom responders (MCID from baseline = 2.5) 4. Description of time to first response for VAS-Overall symptom by analysing data at all collected timepoints
10. Proportion of participants who respond as ‘well controlled’ or ‘completely controlled’ NP symptoms to the NP control question Other analysis: time to first response • Description of time to first response for NP control by analysing data at all collected timepoints.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 10

Locations

7 EU/EEA countries · 38 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 132 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications