Efficacy and safety of tezepelumab in participants with Severe Chronic Rhinosinusitis with Nasal Polyposis

Phase 1

• Conditions: Severe Chronic Rhinosinusitis with Nasal Polyposis; MedDRA version: 20.1Level: PTClassification code 10080060Term: Chronic rhinosinusitis with nasal polypsSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2020-003062-39-HU
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-12-09
• Last Update Posted: 8 January 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Participants with physician-diagnosed CRSwNP for at least 12 months prior to Visit 1 that have:
a. Severity consistent with need for surgery as defined by total NPS = 5 (= 2 for each nostril) at screening, as determined by the central reader
b. Nasal Congestion Score (NCS) = 2 at Visit 1
c. Ongoing documented NP symptoms over > 8 weeks prior to screening such as rhinorrhea and/or reduction/loss of smell

2. SNOT-22 total score = 30 at screening (Visit 1)

3. Any standard of care for treatment of CRSwNP provided the participant is stable on that treatment for 30 days prior to Visit 1

4. Documented treatment of nasal polyposis 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 and/or any history of NP surgery (or contraindications/intolerance to)

Additional criteria to be checked prior to randomisation (Visit 3)

1. Confirmed central reading total NPS = 5 (= 2 for each nostril) at Visit 2

2. Bi-weekly mean NCS= 2 (baseline bi-weekly mean score collected from study Day -13 to study Day 0)

3. SNOT-22 score = 30 at randomisation (Visit 3)

4. At least 8 days of evaluable daily diary data in the 14-day period prior to randomisation (baseline bi-weekly mean score collected from study Day – 13 to study Day 0)

5. Subjects must have demonstrated a minimum 70% compliance with diary completion during the screening and run-in periods from Visit 1 to Visit 3.

6. At least 70% compliance with the participant’s background INCS as captured in the eDiary during the screening and run-in periods from Visit 1 to Visit 3.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1. Any clinically important comorbidities other than asthma (e.g. active lung infection, bronchiectasis, pulmonary fibrosis, cystic fibrosis, primary ciliary dyskinesia, allergic bronchopulmonary mycosis, hypereosinophilic syndromes, etc.) that could confound interpretation of clinical efficacy results.

2. 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.

3. Positive COVID-19 PCR test (or COVID-19 rapid test) or COVID-19 entry screening questionnaire during the screening visit. In case of long turnaround time of the nasopharyngeal swab test results from central lab, the site has the following alternatives:
- Perform COVID-19 nasopharyngeal or oropharyngeal swab test through local lab
- Perform a COVID-19 rapid antigen test at the site, provided it is approved by the local health authorities.

4. Regular use of decongestants (topical or systemic) at enrolment is not allowed unless used for endoscopic procedure.

5. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine, hydroxychloroquine, systemic corticosteroids for condition or any experimental anti-inflammatory therapy) within 3 months prior to Visit 1 and during the study period. Systemic corticosteroid use is defined as treatment with a burst of systemic corticosteroids for at least 3 consecutive days or a single IM depo-injectable dose of corticosteroids (considered equivalent to a 3-day burst of systemic corticosteroids)

6. Receipt of COVID-19 vaccine (regardless of vaccine delivery platform) 28 days prior to date of IP administration at V3 (randomisation visit).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified