Nasal polyposis MedDRA version: 20.0 Level: LLT Classification code 10028754 Term: Nasal polyp System Organ Class: 100000004855
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Participants with bilateral sinonasal polyposis, and prior use of SCS (unless a medical contraindication) and ESS within 3 years, who have severity consistent with a need for surgery as described by: (a) A minimum total NPS of 4 out of a maximum score of 8 (with a unilateral score of at least 1 for each nostril) at V1 as determined by the study imaging core lab, (b) Ongoing symptoms for at least 12 weeks prior to V1 (question 11 of NPSQ); (c) Sinonasal symptom (SNOT-22) total score = 30 at enrolment (V1) Participant must meet the following criteria at the randomisation visit (V3): - Completion of surgical procedures consistent with those described in the Pre randomisation Surgical Guideline - Successful surgical polyp removal as evidenced by no visible polyps, confirmed by the Investigator - SNOT-22 improvement greater than or equal to the MCID of 8.9 compared to the assessment prior to surgery 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 175 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: - Participants with conditions or concomitant disease that makes them non-evaluable for the efficacy endpoint such as: (a) Unilateral antrochoanal polyps (b) Nasal septal deviation that occludes at least one nostril so as to prevent NPS scoring (c) Current rhinitis medicamentosa (d) Allergic fungal rhinosinusitis or allergic fungal sinusitis (e) Nasal cavity tumours - Clinically important comorbidities that could confound interpretation of clinical efficacy results including, but not limited to: active upper or lower respiratory tract infection, cystic fibrosis, primary ciliary dyskinesia, eosinophilic diseases other than asthma (eg, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic granulomatosis with polyangitis [Churg-Strauss syndrome], hypereosinophilic syndromes), granulomatosis with polyangitis (Wegener's granulomatosis), Young’s syndrome, etc. - Participants experiencing an asthma exacerbation requiring systemic (oral and/or parenteral) corticosteroids treatment or hospitalisation (> 24 hrs) for treatment of asthma within 4 weeks prior to V1. - Participants should not be randomised in case of persistent or new post-surgical infection (eg, fever or nasal muco-purulent discharge), uncontrolled pain, acute sinusitis, nasal infection, or upper respiratory infection in the 2 weeks before randomisation - History of anaphylaxis to any biologic therapy or vaccine. - A helminth parasitic infection diagnosed within 24 weeks prior to the date of informed consent and has not been treated with, or has failed to respond to standard of care therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of benralizumab vs placebo on the post-surgical recurrence of nasal polyps associated with worsening in CRSwNP (chronic rhinosinusitis with nasal polyposis) health status and/or clinical intervention;Secondary Objective: To evaluate the effect of benralizumab vs placebo on: - the post-surgical recurrence of nasal polyps - CRSwNP (chronic rhinosinusitis with nasal polyposis) health status associated with post-surgical recurrence of nasal polyps - changes in clinical interventions associated with post-surgical recurrence of nasal polyps - SCS use for relief of NP symptoms and/or the need for additional surgery - Nasal polyposis-associated symptoms - sense of smell - general HRQoL (Health-related quality of life) - sinus opacification (Lund-Mackay Score) Safety objectives: - To assess the safety and tolerability of benralizumab - To assess the pharmacokinetics and immunogenicity of benralizumab;Primary end point(s): Time from randomisation to the earliest recurrence of nasal polyps associated with SNOT-22 worsening and/or a clinical intervention. - Recurrence of nasal polyps will be determined by an NPS showing an increase = 1 from that recorded at baseline - SNOT-22 worsening is defined as a clinically meaningful deterioration in SNOT-22 compared to baseline (worsening = 8.9 [MCID - Minimum clinically importance difference]) - Clinical intervention is defined as a need for NP surgery, SCS use for NP, or need for a biologic.;Timepoint(s) of evaluation of this end point: through the end of the treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Time from randomisation to the earliest post-baseline timepoint with an increase in NPS compared to baseline (increase = 1), which is confirmed at the next assessment at least 4 weeks later (key secondary) - Time from randomisation to the earliest post-baseline timepoint with a clinically meaningful deterioration in SNOT-22 compared to baseline (worsening = 8.9 [MCID] [Minimum clinically importance difference]), which is confirmed at the next assessment at least 4 weeks later (key secondary) - Change from baseline in SNOT-22 [SinoNasal Outcome Test 22 item] - Time from randomisation to the first clinical intervention (need for NP surgery, SCS , need for a biologic) due to nasal polyps recurrence (key secondary) - Time from randomisation to first SCS burst for NP - Time from randomisation to need for subsequent nasal surgery - Change from baseline in the NPSQ [Nasal polyposis symptoms questionnaire] - Change from baseline in DSS [Difficulty with sense of smell] - Change from baseline in the UPSIT [University of Pennsylvania Smell Identification Test] - Change from baseline in the SF-36v2 [Short Form 36-item Health survey, Version 2] - Change from baseline in Lund Mackay score and sinus severity score by Quantitative CT analysis - AEs, vital signs, and clinical laboratory values - Assessments related to AEs [adverse events] cover - Vital signs parameters include systolic and diastolic blood pressure, and pulse, as well as respiration rate and body temperature. Assessments related to vital signs cover: observed value, absolute and percent change from baseline values over time - Serum PK - Benralizumab ADA;Timepoint(s) of evaluation of this end point: through the end of the treatment period | — |
Countries
Austria, Belgium, Canada, Denmark, Germany, Hungary, Poland, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed