Brief Summary
This is a randomized, double-blind, placebo-controlled, parallel-group, international, multicenter, Phase 3 study to evaluate the efficacy and safety of repeat dosing of benralizumab 30 mg administered subcutaneously (SC) versus placebo in patients with severe nasal polyposis.
Brief Title
Efficacy and Safety Study of Benralizumab in Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID)
Detailed Description
Approximately 250 patients will be randomized to receive benralizumab 30 mg SC or matching placebo. After enrolment, eligible patients will enter a 6-week screening/run in period. Patients who meet eligibility criteria will be randomised 1:1 at Week 0 (Day 0) to receive either placebo or benralizumab 30 mg SC every 4 weeks for the first 3 doses (Weeks 0, 4 and 8) and every 8 weeks thereafter (Weeks 16, 24, 32, 40 and 48). An end of treatment visit will be conducted at Week 56.All patients who complete the 56-week DB treatment period on investigational product (IP) may be eligible to continue into around one year OLE, during which all patients will receive 8 doses of benralizumab 30 mg. Patients in Benra arm during DB period will receive one dummy dose for the second dose during OLE. The last study visit will occur at 8 weeks after the last dose of IP (Week 112/FU). Patients who do not enter OLE, will have their last study visit at Week 56 (EoDB) for follow-up and without administration of IP.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Nasal Polyposis
Eligibility Criteria
Inclusion criteria:
1. Female or male patients aged 18 to 75 years inclusive
2. Stable Intranasal corticosteroids (INCS) use for at least 4 weeks prior to enrolment and throughout screening and DB period
3. History of treatment with systemic corticosteroids (SCS) or prior surgery for CRSwNP
4. Bilateral sinonasal polyposis with a nasal polyp score (NPS) of 5 at enrolment and randomization (unilateral score of at least 2 for each nostril)
5. Ongoing symptoms for at least 12 weeks prior to enrolment
6. Patient-reported moderate to severe nasal blockage score (NBS) ≥2 at enrolment
7. Bi-weekly mean NBS ≥ 1.5 at randomization
8. SNOT-22 total score ≥ 20 at enrolment and randomization
9. Documented physician-diagnosed asthma
10. Blood eosinophil count of \>2% or ≥150/μL at enrolment
11. LMS E≥M for Asian
Exclusion criteria:
1. Any nasal and/or sinus surgery within 3 months prior to enrolment
2. Patients with conditions that makes them non evaluable for the co-primary efficacy endpoint including but not limited to:
* Unilateral antrochoanal polyps
* Nasal septal deviation that occludes at least one nostril
* Current rhinitis medicamentosa
* Allergic fungal rhinosinusitis or allergic fungal sinusitis;
3. Clinically important comorbidities (other eosinophil-driven diseases but CRSwNP) that may put the patient at risk, or may confound interpretation of clinical efficacy and/or safety results
4. Receipt of SCS for within 4 weeks prior to screening, or a scheduled SCS treatment during the study period.
5. Receipt of any marketed or investigational biologic product within 6 months of enrolment
6. Currently pregnant or breastfeeding
1. Female or male patients aged 18 to 75 years inclusive
2. Stable Intranasal corticosteroids (INCS) use for at least 4 weeks prior to enrolment and throughout screening and DB period
3. History of treatment with systemic corticosteroids (SCS) or prior surgery for CRSwNP
4. Bilateral sinonasal polyposis with a nasal polyp score (NPS) of 5 at enrolment and randomization (unilateral score of at least 2 for each nostril)
5. Ongoing symptoms for at least 12 weeks prior to enrolment
6. Patient-reported moderate to severe nasal blockage score (NBS) ≥2 at enrolment
7. Bi-weekly mean NBS ≥ 1.5 at randomization
8. SNOT-22 total score ≥ 20 at enrolment and randomization
9. Documented physician-diagnosed asthma
10. Blood eosinophil count of \>2% or ≥150/μL at enrolment
11. LMS E≥M for Asian
Exclusion criteria:
1. Any nasal and/or sinus surgery within 3 months prior to enrolment
2. Patients with conditions that makes them non evaluable for the co-primary efficacy endpoint including but not limited to:
* Unilateral antrochoanal polyps
* Nasal septal deviation that occludes at least one nostril
* Current rhinitis medicamentosa
* Allergic fungal rhinosinusitis or allergic fungal sinusitis;
3. Clinically important comorbidities (other eosinophil-driven diseases but CRSwNP) that may put the patient at risk, or may confound interpretation of clinical efficacy and/or safety results
4. Receipt of SCS for within 4 weeks prior to screening, or a scheduled SCS treatment during the study period.
5. Receipt of any marketed or investigational biologic product within 6 months of enrolment
6. Currently pregnant or breastfeeding
Inclusion Criteria
Inclusion criteria:
1. Female or male patients aged 18 to 75 years inclusive
2. Stable Intranasal corticosteroids (INCS) use for at least 4 weeks prior to enrolment and throughout screening and DB period
3. History of treatment with systemic corticosteroids (SCS) or prior surgery for CRSwNP
4. Bilateral sinonasal polyposis with a nasal polyp score (NPS) of 5 at enrolment and randomization (unilateral score of at least 2 for each nostril)
5. Ongoing symptoms for at least 12 weeks prior to enrolment
6. Patient-reported moderate to severe nasal blockage score (NBS) ≥2 at enrolment
7. Bi-weekly mean NBS ≥ 1.5 at randomization
8. SNOT-22 total score ≥ 20 at enrolment and randomization
9. Documented physician-diagnosed asthma
10. Blood eosinophil count of \>2% or ≥150/μL at enrolment
11. LMS E≥M for Asian
1. Female or male patients aged 18 to 75 years inclusive
2. Stable Intranasal corticosteroids (INCS) use for at least 4 weeks prior to enrolment and throughout screening and DB period
3. History of treatment with systemic corticosteroids (SCS) or prior surgery for CRSwNP
4. Bilateral sinonasal polyposis with a nasal polyp score (NPS) of 5 at enrolment and randomization (unilateral score of at least 2 for each nostril)
5. Ongoing symptoms for at least 12 weeks prior to enrolment
6. Patient-reported moderate to severe nasal blockage score (NBS) ≥2 at enrolment
7. Bi-weekly mean NBS ≥ 1.5 at randomization
8. SNOT-22 total score ≥ 20 at enrolment and randomization
9. Documented physician-diagnosed asthma
10. Blood eosinophil count of \>2% or ≥150/μL at enrolment
11. LMS E≥M for Asian
Gender
All
Gender Based
false
Keywords
Benralizumab
Eosinophilic Chronic Rhinosinusitis with Nasal Polyps
Nasal Polyps
Asthma
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT04157335
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D3252C00002
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Multicentre, Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Benralizumab in Patients With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID)
Primary Outcomes
Outcome Description
Change from baseline in endoscopic total nasal polyp score (NPS).
Outcome Measure
Nasal Polyp Burden
Outcome Time Frame
Baseline to Week 56
Outcome Description
Change from baseline in mean nasal blockage score (NBS).
Outcome Measure
Patient-reported Nasal Blockage (NB)
Outcome Time Frame
Baseline to week 56
Secondary Ids
Secondary Id
2023-507987-38-00
Secondary Id
2021-000267-72
Secondary Outcomes
Outcome Description
Change from baseline in difficulty with sense of smell (DSS) score
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Sense of Smell
Outcome Description
Change from baseline in Lund Mackay score
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Sinus Opacification by CT Scan
Outcome Description
Change from baseline in SinoNasal Outcome Test (SNOT-22) score.
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Disease specific health-related quality of life (HRQoL)
Outcome Description
Time to first nasal polyp surgery
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Nasal Polyp Surgery
Outcome Description
Time to first SCS course for CRSwNP
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Systemic corticosteroid (SCS) use
Outcome Description
Change from baseline in nasal symptom score(s)
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Symptoms associated with CRSwNP
Outcome Description
Time to first NP surgery and/or SCS use for CRSwNP
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Nasal polyp surgery and/or systemic corticosteroids (SCS）for relief of nasal symptoms
Outcome Description
Proportion of patients with NP urgery and/orSCS use for CRSwNP
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Nasal polyp surgery and/or systemic corticosteroids (SCS）for relief of nasal symptoms
Outcome Description
Proportion of patients with surgery for CRSwNP
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Nasal polyp surgery
Outcome Description
Proportion of patients with SCS use for CRSwNP
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Systemic corticosteroids (SCS) use for relief of nasal symptoms
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Nadeem Akbar
Investigator Email
nakbar@montefiore.org
Investigator Phone
501-9690-6717