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 (Open Label Extension), 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 (Open Label Extension). The last study visit will occur at 8 weeks after the last dose of IP (Week 112/FU). Patients who do not enter OLE (Open Label Extension), 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
Eosinophilic Chronic Rhinosinusitis
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
Terminated
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
The total nasal polyp score (NPS) is the sum of the right and left nostril scores (maximum of 8), as evaluated by nasal endoscopy. Higher scores indicate greater symptom severity. The left and right score will be based on a central read with a scale from 0 to 4. Each nasal endoscopy is evaluated by two independent physician reviewers.
Outcome Measure
Change From Baseline in Endoscopic Total Nasal Polyp Score (NPS) at Week 56
Outcome Time Frame
Baseline to Week 56
Outcome Description
The NBS is an item in the NPSD. Patients were asked to rate the severity of their worst nasal blockage over the past 24 hours using the following response options: 0 - none; 1 - mild; 2 - moderate; 3 - severe. Higher scores indicate greater symptom severity. The NBS and the changes from baseline were summarised every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Bi-weekly mean were calculated if at least 8 days in each 14-day period had evaluable data; otherwise, the biweekly mean was set to missing.
Outcome Measure
Change From Baseline in Mean Nasal Blockage Score (NBS) at Week 56.
Outcome Time Frame
Baseline to week 56
Secondary Ids
Secondary Id
2023-507987-38-00
Secondary Id
2021-000267-72
Secondary Outcomes
Outcome Description
The DSS is an item in the NPSD. Patients were asked to rate the severity of their worst difficulty with sense of smell over the past 24 hours using the following response options: 0-none; 1-mild; 2-moderate; 3-severe. Higher scores indicate greater symptom severity. The DSS and the changes from baseline were summarised every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Bi-weekly mean of DSS was calculated if at least 8 days in each 14-day period have evaluable data; otherwise the bi-weekly mean was set to missing.
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Change From Baseline in Difficulty With Sense of Smell (DSS) Score at Week 56.
Outcome Description
Change from baseline in Lund- Mackay score (LMS). The Lund-Mackay score scoring system is used to provide a quantitative assessment of nasal sinuses on sinus CT scans. Based on the sinus CT images, the five sinuses (maxillary, anterior ethmoid, posterior ethmoid, sphenoid and frontal) on each site are score by central radiologist as follows: (0-Normal; 1-Partial Opacification; 2-Total Opacification). The osteomeatal complex is scored for right and left sides (0 - Not occluded; 2- Occluded). The total score ranges from 0 to 24 (higher scores indicate poorer outcomes).
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Sinus Opacification by CT Scan at Week 56.
Outcome Description
SinoNasal Outcome Test 22 scores are participant-reported and assess physical problems, functional limitations and emotional consequences of SinoNasal conditions. Patient-reported symptom severity and symptom impact over the past 2 weeks are captured via a 6-point scale (0-No Problem to 5-Problem as bad as it can be). The total score is the sum of item scores and has a range from 0 to 110 (higher scores indicate poorer outcomes).
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Disease Specific Health-related Quality of Life (HRQoL): Change From Baseline in SinoNasal Outcome Test (SNOT-22) Score at Week 56.
Outcome Description
Time to the first surgery for CRSwNP= Start date of the first surgery for CRSwNP - date of randomisation + 1
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Time to First Nasal Polyp Surgery
Outcome Description
Time to the first SCS use for CRSwNP = Start date of the first SCS use for CRSwNP - date of randomisation + 1
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Time to First SCS Course for CRSwNP
Outcome Description
Time to first surgery and/or SCS use for CRSwNP = earlier date of (start date of first surgery for CRSwNP, start date of first SCS use for CRSwNP) - date of randomisation + 1
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Time to First NP Surgery and/or SCS Use for CRSwNP
Outcome Description
The participant completed the nasal polyposis symptom diary each morning throughout the study. The participant was asked to consider their experience with nasal polyposis/nasal polyps over the past 24 hours when responding to each question. Participants were asked to report their experience with nasal polyposis symptoms (nasal blockage, nasal congestion, runny nose, postnasal drip (mucus drainage down the throat), headache, facial pain, facial pressure, difficulty with sense of smell). Participants reported the severity of each symptom and symptom impact at its worst using a 4-point verbal rating scale (0-None to 3-Severe). A total symptom score (range from 0 to 24) was calculated by taking the sum of the 8 equally weighted symptom items. Higher scores indicate greater symptom severity.
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Change From Baseline in Bi-weekly Mean Nasal Polyps Symptom Diary Total Symptom Score at Week 56.
Outcome Description
Nasal polyps surgery is defined as any procedure involving instruments resulting in incision and removal of tissue (e.g. polypectomy, endoscopic sinus surgery).
An SCS course can be considered as a new course if the start date is preceded by at least 7 days after the end date of the last SCS course for CRSwNP (i.e. start date of the new course - end date of the last course \> 7)
An SCS course can be considered as a new course if the start date is preceded by at least 7 days after the end date of the last SCS course for CRSwNP (i.e. start date of the new course - end date of the last course \> 7)
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Percentage of Participants With Surgery and/or Use SCS for CRSwNP
Outcome Description
Nasal polyps surgery is defined as any procedure involving instruments resulting in incision and removal of tissue (e.g. polypectomy, endoscopic sinus surgery).
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Percentage of Participants With Surgery for CRSwNP
Outcome Description
An SCS course can be considered as a new course if the start date is preceded by at least 7 days after the end date of the last SCS course for CRSwNP (i.e. start date of the new course - end date of the last course \> 7)
Outcome Time Frame
Baseline to Week 56
Outcome Measure
Percentage of Participants With SCS Use for CRSwNP
See Also Links
Url
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
Categories Mesh Debug
Head & Neck --- NASAL POLYPS
Head & Neck --- NOSE DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
Head & Neck --- OTORHINOLARYNGOLOGIC DISEASES
Asthma and Other Respiratory Diseases --- BRONCHIAL DISEASES
Lung --- BRONCHIAL DISEASES
Lung --- LUNG DISEASES, OBSTRUCTIVE
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY HYPERSENSITIVITY
Lung --- RESPIRATORY HYPERSENSITIVITY
Lung --- HYPERSENSITIVITY, IMMEDIATE
Lung --- HYPERSENSITIVITY
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
NASAL POLYPS
ASTHMA
NOSE DISEASES
RESPIRATORY TRACT DISEASES
OTORHINOLARYNGOLOGIC DISEASES
POLYPS
PATHOLOGICAL CONDITIONS, ANATOMICAL
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
BRONCHIAL DISEASES
LUNG DISEASES, OBSTRUCTIVE
LUNG DISEASES
RESPIRATORY HYPERSENSITIVITY
HYPERSENSITIVITY, IMMEDIATE
HYPERSENSITIVITY
IMMUNE SYSTEM DISEASES
BENRALIZUMAB