Efficacy and Safety Study of Benralizumab in Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID) (ORCHID)

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)

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.

Study Overview

• Status: Terminated
• Conditions: Nasal Polyposis; Eosinophilic Chronic Rhinosinusitis
• Intervention / Treatment: Biological: Matched placebo; Biological: Benralizumab 30 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1414AIF
    • Research Site
  • Buenos Aires, Argentina, C1121 ABE
    • Research Site
  • Ciudad de Buenos Aire, Argentina, C1425BEN
    • Research Site
  • San Fernando, Argentina, B1646EBJ
    • Research Site
• Australia
  • Herston, Australia, 4029
    • Research Site
  • Melbourne, Australia, 3004
    • Research Site
  • Spearwood, Australia, 6163
    • Research Site
• Belgium
  • Brussels, Belgium, 1200
    • Research Site
  • Ghent, Belgium, 9000
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
• Bulgaria
  • Plovdiv, Bulgaria, 4001
    • Research Site
  • Sofia, Bulgaria, 1606
    • Research Site
  • Sofia, Bulgaria, 1303
    • Research Site
• Chile
  • Quillota, Chile, 2260000
    • Research Site
  • Santiago, Chile, 7500588
    • Research Site
  • Santiago, Chile, 8150000
    • Research Site
  • Talca, Chile, 3481349
    • Research Site
• China
  • Beijing, China, 100730
    • Research Site
  • Beijing, China, 100044
    • Research Site
  • Beijing, China, 100191
    • Research Site
  • Changchun, China, 130061
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Changsha, China
    • Research Site
  • Changsha, China, 410008
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Chengdu, China, 610072
    • Research Site
  • Chongqing, China, 400042
    • Research Site
  • Foshan, China, 528000
    • Research Site
  • Guangzhou, China, 510000
    • Research Site
  • Guangzhou, China, 510180
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Jinan, China, 250014
    • Research Site
  • Nanchang, China, 330006
    • Research Site
  • Nanjing, China, 210029
    • Research Site
  • Nanning, China, 530021
    • Research Site
  • Qingdao, China, 266071
    • Research Site
  • Shanghai, China, 200065
    • Research Site
  • Shanghai, China, 200092
    • Research Site
  • Tianjin, China, 300050
    • Research Site
  • Wuhan, China, 430022
    • Research Site
  • Xi'an, China, 710061
    • Research Site
  • Xi'an, China, 710004
    • Research Site
  • Yantai, China, 264000
    • Research Site
  • Ürümqi, China, 830054
    • Research Site
• France
  • Marseille, France, 13005
    • Research Site
  • Toulouse, France, 31059
    • Research Site
• Hungary
  • Budapest, Hungary, 1033
    • Research Site
  • Budapest, Hungary, 1046
    • Research Site
  • Győr, Hungary, 9024
    • Research Site
  • Kaposvár, Hungary, 7400
    • Research Site
  • Siófok, Hungary, 8600
    • Research Site
  • Székesfehérvár, Hungary, 8000
    • Research Site
  • Tatabánya, Hungary, 2800
    • Research Site
• Italy
  • Catanzaro, Italy, 88100
    • Research Site
  • Pisa, Italy, 56124
    • Research Site
  • Roma, Italy, 00168
    • Research Site
  • Roma, Italy, 00161
    • Research Site
• Japan
  • Chiba, Japan, 262-0015
    • Research Site
  • Fujisawa-shi, Japan, 251-0052
    • Research Site
  • Hiroshima, Japan, 734-8551
    • Research Site
  • Ichikawa-shi, Japan, 272-0143
    • Research Site
  • Iida-shi, Japan, 395-8505
    • Research Site
  • Kawasaki-shi, Japan, 211-0063
    • Research Site
  • Kumamoto, Japan, 860-0814
    • Research Site
  • Meguro-ku, Japan, 153-8515
    • Research Site
  • Meguro-ku, Japan, 153-0061
    • Research Site
  • Minatoku, Japan, 105-8471
    • Research Site
  • Moriguchi-shi, Japan, 570-0074
    • Research Site
  • Nagaoka-shi, Japan, 940-2085
    • Research Site
  • Osaka, Japan, 540-0008
    • Research Site
  • Shinjuku-ku, Japan, 160-0017
    • Research Site
  • Yoshida-gun, Japan, 910-1193
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-231
    • Research Site
  • Elblag, Poland, 82-300
    • Research Site
  • Krakow, Poland, 31-513
    • Research Site
  • Lublin, Poland, 20-552
    • Research Site
  • Nadarzyn, Poland, 05-830
    • Research Site
  • Poznan, Poland, 60-805
    • Research Site
  • Wroclaw, Poland, 53-301
    • Research Site
  • Łodź, Poland, 90-153
    • Research Site
• Russia
  • Izhevsk, Russia, 426061
    • Research Site
  • Penza, Russia, 440067
    • Research Site
  • Saint Petersburg, Russia, 196158
    • Research Site
• Taiwan
  • Taipei, Taiwan, 235
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 11217
    • Research Site
  • Taipei, Taiwan, 114
    • Research Site
  • Taipei, Taiwan, 110
    • Research Site
  • Taoyuan District, Taiwan, 333
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10400
    • Research Site
  • Bangkok, Thailand, 10700
    • Research Site
  • Chiang Mai, Thailand, 50200
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
  • Phitsanulok, Thailand, 65000
    • Research Site
• Turkey (Türkiye)
  • Aydin, Turkey (Türkiye), 09100
    • Research Site
  • Bakırköy, Turkey (Türkiye), 34147
    • Research Site
  • Izmir, Turkey (Türkiye), 35340
    • Research Site
  • Malatya, Turkey (Türkiye), 44280
    • Research Site
• United States
  • California
    • Huntington Beach, California, United States, 92647
      • Research Site
  • Colorado
    • Grand Junction, Colorado, United States, 81501
      • Research Site
  • Florida
    • Gainesville, Florida, United States, 32605
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40220
      • Research Site
  • Maryland
    • White Marsh, Maryland, United States, 21162
      • Research Site
  • New York
    • The Bronx, New York, United States, 10461
      • Research Site
    • White Plains, New York, United States, 10605
      • Research Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Research Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Research Site
  • Texas
    • Fort Worth, Texas, United States, 76109
      • Research Site
    • McKinney, Texas, United States, 75070
      • Research Site
  • Utah
    • St. George, Utah, United States, 84790
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Research Site
  • Washington
    • Bellingham, Washington, United States, 98225
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53228
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Ho Chi Minh City, Vietnam, 700000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo administered subcutaneously	Biological: Matched placebo; Matching placebo solution for injection in accessorized pre-filled syringe. 1 ml fill volume. Matching placebo subcutaneously will be injected 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).
Experimental: Benralizumab; Benralizumab administered subcutaneously	Biological: Benralizumab 30 mg; Benralizumab is 30 mg/ml solution for injection in accessorized pre-filled syringe, 1 ml fill volume. Benralizumab 30 mg subcutaneously will be injected 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). For OLE, Benralizumab 30 mg subcutaneously will be injected every 4 weeks for the first 3 doses and every 8 weeks for the rest 5 doses. For the patients on Benralizumab treatment during double blind period, placebo will be dosed at the second dose during OLE.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Endoscopic Total Nasal Polyp Score (NPS) at Week 56	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.	Baseline to Week 56
Change From Baseline in Mean Nasal Blockage Score (NBS) at Week 56.	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.	Baseline to week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Difficulty With Sense of Smell (DSS) Score at Week 56.	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.	Baseline to Week 56
Sinus Opacification by CT Scan at Week 56.	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).	Baseline to Week 56
Disease Specific Health-related Quality of Life (HRQoL): Change From Baseline in SinoNasal Outcome Test (SNOT-22) Score at Week 56.	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).	Baseline to Week 56
Time to First Nasal Polyp Surgery	Time to the first surgery for CRSwNP= Start date of the first surgery for CRSwNP - date of randomisation + 1	Baseline to Week 56
Time to First SCS Course for CRSwNP	Time to the first SCS use for CRSwNP = Start date of the first SCS use for CRSwNP - date of randomisation + 1	Baseline to Week 56
Time to First NP Surgery and/or SCS Use for CRSwNP	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	Baseline to Week 56
Change From Baseline in Bi-weekly Mean Nasal Polyps Symptom Diary Total Symptom Score at Week 56.	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.	Baseline to Week 56
Percentage of Participants With Surgery and/or Use SCS for CRSwNP	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)	Baseline to Week 56
Percentage of Participants With Surgery for CRSwNP	Nasal polyps surgery is defined as any procedure involving instruments resulting in incision and removal of tissue (e.g. polypectomy, endoscopic sinus surgery).	Baseline to Week 56
Percentage of Participants With SCS Use for CRSwNP	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)	Baseline to Week 56

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment the safety and tolerability of benralizumab	The number of Adverse events (AEs)/serious adverse events (SAEs).	Baseline to Week 56

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Luo Zhang, Prof. Dr., Beijing Tongren Hospital

Publications and helpful links

General Publications

• Chong LY, Piromchai P, Sharp S, Snidvongs K, Webster KE, Philpott C, Hopkins C, Burton MJ. Biologics for chronic rhinosinusitis. Cochrane Database Syst Rev. 2021 Mar 12;3(3):CD013513. doi: 10.1002/14651858.CD013513.pub3.

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2019
• Primary Completion (Actual): August 6, 2024
• Study Completion (Actual): April 7, 2025

Study Registration Dates

• First Submitted: October 23, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Asthma; Benralizumab; Nasal Polyps; Eosinophilic Chronic Rhinosinusitis with Nasal Polyps
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Nose Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Signs and Symptoms; Asthma; Nasal Polyps; Respiratory System Agents; Anti-Asthmatic Agents; benralizumab
• Other Study ID Numbers: D3252C00002; 2021-000267-72 (EudraCT Number); 2023-507987-38-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No