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: Active, not recruiting
• Conditions: Nasal Polyposis
• Intervention / Treatment: Biological: Benralizumab 30 mg; Biological: Matched placebo

Detailed Description

Approximately 275 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. 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.

• Study Type: Interventional
• Enrollment (Actual): 296
• 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
  • Bruxelles, Belgium, 1200
    • Research Site
  • Gent, 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, 300052
    • Research Site
  • Urumqi, China, 830054
    • Research Site
  • Wuhan, China, 430022
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  • Xi'an, China, 710004
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  • Xian, China, 710061
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  • Yantai, China, 264000
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• France
  • Marseille, France, 13005
    • Research Site
  • Toulouse CEDEX 09, 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-shi, Japan, 262-0015
    • Research Site
  • Fujisawa-shi, Japan, 251-0052
    • Research Site
  • Hiroshima-shi, 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-shi, Japan, 860-0814
    • Research Site
  • Meguro-ku, Japan, 153-8515
    • Research Site
  • Meguro-ku, Japan, 153-0061
    • Research Site
  • Minato-ku, Japan, 105-8471
    • Research Site
  • Moriguchi-shi, Japan, 570-0074
    • Research Site
  • Nagaoka-shi, Japan, 940-2085
    • Research Site
  • Osaka-shi, 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
  • Elbląg, Poland, 82-300
    • Research Site
  • Kraków, Poland, 31-513
    • Research Site
  • Lublin, Poland, 20-552
    • Research Site
  • Nadarzyn, Poland, 05-830
    • Research Site
  • Poznań, Poland, 60-805
    • Research Site
  • Wrocław, Poland, 53-301
    • Research Site
  • Łodź, Poland, 90-153
    • Research Site
• Russian Federation
  • Izhevsk, Russian Federation, 426061
    • Research Site
  • Penza, Russian Federation, 440067
    • Research Site
  • Saint-Petersburg, Russian Federation, 196158
    • Research Site
• Taiwan
  • Taipei, Taiwan, 235
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei City, Taiwan, 114
    • Research Site
  • Taipei City, Taiwan, 110
    • Research Site
  • Taipei City, Taiwan, 11217
    • Research Site
  • Taoyuan, 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
  • Aydin, Turkey, 09100
    • Research Site
  • Bakirkoy, Turkey, 34147
    • Research Site
  • Izmir, Turkey, 35340
    • Research Site
  • Malatya, Turkey, 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
    • 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
    • Saint 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, 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
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

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 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal Polyp Burden	Change from baseline in endoscopic total nasal polyp score (NPS).	Baseline and Week 56
Patient-reported Nasal Blockage (NB)	Change from baseline in mean nasal blockage score (NBS).	Baseline and week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sense of Smell	Change from baseline in difficulty with sense of smell (DSS) score	Week 56
Sinus Opacification by CT Scan	Change from baseline in Lund Mackay score	Week 56
Disease specific health-related quality of life (HRQoL)	Change from baseline in SinoNasal Outcome Test (SNOT-22) score.	Week 56
Nasal Polyp Surgery	Time to first nasal polyp surgery	Week 56
Systemic corticosteroid (SCS) use	Time to first SCS course for NP	Week 56
Symptoms associated with CRSwNP	Change from baseline in nasal symptom score(s)	Week 56

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment the safety and tolerability of benralizumab	AEs, Vital signs, Clinical Laboratory and ECG	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

• Orchid Study Website

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2019
• Primary Completion (Estimated): August 19, 2024
• Study Completion (Estimated): October 10, 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 (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Asthma; Benralizumab; Nasal Polyposis; Nasal Polyps; Eosinophilic Chronic Rhinosinusitis with Nasal Polyposis
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Nose Diseases; Polyps; Nasal Polyps; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: D3252C00002; 2021-000267-72 (EudraCT Number)

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