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

Nasal Polyposis Clinical Trial

— ORCHID  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04157335
• Other study ID #: D3252C00002
• Secondary ID: 2021-000267-72
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 25, 2019
• Est. completion date: October 10, 2025

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 296
• Est. completion date: October 10, 2025
• Est. primary completion date: August 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Nasal Polyposis
• Nasal Polyps
• Rhinosinusitis

Intervention

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).
• 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).

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Ciudad de Buenos Aire
Argentina	Research Site	San Fernando
Australia	Research Site	Herston
Australia	Research Site	Melbourne
Australia	Research Site	Spearwood
Belgium	Research Site	Bruxelles
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Chile	Research Site	Quillota
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Talca
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Foshan
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Jinan
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Tianjin
China	Research Site	Urumqi
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Xian
China	Research Site	Yantai
France	Research Site	Marseille
France	Research Site	Toulouse CEDEX 09
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Kaposvár
Hungary	Research Site	Siófok
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Tatabánya
Italy	Research Site	Catanzaro
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Roma
Japan	Research Site	Chiba-shi
Japan	Research Site	Fujisawa-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Ichikawa-shi
Japan	Research Site	Iida-shi
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Meguro-ku
Japan	Research Site	Meguro-ku
Japan	Research Site	Minato-ku
Japan	Research Site	Moriguchi-shi
Japan	Research Site	Nagaoka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Yoshida-gun
Poland	Research Site	Bydgoszcz
Poland	Research Site	Elblag
Poland	Research Site	Kraków
Poland	Research Site	Lodz
Poland	Research Site	Lublin
Poland	Research Site	Nadarzyn
Poland	Research Site	Poznan
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Saint-Petersburg
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Phitsanulok
Turkey	Research Site	Aydin
Turkey	Research Site	Bakirkoy
Turkey	Research Site	Izmir
Turkey	Research Site	Malatya
United States	Research Site	Bellingham	Washington
United States	Research Site	Bethlehem	Pennsylvania
United States	Research Site	Bronx	New York
United States	Research Site	Fort Worth	Texas
United States	Research Site	Gainesville	Florida
United States	Research Site	Grand Junction	Colorado
United States	Research Site	Huntington Beach	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	McKinney	Texas
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Richmond	Virginia
United States	Research Site	Saint George	Utah
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	White Marsh	Maryland
United States	Research Site	White Plains	New York
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Belgium,  Bulgaria,  Chile,  China,  France,  Hungary,  Italy,  Japan,  Poland,  Russian Federation,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessment the safety and tolerability of benralizumab	AEs, Vital signs, Clinical Laboratory and ECG	Week 56
Primary	Nasal Polyp Burden	Change from baseline in endoscopic total nasal polyp score (NPS).	Baseline and Week 56
Primary	Patient-reported Nasal Blockage (NB)	Change from baseline in mean nasal blockage score (NBS).	Baseline and week 56
Secondary	Sense of Smell	Change from baseline in difficulty with sense of smell (DSS) score	Week 56
Secondary	Sinus Opacification by CT Scan	Change from baseline in Lund Mackay score	Week 56
Secondary	Disease specific health-related quality of life (HRQoL)	Change from baseline in SinoNasal Outcome Test (SNOT-22) score.	Week 56
Secondary	Nasal Polyp Surgery	Time to first nasal polyp surgery	Week 56
Secondary	Systemic corticosteroid (SCS) use	Time to first SCS course for NP	Week 56
Secondary	Symptoms associated with CRSwNP	Change from baseline in nasal symptom score(s)	Week 56