Clinical trial NCT04157335: Efficacy and Safety Study of Benralizumab in Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nasal Polyposis
Keywords: Benralizumab
Eosinophilic Chronic Rhinosinusitis with Nasal Polyps
Nasal Polyps
Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-11-08
Enrollment: 295
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Nasal Polyp Burden
timeFrame: Baseline to Week 56
measure: Patient-reported Nasal Blockage (NB)
timeFrame: Baseline to week 56
Secondary outcomes:
measure: Sense of Smell
timeFrame: Baseline to Week 56
measure: Sinus Opacification by CT Scan
timeFrame: Baseline to Week 56
measure: Disease specific health-related quality of life (HRQoL)
timeFrame: Baseline to Week 56
measure: Nasal Polyp Surgery
timeFrame: Baseline to Week 56
measure: Systemic corticosteroid (SCS) use
timeFrame: Baseline to Week 56
measure: Symptoms associated with CRSwNP
timeFrame: Baseline to Week 56
measure: Nasal polyp surgery and/or systemic corticosteroids (SCS）for relief of nasal symptoms
timeFrame: Baseline to Week 56
measure: Nasal polyp surgery and/or systemic corticosteroids (SCS）for relief of nasal symptoms
timeFrame: Baseline to Week 56
measure: Nasal polyp surgery
timeFrame: Baseline to Week 56
measure: Systemic corticosteroids (SCS) use for relief of nasal symptoms
timeFrame: Baseline to Week 56
Other outcomes:
measure: Assessment the safety and tolerability of benralizumab
timeFrame: Baseline to Week 56
Locations:
city: Huntington Beach
country: United States
facility: Research Site
state: California
city: Grand Junction
country: United States
facility: Research Site
state: Colorado
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: White Marsh
country: United States
facility: Research Site
state: Maryland
city: Bronx
country: United States
facility: Research Site
state: New York
city: White Plains
country: United States
facility: Research Site
state: New York
city: Tulsa
country: United States
facility: Research Site
state: Oklahoma
city: Bethlehem
country: United States
facility: Research Site
state: Pennsylvania
city: Fort Worth
country: United States
facility: Research Site
state: Texas
city: McKinney
country: United States
facility: Research Site
state: Texas
city: Saint George
country: United States
facility: Research Site
state: Utah
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Bellingham
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Research Site
city: Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aire
country: Argentina
facility: Research Site
city: San Fernando
country: Argentina
facility: Research Site
city: Herston
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Spearwood
country: Australia
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Quillota
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Talca
country: Chile
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Foshan
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Urumqi
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Xian
country: China
facility: Research Site
city: Yantai
country: China
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Toulouse CEDEX 09
country: France
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Győr
country: Hungary
facility: Research Site
city: Kaposvár
country: Hungary
facility: Research Site
city: Siófok
country: Hungary
facility: Research Site
city: Székesfehérvár
country: Hungary
facility: Research Site
city: Tatabánya
country: Hungary
facility: Research Site
city: Catanzaro
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Fujisawa-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Ichikawa-shi
country: Japan
facility: Research Site
city: Iida-shi
country: Japan
facility: Research Site
city: Kawasaki-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Meguro-ku
country: Japan
facility: Research Site
city: Meguro-ku
country: Japan
facility: Research Site
city: Minato-ku
country: Japan
facility: Research Site
city: Moriguchi-shi
country: Japan
facility: Research Site
city: Nagaoka-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Yoshida-gun
country: Japan
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Elbląg
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Nadarzyn
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Łodź
country: Poland
facility: Research Site
city: Izhevsk
country: Russian Federation
facility: Research Site
city: Penza
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Phitsanulok
country: Thailand
facility: Research Site
city: Aydin
country: Turkey
facility: Research Site
city: Bakirkoy
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Malatya
country: Turkey
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Beijing Tongren Hospital
name: Luo Zhang, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.