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

Study Overview
=================
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 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.

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)

Conditions
-----------------
Nasal Polyposis

Intervention / Treatment
-----------------
* Biological: Benralizumab 30 mg
* Biological: Matched placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Female or male patients aged 18 to 75 years inclusive Stable Intranasal corticosteroids (INCS) use for at least 4 weeks prior to enrolment and throughout screening History of treatment with systemic corticosteroids (SCS) or prior surgery for CRSwNP Bilateral sinonasal polyposis with a nasal polyp score (NPS) of 5 at enrolment and randomization (unilateral score of at least 2 for each nostril) Ongoing symptoms for at least 12 weeks prior to enrolment Patient-reported moderate to severe nasal blockage score (NBS) ≥2 at enrolment Bi-weekly mean NBS ≥ 1.5 at randomization SNOT-22 total score ≥ 20 at enrolment and randomization Documented physician-diagnosed asthma Blood eosinophil count of >2% or ≥150/μL at enrolment Exclusion criteria: Any nasal and/or sinus surgery within 3 months prior to enrolment 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; Clinically important comorbidities that may put the patient at risk, or may confound interpretation of clinical efficacy and/or safety results Receipt of SCS for within 4 weeks prior to screening, or a scheduled SCS treatment during the study period. Receipt of any marketed or investigational biologic product within 6 months of enrolment Currently pregnant or breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Benralizumab<br>Benralizumab administered subcutaneously | Biological: Benralizumab 30 mg<br>* 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).<br>|
| Placebo Comparator: Placebo<br>Placebo administered subcutaneously | Biological: Matched placebo<br>* 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).<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Benralizumab, Nasal Polyposis, Eosinophilic Chronic Rhinosinusitis with Nasal Polyposis, Nasal Polyps, Asthma