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

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Nasal Polyposis

Treatments: Biological: Benralizumab 30 mg; Biological: Matched placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04157335

D3252C00002

2021-000267-72 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 296 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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296 participants in 2 patient groups, including a placebo group

Benralizumab

Experimental group

Description:

Benralizumab administered subcutaneously

Treatment:

Biological: Benralizumab 30 mg

Placebo

Placebo Comparator group

Description:

Placebo administered subcutaneously

Treatment:

Biological: Matched placebo