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
- 1. Patients with severe NP2. Age: must be 18 to 75 yearsPatients with Eosinophilic Chronic Rhinosinusitis with Nasal Polyps
- Registration Number
- TCTR20190820003
- Lead Sponsor
- AstraZeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending (Not yet recruiting)
- Sex
- All
- Target Recruitment
- 148
1. Capable of giving signed informed consent
2. Subject must be 18 to 75 years of age
3. Patients with bilateral sinonasal polyps that, despite treatment with standard of care including a history of treatment with SCS (oral, parenteral) or prior surgery for NP have severity consistent with a need for surgery
4. CT Lund Mackay score for ethmoid ≥ maxillary as determined by the study Imaging Core lab
5. Blood eosinophil count > 5% or >2% and ≤ 5% as determined by central lab
6. Patients who are on INCS or leukotriene receptor antagonists (LTRAs), need to be at stable dose for at least 30 days prior to V1
7. Willingness to maintain all standard of care treatment for NP stable for the duration of the study
8. SNOT-22 total score ≥ 20 at enrolment (V1)
9. At least 8 days of evaluable daily diary data in the 14-day period prior to randomisation (baseline bi-weekly mean score collected from study Day -13 to study Day 0).
10. At randomisation, a bi-weekly mean NBS ≥ 1.5
11. SNOT-22 total score ≥ 20 at randomisation (V3)
12. For patients that are on INCS or LTRAs, at least 70% compliance with INCS or LTRAs during the run-in period based on daily diary
13. Patients with a minimum weight of 35 kg
14. Negative serum pregnancy test result at V1 and a negative urine pregnancy test at V2 and randomisation for female patients of childbearing potential
15. Women of childbearing potential (WOCBP) must use an effective form of birth control
16. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal
17. Male subjects who are sexually active must be surgically sterile at least one year prior to Visit 1 or must use an adequate method of contraception
1. Patients who have undergone any nasal and/or sinus surgery within 3 months prior to V1
2. Patients with conditions or concomitant disease that makes them non evaluable for the co-primary efficacy endpoint
3. Clinically important comorbidities
4. Any disorder, including but not limited to: cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, autoimmune, haematological, psychiatric, or major physical impairment that is not stable
5. Patients experiencing an asthma exacerbation requiring systemic (oral and/or parenteral) corticosteroids treatment or hospitalisation (>24hrs) for treatment of asthma within 4 weeks prior to V1
ุ6. History of anaphylaxis to any biologic therapy or vaccine
7. Known history of allergy or reaction to any component of the IP formulation
8. History of Guillain-Barré syndrome
9. A helminth parasitic infection diagnosed within 24 weeks prior to V1 and has not been treated with, or has failed to respond to standard of care therapy
10. Current malignancy, or history of malignancy
11. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, during screening/run-in period
12. Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality
13. Chronic stable hepatitis B and C
14. History of known immunodeficiency disorder, including a positive human immunodeficiency virus (HIV) test
15. Infection requiring systemic antibiotics (Ab) or systemic Ab for the treatment of NP within 14 days prior to V1
16. Use of immunosuppressive medication
17. Receipt of any marketed or investigational biologic products
18. Previous receipt of benralizumab.
19. Receipt of immunoglobulin or blood products within 30 days prior to V1.
20. Receipt of live attenuated vaccines 30 days prior to the date of randomisation.
21. Receipt of any investigational drug within 30 days or 5 half-lives whichever is longer prior to randomisation.
22. Receipt of systemic corticosteroid within 4 weeks prior to V1, or a scheduled systemic corticosteroid treatment during the study period.
23. Receipt of herbal remedies or traditional Chinese medicines within 30 days prior to V1
24. Concurrent enrolment in another clinical drug interventional trial
25. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥ 3 times the upper limit of normal (ULN).
26. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
27. Judgment by the investigator that the subject should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
28. Previous randomisation in the present study.
29. Planned major surgical procedures or scheduled NP surgery at the time of the study enrolment and randomisation
30. Initiated or is being maintained on an aspirin desensitization regimen for the management of AERD at the time of study enrolment or during the run-in period.
31. History of alcohol or drug abuse within 12 months prior to V1, based on Investigator’s assessment
32. For women only - currently pregnant (or intend to become pregnant), breastfeeding or lactating
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate the effect of benralizumab on nasal polyp burden and patient-reported nasal blockage (NB At Week 0 (Day 0) to receive either placebo or benralizumab 30 mg SC every 4 weeks for the first 3 d Change from baseline in endoscopic total nasal polyp score (NPS)
- Secondary Outcome Measures
Name Time Method Sinus opacification by CT scan The first up to 74 patients that complete the 56-week treatment will have a 24-week follow-up (FU) p Change from baseline in Lund Mackay Score (LMS)