Efficacy and Safety Study of Benralizumab for Patients with Severe Nasal Polyposis
- Conditions
- asal polyposisMedDRA version: 20.0Level: LLTClassification code 10028754Term: Nasal polypSystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2017-003675-61-PL
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 400
1. Capable of giving signed informed consent, which includes compliance
with the requirements and restrictions, listed in the informed consent
form (ICF) and in protocol.
2. Provision of signed and dated, written informed consent form (ICF)
prior to any mandatory study specific procedures, sampling, and
analyses and according to international guidelines and/or applicable EU
guidelines.
3. Provision of signed and dated written genetic informed consent in
patients that agree to participate in the genetic sampling, prior to
collection of sample for genetic analysis.
4. Female or male patients aged 18 to 75 years inclusive, at the time of
signing the ICF.
5. Patients with bilateral sinonasal polyposis that, despite treatment
with a stable dose of intranasal corticosteroids (INCS) for at least 4
weeks prior to V1, in addition to a history of treatment with systemic
corticosteroids (SCS -oral, parenteral) or prior surgery for nasal
polyposis (NP), have severity consistent with a need for surgery as
described by:
- A minimum total Nasal Polyp Score (NPS) of 5 out of a maximum score
of 8 (with a unilateral score of at least 2 for each nostril) at V1 and
continuously maintained at V2 to meet the randomization criterion, as
determined by the study Imaging Core Lab;
- Ongoing symptoms for at least 12 weeks prior to V1;
- Patient-reported moderate to severe nasal blockage score (NBS) 2 or 3
over the 2-weeks prior to V1 (2-week recall assessment of symptoms,
scores 0-none to 3-severe).
6. SNOT-22 total score = 30 at enrolment (V1).
Patient must meet the following criteria (points 7-10) at the
randomization visit (V3):
7. At least 8 days of evaluable daily diary data in the 14-day period prior
to randomization (baseline bi-weekly mean score collected from study
Day -13 to study Day 0).
8. At randomization, a bi-weekly mean NBS = 1.5.
9. SNOT-22 total score = 30 at randomization (V3).
10. At least 70% compliance with INCS during the run-in period based
on daily diary.
11. Patients with a minimum weight of 40kg.
12. Negative serum pregnancy test result at V1 and a negative urine
pregnancy test at randomization for female patients of childbearing
potential.
13. Women of childbearing potential (WOCBP) must use an effective
form of birth control (confirmed by the Investigator) eg, total sexual
abstinence, a vasectomized sexual partner, Implanon. Female
sterilization by tubal occlusion, any effective IUD intrauterine
device/IUS levonorgestrel Intrauterine system, Depo-ProveraTM
injections, oral contraceptive, Evra PatchTM, or NuvaringTM. Women of
childbearing potential must agree to use highly effective method of birth
control, as defined above, from enrolment, throughout the study
duration and for 16 weeks after the last dose of investigational product
(IP).
14. Women not of childbearing potential are defined as women who are
either permanently sterilized (hysterectomy, bilateral oophorectomy, or
bilateral salpingectomy), or who are postmenopausal. Women will be
considerd postmenopausal if they have been amenorrheic for 12 months
prior to the planned date of the randomization without alternative
medical cause. The following age specific requirements apply:
- Women <50 years old are considered postmenopausal if they have
been amenorrheic for 12 months or more following cessation of
exogenous hormonal treatment and if follicle stimulating hormone (FSH)
levels are in the postmenopausal range;
- Wom
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 such as:
- Unilateral antrochoanal polyps;
- Nasal septal deviation that occludes at least one nostril;
- Acute sinusitis, nasal infection, or upper respiratory infection at screening or in the 2 weeks before screening;
- Current rhinitis medicamentosa;
- Allergic fungal rhinosinusitis (AFRS) or Allergic fungal sinusitis (AFS);
- Nasal cavity tumors.
3. Clinically important comorbidities that could confound interpretation of clinical efficacy results including, but not limited to: active upper or lower respiratory tract infection, cystic fibrosis, primary ciliary dyskinesia, eosinophilic diseases other than asthma (eg, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic granulomatosis with polyangitis [Churg-Strauss syndrome], hypereosinophilic syndromes), granulomatosis with polyangitis (Wegener's granulomatosis), Young's syndrome, etc.
4. Any disorder, including but not limited to: cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator or AstraZeneca and could:
- Affect the safety of the patient throughout the study;
- Influence the findings of the studies or their interpretations;
- Impede the patient's ability to complete the entire duration of study.
5. Patients experiencing an asthma exacerbation requiring systemic (oral and/or parenteral) corticosteroids treatment or hospitalization (>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 with specific exceptions.
11. Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality obtained during the screening/run-in period, which may put the patient at risk or interfere with study assessments.
12. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology (confirmed by additional testing, e.g. hepatitis C RNA test, if indicated), or a positive medical history for hepatitis B or C. (Note: Patients with history of hepatitis B vaccination without history of hepatitis B are allowed to enrol).
13. History of known immunodeficiency disorder, including a positive human immunodeficiency virus (HIV) test.
14. Infection requiring systemic antibiotics (Ab) within 14 days prior to V1.
15. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, or any experimental anti-inflammatory therapy) within 3 months prior to V1.
16. Receipt of any marketed or investigational biologic products (monoclonal or polyclonal antibody) within 6 months or 5 half-lives, whichever is longer, prior to V1. This also applies to patients who previously participated in clinical studies and were treated with monoclonal antibodies (e.g. mepolizumab, reslizumab, dupilumab, omalizumab). Note that this restriction do not ap
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method