Bilateral nasal polyposis MedDRA version: 19.0 Level: PT Classification code 10028756 Term: Nasal polyps System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: dupilumab
Product Code: SAR231893
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Dupilumab
Current Sponsor code: SAR231893
Other descriptive name:
Sponsors
SANOFI-AVENTIS RECHERCHE ET DEVELOPPEMENT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Patients with bilateral sinonasal polyposis that despite prior treatment with systemic corticosteroids (SCS) anytime within the past 2 years; and/or have a medical contraindication/intolerance to SCS, and/or had prior surgery for NP at the screening visit, have: -An endoscopic bilateral NPS of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity). -Ongoing symptoms (for at least 8 weeks before V1) of nasal congestion/ blockage/obstruction with moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity of greater than 1 at time of randomization (V2), and another symptom such as loss of smell, rhinorrhea (anterior/posterior). -Signed written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 655 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: - Patients <18 years of age. - Patient who has been previously treated in dupilumab studies. - Patient who has taken: -Biologic therapy/ systemic immunosuppressant to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc.) within 2 months before V1 or 5 half-lives, whichever is longer. -Any experimental monoclonal antibody (mAB) within 5 half-lives or within 6 months before V1 if the half-life is unknown. -Anti-immunoglobulin E therapy (omalizumab) within 130 days prior to V1. -Leukotriene antagonists/modifiers unless patient is on a continuous treatment for at least 30 days prior to V1. - Initiation of allergen immunotherapy within 3 months prior to V1 or a plan to begin therapy or change its dose during the run-in period or the randomized treatment period. - Patients who have undergone any intranasal and/or sinus surgery (including polypectomy) within 6 months before V1. - Patients who have had a sinonasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS. - Patients with conditions/concomitant diseases making them non evaluable at V1 or for the primary efficacy endpoint such as: -Antrochoanal polyps, -Nasal septal deviation that would occlude at least one nostril, -Acute sinusitis, nasal infection or upper respiratory infection, -Ongoing rhinitis medicamentosa, -Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener’s granulomatosis),Young’s syndrome, Kartagener’s syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis, -Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis. - Patients with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil etc.). - Patients with forced expiratory volume (FEV1) 50% or less (of predicted normal). - Patients receiving concomitant treatment prohibited in the study. - Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit. - History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening. - Positive with hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit. - Active chronic or acute infection requiring systemic treatment within 2 weeks before the Baseline visit. - Known or suspected history of immunosuppression. - Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study. - Women unwilling to use adequate birth control, if of reproductive potential and sexually active. Note: The information listed above is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial therefore not all inclusion/ exclusion criteria are listed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of dupilumab compared to placebo on a background of mometasone furoate nasal spray (MFNS) in reducing nasal congestion/obstruction (NC) severity and endoscopic nasal polyposis score (NPS) in patients with bilateral nasal polyposis (NP). In addition for Japan, reduction in computed tomography (CT) scan opacification of the sinuses will be also a coprimary objective.;Secondary Objective: -To evaluate the efficacy of dupilumab in improving total symptoms score (TSS). -To evaluate the efficacy of dupilumab in improving sense of smell. -To evaluate the efficacy of dupilumab in reducing CT scan opacification of the sinuses (Primary objective for Japan). -To evaluate ability of dupilumab in reducing proportion of patients requiring treatment with oral corticosteroids or NP surgery. -To evaluate the effect of dupilumab on patient reported outcomes and health related quality of life outcome by sinonasal outcome test-22 (SNOT-22). -To evaluate efficacy with various regimen. -To evaluate the effect of dupilumab in the subgroups of patients with prior surgery and co-morbid asthma (including non-steroid antiinflammatory drug [NSAID] exacerbated respiratory disease NERD]). -To evaluate the safety of dupilumab in patients with bilateral NP. -To evaluate functional dupilumab concentrations (systemic exposure) and incidence of treatmentemergent anti-drug antibodies (ADA).;Primary end point(s): 1- Change from baseline in NC symptom severity score based on the patient daily morning assessment 2- Change from baseline in NPS as assessed by nasal endoscopy 3- Change from baseline in sinus opacifications as assessed by CT scans using Lund Mackay Score (For Japan only);Timepoint(s) of evaluation of this end point: 1-2-3 : From baseline to Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1- Change from baseline in TSS 2- Change from baseline in University of Pennsylvania Smell Identification Test 3- Change from baseline in severity of decreased/ loss of smell as assessed by the patient 4- Change from baseline in sinus opacifications as assessed by CT scans using Lund Mackay Score (This endpoint will not be assessed as a secondary endpoint for Japan as it is already a co-primary endpoint). 5- Change from baseline in in sinonasal outcome test-22 (SNOT-22) 6- Proportion of patients during study treatment receiving oral corticosteroid (OCS) for NP and/or planned to under surgery for nasal polyps 7- Change from baseline in NC for q2w (Arm A) versus placebo (Arm C) 8- Change from baseline in NPS for q2w (Arm A) versus placebo (Arm C) 9- Change from baseline in NC for q2w/q4w (Arm B) versus placebo (Arm C) 10- Change from baseline in NPS for q2w/q4w (Arm B) versus placebo (Arm C);Timepoint(s) of evaluation of this end point: 1-2-3-4-5 : From baseline to Week 24 6: 52 weeks 7-8-9-10 : From baseline to Week 52 | — |
Countries
Argentina, Australia, Belgium, Canada, Chile, Israel, Japan, Mexico, Portugal, Russian Federation, Spain, Sweden, Turkey, United States
Contacts
Public ContactCountry Team Manager Sweden
Sanofi AB
Outcome results
None listed