Chronic rhinosinusitis without nasal polyposis MedDRA version: 20.1 Level: PT Classification code 10009137 Term: Chronic sinusitis System Organ Class: 10021881 - Infections and infestations
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 & Développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Part A only: Participant must be at least 18 years of age at the time of signing the informed consent form (ICF). - Part B only: Participant must be at least 12 years of age (or the minimum legal age for adolescents in the country of the investigational site) at the time of signing the ICF. - Participants must have bilateral inflammation of paranasal sinuses in CT scan with LMK =8 and bilateral ethmoid opacification before randomization. - Participants must have ongoing symptoms of loss of smell and rhinorrhea (anterior/posterior) of any severity, with or without facial pain/pressure for at least 12 consecutive weeks by Visit 1. - Participants must have ongoing symptoms of nasal congestion (NC)/obstruction at least 12 consecutive weeks before Visit 1 and a NC score of = 2 at Visit 1 (day score) and Visit 2 (weekly average score). - Participants must have sTSS (NC, rhinorrhea, facial pain/pressure) =5 at Visit 1 (day score) and Visit 2 (weekly average score). - Participants must have one of the 2 following features: o Prior sinonasal surgery (see note at end of section 5.2 for definitions of sinonasal surgery) for CRS, o Comorbid asthma, o Treatment with SCS therapy for CRS as defined by any dose and duration within the prior 2 years before screening (Visit 1) or intolerance/contraindication to SCS. - For Part B only: participants who have a blood eosinophil count =300 cells/mm3 at Screening - Body weight =30 kg. Are the trial subjects under 18? yes Number of subjects for this age range: 9 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 371 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 44
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: - Patients with nasal conditions/concomitant nasal diseases such as nasal polyposis in endoscopy at Visit 1 or with history of nasal polyposis etc., making them non-evaluable at Visit 1 or for the primary efficacy - Nasal cavity malignant tumor and benign tumors. - Forced expiratory volume (FEV1) =50% of predicted normal at Visit 1. - Radiologic suspicion or confirmed invasive or expansive fungal rhinosinusitis. - Severe concomitant illness(es) that, in the investigator’s judgment, would adversely affect the patient’s participation in the study - Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated. - Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection - Known or suspected immunodeficiency - History of malignancy within 5 years before Visit 1, except completely treated in situ carcinoma of the cervix, and completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin. - Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit 1 or during the screening period. - History of systemic hypersensitivity or anaphylaxis to dupilumab or any of its excipients. - Patients in prior dupilumab clinical trial or have been treated with commercially available dupilumab within 12 months or who discontinued dupilumab use due to adverse event. - Patients who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as Xhance™, during screening period. - Participants on unstable dose of INCS spray 4 weeks prior to Screening Visit (Visit1) and during screening period. - Patients who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit 1. - Patients who have taken: o Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to Visit 1 o Any investigational mAb within 5 half-lives prior to Visit 1 o Anti-IgE therapy (omalizumab) within 4 months prior to Visit 1. -Treatment with a live (attenuated) vaccine within 4 weeks prior to Visit 1 - Leukotriene antagonists/modifiers unless patient is on a continuous treatment for at least 30 days prior to Visit 1. - Initiation of allergen immunotherapy within 3 months prior to Visit 1 or a plan to begin therapy or change its dose during the screening or treatment period. - Patients received SCS during screening period(between Visit 1 and Visit 2). - Either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to Screening Visit (Visit 1).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Part A: To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on computerized tomography (CT) scan and sinus total symptom score (sTSS) compared to placebo •Part B: To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on CT scan and sinus total symptom score (sTSS) compared to placebo ;Secondary Objective: Part A : Evaluate the: 1.efficacy of dupi as assessed by the reduction at Week 52 in sinus opacification on CT scan and sTSS 2.efficacy of dupi in improving CRSsNP symptoms at Weeks 24 and 52 3.effect of dupi on health related quality of life at Weeks 24 and 52 4.effect of dupi on CRSsNP overall disease severity at Weeks 24 and 52 5.effect of dupi at Weeks 24 and 52 in the subgroups of participants with comorbid asthma 6.ability of dupi to reduce the incidence of participants with CRSsNP worsening/acute sinusitis who require treatment with antibiotics, SCS or sinus surgery 7.effects of dupi on transcriptomic signatures associated with CRSsNP and type 2 inflammation 8.effect of dupi in the subgroup with screening blood eosinophils count =300 cells/mm3 9.safety and tolerability of dupi in CRSsNP patients 10.pharmacokinetics (PK) of dupi in CRSsNP patients 11.Assessment of immunogenicity to dupi over time Compared to placebo Part B Same as above except at Week 24 only;Primary end point(s): 1 - Part A and B: Change from baseline to Week 24 in opacification of sinuses assessed by CT scan using the Lund Mackay (LMK) score ; LMK total score is based on assessment of the CT scan findings for each sinus area. The extent of opacification is rated between 0 (normal) to 24 (total opacification). 2 - Part A and B: Change from baseline to Week 24 in sTSS ; The sinus Total Symptom Score (sTSS) is a composite score derived from the following individual items: nasal congestion (NC), anterior/posterior rhinorrhea, and facial pain/pressure. The total score ranges from | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Part A: Change from baseline to Week 52 in opacification of sinuses assessed by CT scan using the LMK score 2 - Part A: Change from baseline to Week 52 in sTSS 3 - Part A and B: Change from baseline in NC symptom severity score 4 - Part A and B: Change from baseline in anterior/posterior rhinorrhea severity score 5 - Part A and B: Change from baseline in facial pain/pressure severity score 6 - Part A and B: Change from baseline in loss of smell symptom severity score 7 - Part A and B: Change from baseline in University of Pennsylvania smell identification test (UPSIT) 8 - Part A and B: Change from baseline in Sino-Nasal Outcome Test-22 item (SNOT 22) 9 - Part A and B: Change from baseline in rhinosinusitis severity visual analog scale (VAS) 10 - Part A and B: Change from baseline in forced expiratory volume (FEV1) in CRSsNP with asthma population 11 - Part A and B: Change from baseline in asthma control questionnaire 6 items (ACQ-6) in CRSsNP with asthma population 12 - Part A and B: Change from baseline in opacification of sinuses assessed by CT scan using the LMK score in CRSsNP with asthma population 13 - Part A and B: Change from baseline in sTSS in CRSsNP with asthma population 14 - Part A and B: Proportion of participants with CRSsNP worsening/acute sinusitis during the planned study treatment period 15 - Part A and B: Annualized rate of SCS course during the planned study treatment period 16 - Part A and B: Normalized Enrichment Score (NES) for the relative change from baseline in the type 2 inflammation transcriptome signature 17 - Part A: Change from baseline to Weeks 24 and 52 in opacification of sinuses assessed by CT scan using LMK score in the screening blood eosinophil count =300 cells/mm3 population 18 - Part A: Change from baseline to Weeks 24 and 52 in sTSS in the screening blood eosinophil count =300 cells/mm3 population 19 - Part A: Change from baseline in NC symptom severity score in the screening | — |
Countries
Belgium, Canada, China, Hungary, Japan, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Ukraine, United States
Contacts
Public ContactBrigitte De Witte
Sanofi Belgium
Outcome results
None listed