Primary Objective: To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on computerized tomography (CT) scan in the dupilumab group only Secondary Objectives: * 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 * To evaluate the safety and tolerability of dupilumab in CRSsNP patients compared to placebo * To evaluate the pharmacokinetics (PK) of dupilumab in CRSsNP patients compared to placebo * Assessment of immunogenicity to dupilumab over time compared to placebo
The duration of study for each participant will include 2-4 weeks of screening period, 24-52 weeks randomized investigational medicinal product (IMP) intervention period and 12 weeks of follow-up period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
71
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
Sacramento Ear, Nose & Throat Site Number : 8400010
Roseville, California, United States
Bensch Clinical Research LLC Site Number : 8400015
Stockton, California, United States
Colorado Allergy and Asthma Centers, PC Site Number : 8400003
Denver, Colorado, United States
University of Missouri Health System Site Number : 8400016
Columbia, Missouri, United States
Nebraska Medical Research Institute Site Number : 8400007
Papillion, Nebraska, United States
Change From Baseline to Week 24 in Opacification of Sinuses Assessed by Computed Tomography (CT) Scan Using the Lund Mackay (LMK) Score in Dupilumab Group
The CT scan LMK staging system represented the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus on each side). The extent of mucosal opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the ostiomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is therefore 12 per side; total score ranges from 0 (normal) to 24 (more opacified), corresponding to the sum of all sinuses and the ostiomeatal unit. Higher score indicated worse outcome. Baseline was defined as the last available value up to randomization date and prior to the first dose of study medication.
Time frame: Baseline (Day 1) and Week 24
Change From Baseline to Week 24 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score
The CT scan LMK staging system represented the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus on each side). The extent of mucosal opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the ostiomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is therefore 12 per side; total score ranges from 0 (normal) to 24 (more opacified), corresponding to the sum of all sinuses and the ostiomeatal unit. Higher score indicated worse outcome. Baseline was defined as the last available value up to randomization date and prior to the first dose of study medication.
Time frame: Baseline (Day 1) and Week 24
Change From Baseline to Week 24 in Sinus Total Symptom Score (sTSS)
The sTSS is a composite score derived from the following individual items: nasal congestion (NC), anterior/posterior rhinorrhea, and facial pain/pressure. Each of the individual items were scored from 0 (no symptoms) to 3 (severe symptoms). The total score ranges from 0 to 9 and consists of the sum of NC, the averaged rhinorrhea item scores, and facial pain/pressure scores. Higher scores on sTSS indicated greater overall symptom severity. Baseline was defined as the last available value up to randomization date and prior to the first dose of study medication.
Time frame: Baseline (Day 1) and Week 24
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs (TESAEs), and TEAEs Leading to Treatment Discontinuation
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were AEs that developed, worsened or became serious during the treatment-emergent period. A SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
Time frame: From the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days
Serum Concentration of Dupilumab Over Time
Blood samples were collected at the specified timepoints to evaluate serum concentration of dupilumab.
Time frame: Baseline (Day 1) and Weeks 12, 24 and 52
Number of Participants With Antidrug Antibody (ADA) Response to Dupilumab and Positive Neutralizing Antibody (Nab)
Plasma samples were collected to evaluate antibodies to dupilumab. Pre-existing immunoreactivity was defined as an ADA positive response in the assay at baseline with all post first dose ADA results negative, OR an ADA positive response at baseline with all post first dose ADA responses less than 4-fold over baseline titer levels. Treatment-emergent ADA responses were defined as a positive response in the ADA assay post first dose, when baseline results were negative or missing. Treatment-boosted response was defined as an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive. Samples positive in the ADA assay were further characterized for the presence of NAbs.
Time frame: Baseline (Day 1) and up to Week 52
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Optimed Research, LTD Site Number : 8400017
Columbus, Ohio, United States
Vital Prospects Clinical Research Institute, P.C. Site Number : 8400004
Tulsa, Oklahoma, United States
Essential Medical Research, LLC Site Number : 8400014
Tulsa, Oklahoma, United States
Pharmaceutical Research & Consulting, Inc. Site Number : 8400006
Dallas, Texas, United States
Alamo ENT Associates Site Number : 8400021
San Antonio, Texas, United States
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