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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02898454




Registration number
NCT02898454
Ethics application status
Date submitted
8/09/2016
Date registered
13/09/2016
Date last updated
23/10/2019

Titles & IDs
Public title
Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps
Scientific title
A Randomized, Double-blind, 52-week, Placebo Controlled Efficacy and Safety Study of Dupilumab, in Patients With Bilateral Nasal Polyposis on a Background Therapy With Intranasal Corticosteroids
Secondary ID [1] 0 0
2015-001314-10
Secondary ID [2] 0 0
EFC14280
Universal Trial Number (UTN)
Trial acronym
SINUS-52
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP) 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dupilumab SAR231893 (REGN668)
Treatment: Drugs - Placebo
Treatment: Drugs - Mometasone furoate nasal spray

Experimental: Dupilumab 300 mg q2w - Dupilumab 300 mg subcutaneous (SC) injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.

Experimental: Dupilumab 300 mg q2w then q4w - Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 and then 300 mg q4w until Week 52 added to background therapy of intranasal MFNS at stable dose. After Week 24, Dupilumab administration was alternated with matched placebo injection every other week up to Week 50.

Placebo Comparator: Placebo - Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.


Treatment: Drugs: Dupilumab SAR231893 (REGN668)
Pharmaceutical form: Solution
Route of administration: Subcutaneous

Treatment: Drugs: Placebo
Pharmaceutical form: Solution
Route of administration: Subcutaneous

Treatment: Drugs: Mometasone furoate nasal spray
Pharmaceutical form: Suspension
Route of administration: Intranasal

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score - NC symptom severity was assessed by the participants on a daily basis from visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Least squares (LS) means and standard error (SE) were obtained from Analysis of covariance (ANCOVA) model described in Statistical Analysis Overview. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [1] 0 0
Baseline, Week 24
Primary outcome [2] 0 0
Change From Baseline at Week 24 in Nasal Polyp Score - NPS: sum of right, left nostril scores, evaluated by nasal endoscopy. For each nostril, NPS was graded based on polyp size from 0 = no polyps to 4 = large polyps causing complete obstruction of inferior nasal cavity; lower score = smaller sized polyps. Total NPS: sum of right and left nostril scores, ranges from 0 (no polyps) to 8 (large polyps), higher score = more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay (LMK) Score - The LMK scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score was the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. NOTE: For Japan regulatory submission only, this endpoint is not included as a secondary outcome measure and is instead one of the co-primary outcome measures. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Change From Baseline at Week 24 in Total Symptom Score (TSS) - The TSS was the sum of participant-assessed nasal symptom scores for NC/obstruction, decreased/loss of sense of smell, and rhinorrhea (anterior/posterior nasal discharge), each accessed on 0-3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). Total score ranged from 0 (no symptoms) to 9 (severe symptoms). Higher score indicated more severe symptoms. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
Change From Baseline at Week 24 in the University of Pennsylvania Smell Identification Test (UPSIT) Score - The UPSIT was a 40-item test to measure the individual's ability to detect odors. Total score ranges from 0 (anosmia) to 40 (normal sense of smell), lower score indicated severe smell loss. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
Change From Baseline at Week 24 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily - The severity of decreased/loss of sense of smell was reported by the participants using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms), higher score indicated more severe symptoms. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Change From Baseline at Week 24 in 22-item Sino-nasal Outcome Test (SNOT-22) Scores - The SNOT-22 is a validated questionnaire was used to assess the impact of chronic rhinosinusitis phenotype with nasal polyps (CRSwNP) on health-related quality of life (HRQoL). It is a 22 item questionnaire with each item assigned a score ranging from 0 (no problem) to 5 (problem as bad as it can be). The total score may range from 0 (no disease) to 110 (worst disease), lower scores representing better health related quality of life. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
Change From Baseline at Week 52 in Nasal Polyp Score - NPS was the sum of right and left nostril scores, as evaluated by means of nasal endoscopy. For each nostril, NPS was graded based on polyp size from 0 to 4 (0 = no polyps to 4 = large polyps causing complete obstruction of the inferior nasal cavity), with a lower score indicating smaller-sized polyps. Total NPS was the sum of right and left nostril scores and ranges from 0 (no polyp) to 8 (large polyp), with highest score representing more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. Data were analyzed using a hybrid method of the WOCF and MI. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview.
Timepoint [6] 0 0
Baseline, Week 52
Secondary outcome [7] 0 0
Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score - NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview.
Timepoint [7] 0 0
Baseline, Week 52
Secondary outcome [8] 0 0
Change From Baseline at Week 52 in 22-item Sino-nasal Outcome Test Scores - The SNOT-22 is a validated questionnaire that was used to assess the impact of CRSwNP on HRQoL. It is a 22 item questionnaire with each item assigned a score ranging from 0 (no problem) to 5 (problem as bad as it can be). The total score may range from 0 (no disease) to 110 (worst disease), lower scores representing better health related quality of life. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview.
Timepoint [8] 0 0
Baseline, Week 52
Secondary outcome [9] 0 0
Rescue Treatment Use: Estimate of Percentage of Participants With Greater Than or Equal to (>=) 1 Event by Week 52 Obtained Using Kaplan-Meier Method - Rescue treatment was defined as usage of systemic corticosteroids (SCS) or NP surgery (actual or planned) during the treatment period. Rescue treatment included:
SCS: betamethasone, deflazacort, dexamethasone, dexamethasone sodium phosphate, hydrocortisone, meprednisone, methylprednisolone, methylprednisolone sodium succinate, prednisolone, prednisolone sodium succinate, prednisone, stelamin, triamcinolone, and triamcinolone acetonide.
Sino-nasal surgery for nasal polyps when there was worsening of signs and/or symptoms during the study.
Estimate of percentage of participants with event by Week 52 was obtained using Kaplan-Meier method.
Timepoint [9] 0 0
Baseline up to 52 weeks
Secondary outcome [10] 0 0
Change From Baseline at Week 52 in Total Symptom Score - The TSS was the sum of participant-assessed nasal symptom scores for NC/obstruction, decreased/loss of sense of smell, and rhinorrhea (anterior/posterior nasal discharge), each accessed on 0-3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). Total score ranged from 0 (no symptoms) to 9 (severe symptoms). Higher score indicated more severe symptoms. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.
Timepoint [10] 0 0
Baseline, Week 52
Secondary outcome [11] 0 0
Change From Baseline at Week 52 in the University of Pennsylvania Smell Identification Test Score - The UPSIT was a 40-item test to measure the individual's ability to detect odors. Total score ranges from 0 (anosmia) to 40 (normal sense of smell), lower score indicated severe smell loss. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.
Timepoint [11] 0 0
Baseline, Week 52
Secondary outcome [12] 0 0
Change From Baseline at Week 52 in Severity of Decreased/Loss of Smell - The severity of decreased/loss of sense of smell was reported by the participants using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms), higher score indicated more severe symptoms. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.
Timepoint [12] 0 0
Baseline, Week 52
Secondary outcome [13] 0 0
Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund-Mackay Score - The LMK scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score was the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.
Timepoint [13] 0 0
Baseline, Week 52
Secondary outcome [14] 0 0
Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis - The VAS for rhinosinusitis was used to evaluate the total disease severity. The participants were asked to indicate on a 10 centimeters VAS the answer to the question, "How troublesome are your symptoms of your rhinosinusitis?" The range of the VAS was from 0 (not troublesome) to 10 (worse thinkable troublesome), where higher score indicated worse thinkable troublesome. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [14] 0 0
Baseline, Week 24
Secondary outcome [15] 0 0
Change From Baseline at Week 52 in Visual Analogue Scale for Rhinosinusitis - The VAS for rhinosinusitis was used to evaluate the total disease severity. The participants were asked to indicate on a 10 centimeters VAS the answer to the question, "How troublesome are your symptoms of your rhinosinusitis?" The range of the VAS was from 0 (not troublesome) to 10 (worse thinkable troublesome), where higher score indicated worse thinkable troublesome. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.
Timepoint [15] 0 0
Baseline, Week 52
Secondary outcome [16] 0 0
Change From Baseline at Week 24 in Nasal Peak Inspiratory Flow (NPIF) - NPIF evaluation represented a physiologic measure of the air flow through both nasal cavities during forced inspiration expressed in liters per minute. Higher NPIF values were indicative of better nasal air flow. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [16] 0 0
Baseline, Week 24
Secondary outcome [17] 0 0
Change From Baseline at Week 24 in Rhinorrhea Daily Symptom Score - Rhinorrhea was reported by the participants using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms), where higher scores indicated more severe symptoms. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [17] 0 0
Baseline, Week 24
Secondary outcome [18] 0 0
Change From Baseline at Week 52 in Rhinorrhea Daily Symptom Score - Rhinorrhea was reported by the participants using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms), where higher scores indicated more severe symptoms. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.
Timepoint [18] 0 0
Baseline, Week 52
Secondary outcome [19] 0 0
Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period - SCS included: betamethasone, deflazacort, dexamethasone, dexamethasone sodium phosphate, hydrocortisone, meprednisone, methylprednisolone, methylprednisolone sodium succinate, prednisolone, prednisolone sodium succinate, prednisone, stelamin, triamcinolone, and triamcinolone acetonide. For every participant, the total dose was calculated as (prescribed total daily dose*duration of SCS use). Then, mean of the total dose of 64 participants (placebo group), 17 participants (dupilumab 300 mg q2w then q4w) and 22 participants (dupilumab 300 mg q2w) was derived.
Timepoint [19] 0 0
Baseline to Week 52
Secondary outcome [20] 0 0
Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant - Rescue treatment was defined as usage of SCS or NP surgery (actual or planned) during the treatment period. SCS Rescue intake duration was defined as the duration (in days) from start of SCS rescue medication till the end of SCS rescue treatment.
Timepoint [20] 0 0
Baseline to Week 52
Secondary outcome [21] 0 0
Changed From Baseline at Week 24 in Forced Expiratory Volume in 1 Second (FEV1) for Participants With Asthma - FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [21] 0 0
Baseline, Week 24
Secondary outcome [22] 0 0
Change From Baseline at Week 52 in Forced Expiratory Volume in 1 Second for Participants With Asthma - FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, prior surgery history, and regions as covariates.
Timepoint [22] 0 0
Baseline, Week 52
Secondary outcome [23] 0 0
Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) for Participants With Asthma - ACQ-6 had 6 questions which assessed the most common asthma symptoms (woken by asthma, symptoms on waking, activity limitation, shortness of breath, wheezing, puffs/inhalations use). Participants were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale ranged from 0 = no impairment to 6 = maximum impairment. The ACQ-6 score was the mean of the scores of all 6 questions and therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), with higher scores indicated lower asthma control. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment, asthma status, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [23] 0 0
Baseline, Week 24
Secondary outcome [24] 0 0
Change From Baseline at Week 52 in Asthma Control Questionnaire-6 for Participants With Asthma - ACQ-6 had 6 questions which assessed the most common asthma symptoms (woken by asthma, symptoms on waking, activity limitation, shortness of breath, wheezing, puffs/inhalations use). Participants were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale ranged from 0 = no impairment to 6 = maximum impairment. The ACQ-6 score was the mean of the scores of all 6 questions and therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), with higher scores indicated lower asthma control. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment, asthma status, prior surgery history, and regions as covariates.
Timepoint [24] 0 0
Baseline, Week 52
Secondary outcome [25] 0 0
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma - NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [25] 0 0
Baseline, Week 24
Secondary outcome [26] 0 0
Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma - NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates.
Timepoint [26] 0 0
Baseline, Week 52
Secondary outcome [27] 0 0
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery - NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [27] 0 0
Baseline, Week 24
Secondary outcome [28] 0 0
Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery - NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, and regions as covariates.
Timepoint [28] 0 0
Baseline, Week 52
Secondary outcome [29] 0 0
Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Asthma - NPS was the sum of right and left nostril scores, as evaluated by means of nasal endoscopy. For each nostril, NPS was graded from 0 to 4 (0 = no polyps to 4 = large polyps causing complete obstruction of the inferior nasal cavity), with a lower score indicating smaller-sized polyps. Total NPS was the sum of right and left nostril scores and ranges from 0 (no polyp) to 8 (large polyp), with highest score representing more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. Data were analyzed using a hybrid method of the WOCF and MI. LS mean and SE were obtained from ANCOVA model. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [29] 0 0
Baseline, Week 24
Secondary outcome [30] 0 0
Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Asthma - NPS was the sum of right and left nostril scores, as evaluated by means of nasal endoscopy. For each nostril, NPS was graded from 0 to 4 (0 = no polyps to 4 = large polyps causing complete obstruction of the inferior nasal cavity), with a lower score indicating smaller-sized polyps. Total NPS was the sum of right and left nostril scores and ranges from 0 (no polyp) to 8 (large polyp), with highest score representing more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. Data were analyzed using a hybrid method of the WOCF and MI. LS mean and SE were obtained from ANCOVA model.
Timepoint [30] 0 0
Baseline, Week 52
Secondary outcome [31] 0 0
Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery - NPS was the sum of right and left nostril scores, as evaluated by means of nasal endoscopy. For each nostril, NPS was graded from 0 to 4 (0 = no polyps to 4 = large polyps causing complete obstruction of the inferior nasal cavity), with a lower score indicating smaller-sized polyps. Total NPS was the sum of right and left nostril scores and ranges from 0 (no polyp) to 8 (large polyp), with highest score representing more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. Data were analyzed using a hybrid method of the WOCF and MI. LS mean and SE were obtained from ANCOVA model. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [31] 0 0
Baseline, Week 24
Secondary outcome [32] 0 0
Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery - NPS was the sum of right and left nostril scores, as evaluated by means of nasal endoscopy. For each nostril, NPS was graded from 0 to 4 (0 = no polyps to 4 = large polyps causing complete obstruction of the inferior nasal cavity), with a lower score indicating smaller-sized polyps. Total NPS was the sum of right and left nostril scores and ranges from 0 (no polyp) to 8 (large polyp), with highest score representing more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. Data were analyzed using a hybrid method of the WOCF and MI. LS mean and SE were obtained from ANCOVA model.
Timepoint [32] 0 0
Baseline, Week 52
Secondary outcome [33] 0 0
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma - The LMK scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score was the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [33] 0 0
Baseline, Week 24
Secondary outcome [34] 0 0
Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma - The LMK scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score was the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.
Timepoint [34] 0 0
Baseline, Week 52
Secondary outcome [35] 0 0
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery - The LMK scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score was the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [35] 0 0
Baseline, Week 24
Secondary outcome [36] 0 0
Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery - The LMK scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score was the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, and regions as covariates.
Timepoint [36] 0 0
Baseline, Week 52
Secondary outcome [37] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation - An Adverse Event (AE) was defined as any untoward medical occurrence that did not necessarily have to have a causal relationship with the study treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during TEAE period which was defined as the period from the time of first dose of drug until 84 days following the last administration of drug. SAE was defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.
Timepoint [37] 0 0
Baseline up to 84 days after last dose of study drug (up to 64 weeks)
Secondary outcome [38] 0 0
Change From Baseline at Week 24 in European Quality of Life 5 Dimension Scale (EQ-5D) Visual Analog Scale Score - The EQ-5D was a standardized HRQoL questionnaire consisting of EQ-5D descriptive system and EQ VAS. The EQ-5D descriptive system comprised of 5 dimensions: mobility, selfcare, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. EQ VAS recorded the participant's self-rated health on a vertical VAS that allowed them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable). All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Timepoint [38] 0 0
Baseline, Week 24
Secondary outcome [39] 0 0
Change From Baseline at Week 52 in European Quality of Life 5 Dimension Scale Visual Analog Scale Score - The EQ-5D was a standardized HRQoL questionnaire consisting of EQ-5D descriptive system and EQ VAS. The EQ-5D descriptive system comprised of 5 dimensions: mobility, selfcare, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. EQ VAS recorded the participant's self-rated health on a vertical VAS that allowed them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable).
Timepoint [39] 0 0
Baseline, Week 52
Secondary outcome [40] 0 0
Functional Dupilumab Concentration in Serum
Timepoint [40] 0 0
Baseline, Week 2, Week 4, Week 16, Week 24, Week 40, End of treatment (Week 52), End of study (Week 64)
Secondary outcome [41] 0 0
Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies Response (ADA) - ADA response were categorized as: treatment emergent and treatment boosted response. 1) Treatment emergent was defined as a positive response in the ADA assay post first dose, when baseline results are negative or missing. 2) Treatment boosted was defined as: an ADA positive response in the assay post first dose that is greater-than or equal to 4-fold over baseline titer levels, when baseline results are positive.
Timepoint [41] 0 0
Baseline to Week 52

Eligibility
Key inclusion criteria
Inclusion criteria :

- Participants with bilateral sino-nasal polyposis that despite prior treatment with SCS
anytime within the past 2 years; and/or had a medical contraindication/intolerance to
SCS; and/or had prior surgery for NP at the screening visit, had:

- An endoscopic bilateral NPS at Visit 1 (V1) 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 NC/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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Participants <18 years of age.

- Participant who had been previously treated in dupilumab studies.

- Participant who had 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 was longer.

- Any experimental monoclonal antibody within 5 half-lives or within 6 months
before V1 if the half-life was unknown.

- Anti-immunoglobulin E therapy (omalizumab) within 130 days prior to V1.

- Participants who received leukotriene antagonists/modifiers at V1 unless they
were 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.

- Participants who underwent any and/or sinus surgery (including polypectomy) within 6
months before V1.

- Participants who had a sino-nasal or sinus surgery changing the lateral wall structure
of the nose making impossible the evaluation of NPS.

- Participants 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.

- Participants with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood
boil etc.).

- Participants with forced expiratory volume 50% or less (of predicted normal).

- Participants who received concomitant treatment prohibited in the study.

- Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit.

- 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 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.

The above information was not intended to contain all considerations relevant to a
Participant's potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360002 - Clayton
Recruitment hospital [2] 0 0
Investigational Site Number 0360004 - Herston
Recruitment hospital [3] 0 0
Investigational Site Number 0360005 - Murdoch
Recruitment hospital [4] 0 0
Investigational Site Number 0360001 - Parkville
Recruitment hospital [5] 0 0
Investigational Site Number 0360003 - Prahran
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
3004 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Argentina
State/province [14] 0 0
Buenos Aires
Country [15] 0 0
Argentina
State/province [15] 0 0
Caba
Country [16] 0 0
Argentina
State/province [16] 0 0
Mendoza
Country [17] 0 0
Argentina
State/province [17] 0 0
Rosario
Country [18] 0 0
Argentina
State/province [18] 0 0
San Miguel De Tucumán
Country [19] 0 0
Belgium
State/province [19] 0 0
Bruxelles
Country [20] 0 0
Belgium
State/province [20] 0 0
Gent
Country [21] 0 0
Belgium
State/province [21] 0 0
Leuven
Country [22] 0 0
Canada
State/province [22] 0 0
Kingston
Country [23] 0 0
Canada
State/province [23] 0 0
Montreal
Country [24] 0 0
Canada
State/province [24] 0 0
Ottawa
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
Canada
State/province [26] 0 0
Trois-Rivieres
Country [27] 0 0
Canada
State/province [27] 0 0
Vancouver
Country [28] 0 0
Chile
State/province [28] 0 0
Quillota
Country [29] 0 0
Chile
State/province [29] 0 0
San Fernando
Country [30] 0 0
Chile
State/province [30] 0 0
Santiago
Country [31] 0 0
Chile
State/province [31] 0 0
Talca
Country [32] 0 0
Chile
State/province [32] 0 0
Viña Del Mar
Country [33] 0 0
Israel
State/province [33] 0 0
Hadera
Country [34] 0 0
Israel
State/province [34] 0 0
Nahariya
Country [35] 0 0
Israel
State/province [35] 0 0
Petah-Tikva
Country [36] 0 0
Israel
State/province [36] 0 0
Rehovot
Country [37] 0 0
Israel
State/province [37] 0 0
Tel Hashomer
Country [38] 0 0
Japan
State/province [38] 0 0
Bunkyo-Ku
Country [39] 0 0
Japan
State/province [39] 0 0
Chiyoda-Ku
Country [40] 0 0
Japan
State/province [40] 0 0
Fukuoka-Shi
Country [41] 0 0
Japan
State/province [41] 0 0
Hirakata-Shi
Country [42] 0 0
Japan
State/province [42] 0 0
Hiroshima-Shi
Country [43] 0 0
Japan
State/province [43] 0 0
Iida-Shi
Country [44] 0 0
Japan
State/province [44] 0 0
Inzai-Shi
Country [45] 0 0
Japan
State/province [45] 0 0
Itabashi-Ku
Country [46] 0 0
Japan
State/province [46] 0 0
Izumisano-Shi
Country [47] 0 0
Japan
State/province [47] 0 0
Kawasaki-Shi
Country [48] 0 0
Japan
State/province [48] 0 0
Kitakyushu-Shi
Country [49] 0 0
Japan
State/province [49] 0 0
Kumamoto-Shi
Country [50] 0 0
Japan
State/province [50] 0 0
Kyoto-Shi
Country [51] 0 0
Japan
State/province [51] 0 0
Meguro-Ku
Country [52] 0 0
Japan
State/province [52] 0 0
Moriguchi-Shi
Country [53] 0 0
Japan
State/province [53] 0 0
Okayama-Shi
Country [54] 0 0
Japan
State/province [54] 0 0
Osaka-Shi
Country [55] 0 0
Japan
State/province [55] 0 0
Ota-Ku
Country [56] 0 0
Japan
State/province [56] 0 0
Sendai-Shi
Country [57] 0 0
Japan
State/province [57] 0 0
Shimonoseki-Shi
Country [58] 0 0
Japan
State/province [58] 0 0
Shinagawa-Ku
Country [59] 0 0
Japan
State/province [59] 0 0
Shinjyuku-Ku
Country [60] 0 0
Japan
State/province [60] 0 0
Takatsuki-Shi
Country [61] 0 0
Japan
State/province [61] 0 0
Yoshida-Gun
Country [62] 0 0
Mexico
State/province [62] 0 0
Chihuahua
Country [63] 0 0
Mexico
State/province [63] 0 0
Durango
Country [64] 0 0
Mexico
State/province [64] 0 0
Guadalajara
Country [65] 0 0
Mexico
State/province [65] 0 0
Monterrey
Country [66] 0 0
Portugal
State/province [66] 0 0
Aveiro
Country [67] 0 0
Portugal
State/province [67] 0 0
Guimarães
Country [68] 0 0
Portugal
State/province [68] 0 0
Lisboa
Country [69] 0 0
Portugal
State/province [69] 0 0
Matosinhos
Country [70] 0 0
Portugal
State/province [70] 0 0
Porto
Country [71] 0 0
Portugal
State/province [71] 0 0
Viana Do Castelo
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Moscow
Country [73] 0 0
Russian Federation
State/province [73] 0 0
Odintsovo
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Saint-Petersburg
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Stavropol
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Yaroslavl
Country [77] 0 0
Spain
State/province [77] 0 0
Barcelona
Country [78] 0 0
Spain
State/province [78] 0 0
Jerez De La Frontera
Country [79] 0 0
Spain
State/province [79] 0 0
Madrid
Country [80] 0 0
Spain
State/province [80] 0 0
Sevilla
Country [81] 0 0
Spain
State/province [81] 0 0
Valencia
Country [82] 0 0
Sweden
State/province [82] 0 0
Lund
Country [83] 0 0
Sweden
State/province [83] 0 0
Stockholm
Country [84] 0 0
Turkey
State/province [84] 0 0
Ankara
Country [85] 0 0
Turkey
State/province [85] 0 0
Bursa
Country [86] 0 0
Turkey
State/province [86] 0 0
Istanbul
Country [87] 0 0
Turkey
State/province [87] 0 0
Izmir
Country [88] 0 0
Turkey
State/province [88] 0 0
Rize

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

To evaluate the efficacy of dupilumab 300 mg every 2 weeks (q2w) compared to placebo on a
background of mometasone furoate nasal spray (MFNS) in reducing nasal congestion
(NC)/obstruction severity and endoscopic nasal polyp score (NPS) in participants with
bilateral nasal polyps (NP). In addition for Japanese participants, reduction in computed
tomography (CT) scan opacification of the sinuses was a co-primary objective.

Secondary Objectives:

- To evaluate the efficacy of dupilumab in improving total symptoms score.

- 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 Japanese participants).

- To evaluate ability of dupilumab in reducing proportion of participants who required
treatment with systemic corticosteroids (SCS) or surgery for NP.

- To evaluate the effect of dupilumab on participant reported outcomes and health related
quality of life.

- To evaluate the efficacy of dupilumab 300 mg q2w up to Week 52.

- To evaluate the efficacy of dupilumab 300 mg q2w up to Week 24 followed by 300 mg every
4 weeks (q4w) up to Week 52.

- To evaluate the effect of dupilumab in the subgroups of participants with prior surgery
and comorbid asthma including non-steroid anti-inflammatory drug exacerbated respiratory
disease.

- To evaluate the safety of dupilumab in participants with bilateral NP.

- To evaluate functional dupilumab concentrations (systemic exposure) and incidence of
treatment emergent anti-drug antibodies.
Trial website
https://clinicaltrials.gov/show/NCT02898454
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications