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Trial details imported from ClinicalTrials.gov

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

2015-001314-10

Secondary ID [2]

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)

Condition category

Condition code

Infection

Other infectious diseases

Respiratory

Other respiratory disorders / diseases

Other

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]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score

Assessment method [1]

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]

Baseline, Week 24

Primary outcome [2]

Change From Baseline at Week 24 in Nasal Polyp Score

Assessment method [2]

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]

Baseline, Week 24

Secondary outcome [1]

Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay (LMK) Score

Assessment method [1]

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]

Baseline, Week 24

Secondary outcome [2]

Change From Baseline at Week 24 in Total Symptom Score (TSS)

Assessment method [2]

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]

Baseline, Week 24

Secondary outcome [3]

Change From Baseline at Week 24 in the University of Pennsylvania Smell Identification Test (UPSIT) Score

Assessment method [3]

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]

Baseline, Week 24

Secondary outcome [4]

Change From Baseline at Week 24 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily

Assessment method [4]

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]

Baseline, Week 24

Secondary outcome [5]

Change From Baseline at Week 24 in 22-item Sino-nasal Outcome Test (SNOT-22) Scores

Assessment method [5]

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]

Baseline, Week 24

Secondary outcome [6]

Change From Baseline at Week 52 in Nasal Polyp Score

Assessment method [6]

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]

Baseline, Week 52

Secondary outcome [7]

Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score

Assessment method [7]

Timepoint [7]

Baseline, Week 52

Secondary outcome [8]

Change From Baseline at Week 52 in 22-item Sino-nasal Outcome Test Scores

Assessment method [8]

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]

Baseline, Week 52

Secondary outcome [9]

Rescue Treatment Use: Estimate of Percentage of Participants With Greater Than or Equal to (>=) 1 Event by Week 52 Obtained Using Kaplan-Meier Method

Assessment method [9]

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]

Baseline up to 52 weeks

Secondary outcome [10]

Change From Baseline at Week 52 in Total Symptom Score

Assessment method [10]

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]

Baseline, Week 52

Secondary outcome [11]

Change From Baseline at Week 52 in the University of Pennsylvania Smell Identification Test Score

Assessment method [11]

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]

Baseline, Week 52

Secondary outcome [12]

Change From Baseline at Week 52 in Severity of Decreased/Loss of Smell

Assessment method [12]

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]

Baseline, Week 52

Secondary outcome [13]

Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund-Mackay Score

Assessment method [13]

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]

Baseline, Week 52

Secondary outcome [14]

Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis

Assessment method [14]

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]

Baseline, Week 24

Secondary outcome [15]

Change From Baseline at Week 52 in Visual Analogue Scale for Rhinosinusitis

Assessment method [15]

Timepoint [15]

Baseline, Week 52

Secondary outcome [16]

Change From Baseline at Week 24 in Nasal Peak Inspiratory Flow (NPIF)

Assessment method [16]

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]

Baseline, Week 24

Secondary outcome [17]

Change From Baseline at Week 24 in Rhinorrhea Daily Symptom Score

Assessment method [17]

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]

Baseline, Week 24

Secondary outcome [18]

Change From Baseline at Week 52 in Rhinorrhea Daily Symptom Score

Assessment method [18]

Timepoint [18]

Baseline, Week 52

Secondary outcome [19]

Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period

Assessment method [19]

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]

Baseline to Week 52

Secondary outcome [20]

Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant

Assessment method [20]

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]

Baseline to Week 52

Secondary outcome [21]

Changed From Baseline at Week 24 in Forced Expiratory Volume in 1 Second (FEV1) for Participants With Asthma

Assessment method [21]

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]

Baseline, Week 24

Secondary outcome [22]

Change From Baseline at Week 52 in Forced Expiratory Volume in 1 Second for Participants With Asthma

Assessment method [22]

Timepoint [22]

Baseline, Week 52

Secondary outcome [23]

Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) for Participants With Asthma

Assessment method [23]

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]

Baseline, Week 24

Secondary outcome [24]

Change From Baseline at Week 52 in Asthma Control Questionnaire-6 for Participants With Asthma

Assessment method [24]

Timepoint [24]

Baseline, Week 52

Secondary outcome [25]

Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma

Assessment method [25]

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]

Baseline, Week 24

Secondary outcome [26]

Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma

Assessment method [26]

Timepoint [26]

Baseline, Week 52

Secondary outcome [27]

Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery

Assessment method [27]

Timepoint [27]

Baseline, Week 24

Secondary outcome [28]

Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery

Assessment method [28]

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]

Baseline, Week 52

Secondary outcome [29]

Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Asthma

Assessment method [29]

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]

Baseline, Week 24

Secondary outcome [30]

Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Asthma

Assessment method [30]

Timepoint [30]

Baseline, Week 52

Secondary outcome [31]

Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery

Assessment method [31]

Timepoint [31]

Baseline, Week 24

Secondary outcome [32]

Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery

Assessment method [32]

Timepoint [32]

Baseline, Week 52

Secondary outcome [33]

Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma

Assessment method [33]

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]

Baseline, Week 24

Secondary outcome [34]

Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma

Assessment method [34]

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]

Baseline, Week 52

Secondary outcome [35]

Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery

Assessment method [35]

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]

Baseline, Week 24

Secondary outcome [36]

Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery

Assessment method [36]

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]

Baseline, Week 52

Secondary outcome [37]

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation

Assessment method [37]

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]

Baseline up to 84 days after last dose of study drug (up to 64 weeks)

Secondary outcome [38]

Change From Baseline at Week 24 in European Quality of Life 5 Dimension Scale (EQ-5D) Visual Analog Scale Score

Assessment method [38]

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]

Baseline, Week 24

Secondary outcome [39]

Change From Baseline at Week 52 in European Quality of Life 5 Dimension Scale Visual Analog Scale Score

Assessment method [39]

Timepoint [39]

Baseline, Week 52

Secondary outcome [40]

Functional Dupilumab Concentration in Serum

Assessment method [40]

Timepoint [40]

Baseline, Week 2, Week 4, Week 16, Week 24, Week 40, End of treatment (Week 52), End of study (Week 64)

Secondary outcome [41]

Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies Response (ADA)

Assessment method [41]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

28/11/2016

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

16/11/2018

Sample size

Target

Accrual to date

Final

448

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Investigational Site Number 0360002 - Clayton

Recruitment hospital [2]

Investigational Site Number 0360004 - Herston

Recruitment hospital [3]

Investigational Site Number 0360005 - Murdoch

Recruitment hospital [4]

Investigational Site Number 0360001 - Parkville

Recruitment hospital [5]

Investigational Site Number 0360003 - Prahran

Recruitment postcode(s) [1]

3168 - Clayton

Recruitment postcode(s) [2]

4029 - Herston

Recruitment postcode(s) [3]

6150 - Murdoch

Recruitment postcode(s) [4]

3050 - Parkville

Recruitment postcode(s) [5]

3004 - Prahran

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Alabama

Country [2]

United States of America

State/province [2]

California

Country [3]

United States of America

State/province [3]

Colorado

Country [4]

United States of America

State/province [4]

Connecticut

Country [5]

United States of America

State/province [5]

Kentucky

Country [6]

United States of America

State/province [6]

Massachusetts

Country [7]

United States of America

State/province [7]

Missouri

Country [8]

United States of America

State/province [8]

New York

Country [9]

United States of America

State/province [9]

North Carolina

Country [10]

United States of America

State/province [10]

Pennsylvania

Country [11]

United States of America

State/province [11]

Utah

Country [12]

United States of America

State/province [12]

Washington

Country [13]

United States of America

State/province [13]

Wisconsin

Country [14]

Argentina

State/province [14]

Buenos Aires

Country [15]

Argentina

State/province [15]

Caba

Country [16]

Argentina

State/province [16]

Mendoza

Country [17]

Argentina

State/province [17]

Rosario

Country [18]

Argentina

State/province [18]

San Miguel De Tucumán

Country [19]

Belgium

State/province [19]

Bruxelles

Country [20]

Belgium

State/province [20]

Gent

Country [21]

Belgium

State/province [21]

Leuven

Country [22]

Canada

State/province [22]

Kingston

Country [23]

Canada

State/province [23]

Montreal

Country [24]

Canada

State/province [24]

Ottawa

Country [25]

Canada

State/province [25]

Quebec

Country [26]

Canada

State/province [26]

Trois-Rivieres

Country [27]

Canada

State/province [27]

Vancouver

Country [28]

Chile

State/province [28]

Quillota

Country [29]

Chile

State/province [29]

San Fernando

Country [30]

Chile

State/province [30]

Santiago

Country [31]

Chile

State/province [31]

Talca

Country [32]

Chile

State/province [32]

Viña Del Mar

Country [33]

Israel

State/province [33]

Hadera

Country [34]

Israel

State/province [34]

Nahariya

Country [35]

Israel

State/province [35]

Petah-Tikva

Country [36]

Israel

State/province [36]

Rehovot

Country [37]

Israel

State/province [37]

Tel Hashomer

Country [38]

Japan

State/province [38]

Bunkyo-Ku

Country [39]

Japan

State/province [39]

Chiyoda-Ku

Country [40]

Japan

State/province [40]

Fukuoka-Shi

Country [41]

Japan

State/province [41]

Hirakata-Shi

Country [42]

Japan

State/province [42]

Hiroshima-Shi

Country [43]

Japan

State/province [43]

Iida-Shi

Country [44]

Japan

State/province [44]

Inzai-Shi

Country [45]

Japan

State/province [45]

Itabashi-Ku

Country [46]

Japan

State/province [46]

Izumisano-Shi

Country [47]

Japan

State/province [47]

Kawasaki-Shi

Country [48]

Japan

State/province [48]

Kitakyushu-Shi

Country [49]

Japan

State/province [49]

Kumamoto-Shi

Country [50]

Japan

State/province [50]

Kyoto-Shi

Country [51]

Japan

State/province [51]

Meguro-Ku

Country [52]

Japan

State/province [52]

Moriguchi-Shi

Country [53]

Japan

State/province [53]

Okayama-Shi

Country [54]

Japan

State/province [54]

Osaka-Shi

Country [55]

Japan

State/province [55]

Ota-Ku

Country [56]

Japan

State/province [56]

Sendai-Shi

Country [57]

Japan

State/province [57]

Shimonoseki-Shi

Country [58]

Japan

State/province [58]

Shinagawa-Ku

Country [59]

Japan

State/province [59]

Shinjyuku-Ku

Country [60]

Japan

State/province [60]

Takatsuki-Shi

Country [61]

Japan

State/province [61]

Yoshida-Gun

Country [62]

Mexico

State/province [62]

Chihuahua

Country [63]

Mexico

State/province [63]

Durango

Country [64]

Mexico

State/province [64]

Guadalajara

Country [65]

Mexico

State/province [65]

Monterrey

Country [66]

Portugal

State/province [66]

Aveiro

Country [67]

Portugal

State/province [67]

Guimarães

Country [68]

Portugal

State/province [68]

Lisboa

Country [69]

Portugal

State/province [69]

Matosinhos

Country [70]

Portugal

State/province [70]

Porto

Country [71]

Portugal

State/province [71]

Viana Do Castelo

Country [72]

Russian Federation

State/province [72]

Moscow

Country [73]

Russian Federation

State/province [73]

Odintsovo

Country [74]

Russian Federation

State/province [74]

Saint-Petersburg

Country [75]

Russian Federation

State/province [75]

Stavropol

Country [76]

Russian Federation

State/province [76]

Yaroslavl

Country [77]

Spain

State/province [77]

Barcelona

Country [78]

Spain

State/province [78]

Jerez De La Frontera

Country [79]

Spain

State/province [79]

Madrid

Country [80]

Spain

State/province [80]

Sevilla

Country [81]

Spain

State/province [81]

Valencia

Country [82]

Sweden

State/province [82]

Lund

Country [83]

Sweden

State/province [83]

Stockholm

Country [84]

Turkey

State/province [84]

Ankara

Country [85]

Turkey

State/province [85]

Bursa

Country [86]

Turkey

State/province [86]

Istanbul

Country [87]

Turkey

State/province [87]

Izmir

Country [88]

Turkey

State/province [88]

Rize

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

Sanofi

Country

Other collaborator category [1]

Commercial sector/industry

Name [1]

Regeneron Pharmaceuticals

Country [1]

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/study/NCT02898454

Trial related presentations / publications

Peters AT, Soler ZM, Kern RC, Heffler E, Maspero JF, Crampette L, Fujieda S, Lane AP, Zhang H, Nash S, Khan AH, Siddiqui S, Jacob-Nara JA, Rowe P, Deniz Y. Improvement in patient-reported "taste" and association with smell in dupilumab-treated patients with severe chronic rhinosinusitis with nasal polyps from the SINUS-24 and SINUS-52 trials. Clin Exp Allergy. 2022 Sep;52(9):1105-1109. doi: 10.1111/cea.14194. Epub 2022 Jul 12. No abstract available.
Wechsler ME, Klion AD, Paggiaro P, Nair P, Staumont-Salle D, Radwan A, Johnson RR, Kapoor U, Khokhar FA, Daizadeh N, Chen Z, Laws E, Ortiz B, Jacob-Nara JA, Mannent LP, Rowe PJ, Deniz Y. Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2022 Oct;10(10):2695-2709. doi: 10.1016/j.jaip.2022.05.019. Epub 2022 May 28.
Bachert C, Peters AT, Heffler E, Han JK, Olze H, Pfaar O, Chuang CC, Rout R, Attre R, Goga L, Jacob-Nara JA, Rowe PJ, Deniz Y, Chen Z, Kamat S, Siddiqui S. Responder analysis to demonstrate the effect of targeting type 2 inflammatory mechanisms with dupilumab across objective and patient-reported endpoints for patients with severe chronic rhinosinusitis with nasal polyps in the SINUS-24 and SINUS-52 studies. Clin Exp Allergy. 2022 Feb;52(2):244-249. doi: 10.1111/cea.14051. No abstract available.
Lee SE, Hopkins C, Mullol J, Msihid J, Guillemin I, Amin N, Mannent LP, Li Y, Siddiqui S, Chuang CC, Kamat S, Khan AH. Dupilumab improves health related quality of life: Results from the phase 3 SINUS studies. Allergy. 2022 Jul;77(7):2211-2221. doi: 10.1111/all.15222. Epub 2022 Feb 1.
Bachert C, Corren J, Lee SE, Zhang H, Harel S, Cunoosamy D, Khan AH, Jacob-Nara JA, Siddiqui S, Nash S, Rowe PJ, Deniz Y. Dupilumab efficacy and biomarkers in chronic rhinosinusitis with nasal polyps: Association between dupilumab treatment effect on nasal polyp score and biomarkers of type 2 inflammation in patients with chronic rhinosinusitis with nasal polyps in the phase 3 SINUS-24 and SINUS-52 trials. Int Forum Allergy Rhinol. 2022 Sep;12(9):1191-1195. doi: 10.1002/alr.22964. Epub 2022 Jan 31. No abstract available.
Geng B, Bachert C, Busse WW, Gevaert P, Lee SE, Niederman MS, Chen Z, Lu X, Khokhar FA, Kapoor U, Pandit-Abid N, Jacob-Nara JA, Rowe PJ, Deniz Y, Ortiz B. Respiratory Infections and Anti-Infective Medication Use From Phase 3 Dupilumab Respiratory Studies. J Allergy Clin Immunol Pract. 2022 Mar;10(3):732-741. doi: 10.1016/j.jaip.2021.12.006. Epub 2021 Dec 22.
Hellings PW, Peters AT, Chaker AM, Heffler E, Zhang H, Praestgaard A, Nash S, Khan AH, Siddiqui S, Jacob-Nara JA, Rowe PJ, Deniz Y. Rapid and sustained effects of dupilumab in severe chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2022 Jul;12(7):958-962. doi: 10.1002/alr.22944. Epub 2022 Jan 23. No abstract available.
Han JK, Bachert C, Lee SE, Hopkins C, Heffler E, Hellings PW, Peters AT, Kamat S, Whalley D, Qin S, Nelson L, Siddiqui S, Khan AH, Li Y, Mannent LP, Guillemin I, Chuang CC. Estimating Clinically Meaningful Change of Efficacy Outcomes in Inadequately Controlled Chronic Rhinosinusitis with Nasal Polyposis. Laryngoscope. 2022 Feb;132(2):265-271. doi: 10.1002/lary.29888. Epub 2021 Dec 1.
Chuang CC, Guillemin I, Bachert C, Lee SE, Hellings PW, Fokkens WJ, Duverger N, Fan C, Daizadeh N, Amin N, Mannent LP, Khan AH, Kamat S. Dupilumab in CRSwNP: Responder Analysis Using Clinically Meaningful Efficacy Outcome Thresholds. Laryngoscope. 2022 Feb;132(2):259-264. doi: 10.1002/lary.29911. Epub 2021 Nov 24.
Mullol J, Laidlaw TM, Bachert C, Mannent LP, Canonica GW, Han JK, Maspero JF, Picado C, Daizadeh N, Ortiz B, Li Y, Ruddy M, Laws E, Amin N. Efficacy and safety of dupilumab in patients with uncontrolled severe chronic rhinosinusitis with nasal polyps and a clinical diagnosis of NSAID-ERD: Results from two randomized placebo-controlled phase 3 trials. Allergy. 2022 Apr;77(4):1231-1244. doi: 10.1111/all.15067. Epub 2021 Oct 1.
Khan AH, Reaney M, Guillemin I, Nelson L, Qin S, Kamat S, Mannent L, Amin N, Whalley D, Hopkins C. Development of Sinonasal Outcome Test (SNOT-22) Domains in Chronic Rhinosinusitis With Nasal Polyps. Laryngoscope. 2022 May;132(5):933-941. doi: 10.1002/lary.29766. Epub 2021 Aug 26.
Hamilton JD, Harel S, Swanson BN, Brian W, Chen Z, Rice MS, Amin N, Ardeleanu M, Radin A, Shumel B, Ruddy M, Patel N, Pirozzi G, Mannent L, Graham NMH. Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases. Clin Exp Allergy. 2021 Jul;51(7):915-931. doi: 10.1111/cea.13954. Epub 2021 Jun 26.
Fujieda S, Matsune S, Takeno S, Ohta N, Asako M, Bachert C, Inoue T, Takahashi Y, Fujita H, Deniz Y, Rowe P, Ortiz B, Li Y, Mannent LP. Dupilumab efficacy in chronic rhinosinusitis with nasal polyps from SINUS-52 is unaffected by eosinophilic status. Allergy. 2022 Jan;77(1):186-196. doi: 10.1111/all.14906. Epub 2021 Jun 4.
Chong LY, Piromchai P, Sharp S, Snidvongs K, Webster KE, Philpott C, Hopkins C, Burton MJ. Biologics for chronic rhinosinusitis. Cochrane Database Syst Rev. 2021 Mar 12;3(3):CD013513. doi: 10.1002/14651858.CD013513.pub3.
Hopkins C, Wagenmann M, Bachert C, Desrosiers M, Han JK, Hellings PW, Lee SE, Msihid J, Radwan A, Rowe P, Amin N, Deniz Y, Ortiz B, Mannent LP, Rout R. Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2021 Jul;11(7):1087-1101. doi: 10.1002/alr.22780. Epub 2021 Feb 21.
Peters AT, Han JK, Hellings P, Heffler E, Gevaert P, Bachert C, Xu Y, Chuang CC, Neupane B, Msihid J, Mannent LP, Guyot P, Kamat S. Indirect Treatment Comparison of Biologics in Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2021 Jun;9(6):2461-2471.e5. doi: 10.1016/j.jaip.2021.01.031. Epub 2021 Feb 4.
Laidlaw TM, Bachert C, Amin N, Desrosiers M, Hellings PW, Mullol J, Maspero JF, Gevaert P, Zhang M, Mao X, Khan AH, Kamat S, Patel N, Graham NMH, Ruddy M, Staudinger H, Mannent LP. Dupilumab improves upper and lower airway disease control in chronic rhinosinusitis with nasal polyps and asthma. Ann Allergy Asthma Immunol. 2021 May;126(5):584-592.e1. doi: 10.1016/j.anai.2021.01.012. Epub 2021 Jan 16.
Fujieda S, Matsune S, Takeno S, Asako M, Takeuchi M, Fujita H, Takahashi Y, Amin N, Deniz Y, Rowe P, Mannent L. The Effect of Dupilumab on Intractable Chronic Rhinosinusitis with Nasal Polyps in Japan. Laryngoscope. 2021 Jun;131(6):E1770-E1777. doi: 10.1002/lary.29230. Epub 2020 Nov 23.
Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N, Lee SE, Mullol J, Greos LS, Bosso JV, Laidlaw TM, Cervin AU, Maspero JF, Hopkins C, Olze H, Canonica GW, Paggiaro P, Cho SH, Fokkens WJ, Fujieda S, Zhang M, Lu X, Fan C, Draikiwicz S, Kamat SA, Khan A, Pirozzi G, Patel N, Graham NMH, Ruddy M, Staudinger H, Weinreich D, Stahl N, Yancopoulos GD, Mannent LP. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019 Nov 2;394(10209):1638-1650. doi: 10.1016/S0140-6736(19)31881-1. Epub 2019 Sep 19. Erratum In: Lancet. 2019 Nov 2;394(10209):1618. doi: 10.1016/S0140-6736(19)32218-4.

Public notes

Contacts

Principal investigator

Name

Clinical Sciences & Operations

Address

Sanofi

Country

Phone

Contact person for public queries

Name

Address

Country

Phone

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Not available for request

What supporting documents are/will be available?

Type	Other Details	Attachment
Study protocol		https://cdn.clinicaltrials.gov/large-docs/54/NCT02898454/Prot_000.pdf
Statistical analysis plan		https://cdn.clinicaltrials.gov/large-docs/54/NCT02898454/SAP_001.pdf

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02898454

Trial Review

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