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Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps (SINUS-52)

Primary Purpose

Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Dupilumab SAR231893 (REGN668)

Placebo

Mometasone furoate nasal spray

About this trial

This is an interventional treatment trial for Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Dupilumab 300 mg q2w

Dupilumab 300 mg q2w then q4w

Placebo

Arm Description

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.

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 (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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

Change From Baseline at Week 52 in Rhinorrhea Daily Symptom Score

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.

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.

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.

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

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.

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

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.

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

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

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.

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.

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

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

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

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.

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.

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.

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.

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.

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.

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

Functional Dupilumab Concentration in Serum

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.

Full Information

NCT ID

NCT02898454

First Posted

September 8, 2016

Last Updated

October 3, 2019

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02898454

Brief Title

Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps

Acronym

SINUS-52

Official 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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

November 28, 2016 (Actual)

Primary Completion Date

August 27, 2018 (Actual)

Study Completion Date

November 16, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

The total study duration per participant was up to 68 weeks that consisted of a 4-weeks run-in period, 52-weeks treatment period, and a 12-weeks post treatment period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

448 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dupilumab 300 mg q2w

Arm Type

Experimental

Arm Description

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.

Arm Title

Dupilumab 300 mg q2w then q4w

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Dupilumab SAR231893 (REGN668)

Intervention Description

Pharmaceutical form: Solution Route of administration: Subcutaneous

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Pharmaceutical form: Solution Route of administration: Subcutaneous

Intervention Type

Drug

Intervention Name(s)

Mometasone furoate nasal spray

Other Intervention Name(s)

NASONEX®

Intervention Description

Pharmaceutical form: Suspension Route of administration: Intranasal

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline, Week 24

Title

Change From Baseline at Week 24 in Nasal Polyp Score

Description

Time Frame

Baseline, Week 24

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 24

Title

Change From Baseline at Week 52 in Nasal Polyp Score

Description

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

Baseline up to 52 weeks

Title

Change From Baseline at Week 52 in Total Symptom Score

Description

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.

Time Frame

Baseline, Week 52

Title

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

Description

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.

Time Frame

Baseline, Week 52

Title

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

Description

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.

Time Frame

Baseline, Week 52

Title

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

Description

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.

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

Baseline, Week 24

Title

Change From Baseline at Week 24 in Rhinorrhea Daily Symptom Score

Description

Time Frame

Baseline, Week 24

Title

Change From Baseline at Week 52 in Rhinorrhea Daily Symptom Score

Description

Time Frame

Baseline, Week 52

Title

Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period

Description

Time Frame

Baseline to Week 52

Title

Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant

Description

Time Frame

Baseline to Week 52

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

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.

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 52

Title

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

Description

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.

Time Frame

Baseline, Week 24

Title

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

Description

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.

Time Frame

Baseline, Week 52

Title

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

Description

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.

Time Frame

Baseline, Week 24

Title

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

Description

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.

Time Frame

Baseline, Week 52

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 52

Title

Functional Dupilumab Concentration in Serum

Time Frame

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

Title

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

Description

Time Frame

Baseline to Week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Sciences & Operations

Organizational Affiliation

Sanofi

Official's Role

Study Director

Facility Information:

Facility Name

Investigational Site Number 8400019

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35209

Country

United States

Facility Name

Investigational Site Number 8400011

City

Fresno

State/Province

California

ZIP/Postal Code

93720

Country

United States

Facility Name

Investigational Site Number 8400008

City

Huntington Beach

State/Province

California

ZIP/Postal Code

92647

Country

United States

Facility Name

Investigational Site Number 8400004

City

Rolling Hills Estates

State/Province

California

ZIP/Postal Code

90274

Country

United States

Facility Name

Investigational Site Number 8400012

City

Walnut Creek

State/Province

California

ZIP/Postal Code

94598

Country

United States

Facility Name

Investigational Site Number 8400017

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80909

Country

United States

Facility Name

Investigational Site Number 8400006

City

Denver

State/Province

Colorado

ZIP/Postal Code

80230

Country

United States

Facility Name

Investigational Site Number 8400022

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06519

Country

United States

Facility Name

Investigational Site Number 8400002

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40207

Country

United States

Facility Name

Investigational Site Number 8400021

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Investigational Site Number 8400014

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64114

Country

United States

Facility Name

Investigational Site Number 8400024

City

Bronx

State/Province

New York

ZIP/Postal Code

10461

Country

United States

Facility Name

Investigational Site Number 8400016

City

North Charleston

State/Province

North Carolina

ZIP/Postal Code

29420

Country

United States

Facility Name

Investigational Site Number 8400013

City

Bethlehem

State/Province

Pennsylvania

ZIP/Postal Code

18017

Country

United States

Facility Name

Investigational Site Number 8400005

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Investigational Site Number 8400003

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Facility Name

Investigational Site Number 8400009

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84132

Country

United States

Facility Name

Investigational Site Number 8400010

City

Bellevue

State/Province

Washington

ZIP/Postal Code

98225

Country

United States

Facility Name

Investigational Site Number 8400007

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53219

Country

United States

Facility Name

Investigational Site Number 0320006

City

Buenos Aires

ZIP/Postal Code

B1602DQD

Country

Argentina

Facility Name

Investigational Site Number 0320004

City

Buenos Aires

ZIP/Postal Code

C1121ABE

Country

Argentina

Facility Name

Investigational Site Number 0320005

City

Caba

ZIP/Postal Code

C1414AIF

Country

Argentina

Facility Name

Investigational Site Number 0320001

City

Caba

ZIP/Postal Code

C1425BEN

Country

Argentina

Facility Name

Investigational Site Number 0320007

City

Caba

ZIP/Postal Code

C1426ABP

Country

Argentina

Facility Name

Investigational Site Number 0320003

City

Mendoza

ZIP/Postal Code

5500

Country

Argentina

Facility Name

Investigational Site Number 0320008

City

Rosario

ZIP/Postal Code

S2000DBS

Country

Argentina

Facility Name

Investigational Site Number 0320002

City

San Miguel De Tucumán

ZIP/Postal Code

T4000IAR

Country

Argentina

Facility Name

Investigational Site Number 0360002

City

Clayton

ZIP/Postal Code

3168

Country

Australia

Facility Name

Investigational Site Number 0360004

City

Herston

ZIP/Postal Code

4029

Country

Australia

Facility Name

Investigational Site Number 0360005

City

Murdoch

ZIP/Postal Code

6150

Country

Australia

Facility Name

Investigational Site Number 0360001

City

Parkville

ZIP/Postal Code

3050

Country

Australia

Facility Name

Investigational Site Number 0360003

City

Prahran

ZIP/Postal Code

3004

Country

Australia

Facility Name

Investigational Site Number 0560003

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Investigational Site Number 0560001

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

Investigational Site Number 0560002

City

Leuven

ZIP/Postal Code

3500

Country

Belgium

Facility Name

Investigational Site Number 1240007

City

Kingston

ZIP/Postal Code

K7L 2V7

Country

Canada

Facility Name

Investigational Site Number 1240002

City

Montreal

ZIP/Postal Code

H2W 1T8

Country

Canada

Facility Name

Investigational Site Number 1240006

City

Montreal

ZIP/Postal Code

H4A 3J1

Country

Canada

Facility Name

Investigational Site Number 1240005

City

Ottawa

ZIP/Postal Code

K1G 6C6

Country

Canada

Facility Name

Investigational Site Number 1240003

City

Quebec

ZIP/Postal Code

G1V 4G5

Country

Canada

Facility Name

Investigational Site Number 1240004

City

Quebec

ZIP/Postal Code

G1V 4W2

Country

Canada

Facility Name

Investigational Site Number 1240008

City

Trois-Rivieres

ZIP/Postal Code

G8T 7A1

Country

Canada

Facility Name

Investigational Site Number 1240001

City

Vancouver

ZIP/Postal Code

V5Z 1M9

Country

Canada

Facility Name

Investigational Site Number 1520009

City

Quillota

ZIP/Postal Code

2260877

Country

Chile

Facility Name

Investigational Site Number 1520010

City

San Fernando

Country

Chile

Facility Name

Investigational Site Number 1520005

City

Santiago

ZIP/Postal Code

7500010

Country

Chile

Facility Name

Investigational Site Number 1520011

City

Santiago

ZIP/Postal Code

7500571

Country

Chile

Facility Name

Investigational Site Number 1520008

City

Santiago

ZIP/Postal Code

7500692

Country

Chile

Facility Name

Investigational Site Number 1520006

City

Santiago

ZIP/Postal Code

7980378

Country

Chile

Facility Name

Investigational Site Number 1520001

City

Santiago

ZIP/Postal Code

8207257

Country

Chile

Facility Name

Investigational Site Number 1520014

City

Santiago

ZIP/Postal Code

8910131

Country

Chile

Facility Name

Investigational Site Number 1520003

City

Talca

Country

Chile

Facility Name

Investigational Site Number 1520007

City

Viña Del Mar

Country

Chile

Facility Name

Investigational Site Number 3760001

City

Hadera

ZIP/Postal Code

38100

Country

Israel

Facility Name

Investigational Site Number 3760003

City

Nahariya

ZIP/Postal Code

22100

Country

Israel

Facility Name

Investigational Site Number 3760002

City

Petah-Tikva

ZIP/Postal Code

49100

Country

Israel

Facility Name

Investigational Site Number 3760005

City

Rehovot

ZIP/Postal Code

76100

Country

Israel

Facility Name

Investigational Site Number 3760004

City

Tel Hashomer

ZIP/Postal Code

52621

Country

Israel

Facility Name

Investigational Site Number 3920004

City

Bunkyo-Ku

Country

Japan

Facility Name

Investigational Site Number 3920009

City

Bunkyo-Ku

Country

Japan

Facility Name

Investigational Site Number 3920026

City

Bunkyo-Ku

Country

Japan

Facility Name

Investigational Site Number 3920006

City

Chiyoda-Ku

Country

Japan

Facility Name

Investigational Site Number 3920024

City

Fukuoka-Shi

Country

Japan

Facility Name

Investigational Site Number 3920010

City

Hirakata-Shi

Country

Japan

Facility Name

Investigational Site Number 3920011

City

Hiroshima-Shi

Country

Japan

Facility Name

Investigational Site Number 3920007

City

Iida-Shi

Country

Japan

Facility Name

Investigational Site Number 3920015

City

Inzai-Shi

Country

Japan

Facility Name

Investigational Site Number 3920012

City

Itabashi-Ku

Country

Japan

Facility Name

Investigational Site Number 3920014

City

Izumisano-Shi

Country

Japan

Facility Name

Investigational Site Number 3920016

City

Kawasaki-Shi

Country

Japan

Facility Name

Investigational Site Number 3920020

City

Kitakyushu-Shi

Country

Japan

Facility Name

Investigational Site Number 3920027

City

Kitakyushu-Shi

Country

Japan

Facility Name

Investigational Site Number 3920002

City

Kumamoto-Shi

Country

Japan

Facility Name

Investigational Site Number 3920021

City

Kumamoto-Shi

Country

Japan

Facility Name

Investigational Site Number 3920003

City

Kyoto-Shi

Country

Japan

Facility Name

Investigational Site Number 3920023

City

Meguro-Ku

Country

Japan

Facility Name

Investigational Site Number 3920013

City

Moriguchi-Shi

Country

Japan

Facility Name

Investigational Site Number 3920025

City

Okayama-Shi

Country

Japan

Facility Name

Investigational Site Number 3920018

City

Osaka-Shi

Country

Japan

Facility Name

Investigational Site Number 3920017

City

Ota-Ku

Country

Japan

Facility Name

Investigational Site Number 3920005

City

Sendai-Shi

Country

Japan

Facility Name

Investigational Site Number 3920022

City

Sendai-Shi

Country

Japan

Facility Name

Investigational Site Number 3920001

City

Shimonoseki-Shi

Country

Japan

Facility Name

Investigational Site Number 3920029

City

Shinagawa-Ku

Country

Japan

Facility Name

Investigational Site Number 3920030

City

Shinjyuku-Ku

Country

Japan

Facility Name

Investigational Site Number 3920028

City

Takatsuki-Shi

Country

Japan

Facility Name

Investigational Site Number 3920019

City

Yoshida-Gun

Country

Japan

Facility Name

Investigational Site Number 4840001

City

Chihuahua

ZIP/Postal Code

31000

Country

Mexico

Facility Name

Investigational Site Number 4840005

City

Chihuahua

ZIP/Postal Code

31200

Country

Mexico

Facility Name

Investigational Site Number 4840004

City

Durango

ZIP/Postal Code

34080

Country

Mexico

Facility Name

Investigational Site Number 4840002

City

Guadalajara

ZIP/Postal Code

44100

Country

Mexico

Facility Name

Investigational Site Number 4840003

City

Monterrey

ZIP/Postal Code

64460

Country

Mexico

Facility Name

Investigational Site Number 6200004

City

Aveiro

ZIP/Postal Code

3810-501

Country

Portugal

Facility Name

Investigational Site Number 6200006

City

Guimarães

ZIP/Postal Code

4810-061

Country

Portugal

Facility Name

Investigational Site Number 6200002

City

Lisboa

ZIP/Postal Code

1349-019

Country

Portugal

Facility Name

Investigational Site Number 6200007

City

Matosinhos

ZIP/Postal Code

4460-188

Country

Portugal

Facility Name

Investigational Site Number 6200001

City

Porto

ZIP/Postal Code

4099-001

Country

Portugal

Facility Name

Investigational Site Number 6200005

City

Viana Do Castelo

ZIP/Postal Code

4901-858

Country

Portugal

Facility Name

Investigational Site Number 6430006

City

Moscow

ZIP/Postal Code

123182

Country

Russian Federation

Facility Name

Investigational Site Number 6430003

City

Odintsovo

ZIP/Postal Code

143005

Country

Russian Federation

Facility Name

Investigational Site Number 6430002

City

Saint-Petersburg

ZIP/Postal Code

197022

Country

Russian Federation

Facility Name

Investigational Site Number 6430005

City

Stavropol

ZIP/Postal Code

355030

Country

Russian Federation

Facility Name

Investigational Site Number 6430001

City

Yaroslavl

ZIP/Postal Code

150062

Country

Russian Federation

Facility Name

Investigational Site Number 7240001

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Investigational Site Number 7240006

City

Barcelona

ZIP/Postal Code

08041

Country

Spain

Facility Name

Investigational Site Number 7240003

City

Jerez De La Frontera

ZIP/Postal Code

11407

Country

Spain

Facility Name

Investigational Site Number 7240002

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Investigational Site Number 7240007

City

Sevilla

ZIP/Postal Code

41071

Country

Spain

Facility Name

Investigational Site Number 7240009

City

Valencia

ZIP/Postal Code

46026

Country

Spain

Facility Name

Investigational Site Number 7520002

City

Lund

ZIP/Postal Code

221 85

Country

Sweden

Facility Name

Investigational Site Number 7520001

City

Stockholm

ZIP/Postal Code

171 76

Country

Sweden

Facility Name

Investigational Site Number 7920004

City

Ankara

ZIP/Postal Code

06100

Country

Turkey

Facility Name

Investigational Site Number 7920005

City

Ankara

ZIP/Postal Code

06500

Country

Turkey

Facility Name

Investigational Site Number 7920008

City

Ankara

ZIP/Postal Code

06520

Country

Turkey

Facility Name

Investigational Site Number 7920013

City

Bursa

ZIP/Postal Code

16059

Country

Turkey

Facility Name

Investigational Site Number 7920010

City

Istanbul

ZIP/Postal Code

34010

Country

Turkey

Facility Name

Investigational Site Number 7920009

City

Istanbul

ZIP/Postal Code

34360

Country

Turkey

Facility Name

Investigational Site Number 7920003

City

Istanbul

ZIP/Postal Code

34373

Country

Turkey

Facility Name

Investigational Site Number 7920001

City

Istanbul

ZIP/Postal Code

34390

Country

Turkey

Facility Name

Investigational Site Number 7920002

City

Istanbul

ZIP/Postal Code

34764

Country

Turkey

Facility Name

Investigational Site Number 7920006

City

Izmir

ZIP/Postal Code

35100

Country

Turkey

Facility Name

Investigational Site Number 7920007

City

Izmir

ZIP/Postal Code

35340

Country

Turkey

Facility Name

Investigational Site Number 7920011

City

Rize

ZIP/Postal Code

53100

Country

Turkey

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Not available for request

Citations:

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35775319

Citation

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PubMed Identifier

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PubMed Identifier

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Learn more about this trial

Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps

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Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps (SINUS-52)

Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial