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A Controlled Clinical Study of Dupilumab in Patients With Bilateral Nasal Polyps (SINUS-24)

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 50 micrograms

About this trial

This is an interventional treatment trial for Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP) focused on measuring Nasal polyposis, Chronic rhinosinusitis, Intranasal corticosteroids, Dupilumab, Human monoclonal antibody

Eligibility Criteria

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

Inclusion criteria:

Participants with bilateral sinonasal polyposis that despite prior treatment with systemic corticosteroids (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 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 prior to Visit [V] 1) of nasal congestion/blockage/obstruction with moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity of greater than 1 at the 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.
Participants who were previously treated in dupilumab studies.
Participants 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 (mAB) within 5 half-lives or within 6 months before V1 if the half-life was unknown.
Anti-immunoglobulin E (IgE) 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.
Initiated allergen immunotherapy within 3 months prior to V1 or planned to begin therapy or changed its dose during the run-in period or the randomized treatment period.
Participants who undergone any intranasal and/or sinus surgery (including polypectomy) within 6 months prior to V1.
Participants who had a sinonasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS.
Participants with conditions/concomitant diseases making them nonevaluable 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 in 1 second (FEV1) 50% or less (of predicted normal).
Participants who received concomitant treatment prohibited in the study.
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 (HBsAg) 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 planned 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 Type

Placebo Comparator

Experimental

Arm Label

Placebo

Dupilumab 300 mg

Arm Description

Placebo (for dupilumab), 1 subcutaneous (SC) injection every 2 weeks (q2w) from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal mometasone furoate nasal spray (MFNS) at stable dose.

Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 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.

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.

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.

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

The TSS was the sum of participant-assessed nasal symptom scores for nasal congestion/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.

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

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

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

The SNOT-22 is a validated questionnaire that 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.

Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 24 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, dexamethasone, dexamethasone sodium phosphate, Hydrocortisone sodium succinate, methylprednisolone, prednisolone, prednisolone metasulfobenzoate sodium, prednisone, and triamcinolone. 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 24 was obtained using Kaplan-Meier method.

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 (cm) 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 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, prior surgery history, and regions as covariates.

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 are indicative of better nasal air flow. 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, prior surgery history, and regions as covariates.

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 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, prior surgery history, and regions as covariates.

Change 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 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, prior surgery history, and regions as covariates.

Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) Scores 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 the corresponding baseline value, treatment group, prior surgery, and regions as covariates.

Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Nasal Congestion Symptom Severity Score (Assessments Performed 4-24 Weeks After End of Treatment)

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, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Change From Baseline at Weeks 36 and 48 in Nasal Polyp Score (Assessments Performed 12 and 24 Weeks After End of Treatment)

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 mean and SE were obtained from ANCOVA model.

Change From Baseline at Week 48 in Opacification of Sinuses Measured by Lund-Mackay Score (Assessment Performed 24 Weeks After End of Treatment)

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, prior surgery history, and regions as covariates.

Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Total Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment)

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 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, prior surgery history, and regions as covariates.

Change From Baseline at Week 48 in University of Pennsylvania Smell Identification Test (Assessment Performed 24 Weeks After End of Treatment)

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 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, prior surgery history, and regions as covariates.

Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily (Assessments Performed 4-24 Weeks After End of Treatment)

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 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, prior surgery history, and regions as covariates.

Change From Baseline at Weeks 36 and 48 in 22-item Sino-nasal Outcome Test Scores (Assessments Performed 12 and 24 Weeks After End of Treatment)

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. 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, prior surgery history, and regions as covariates.

Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 48 Obtained Using Kaplan-Meier Method

Rescue treatment was defined as usage of SCS or NP surgery (actual or planned) during the study. Rescue treatment included: SCS: Betamethasone, dexamethasone, dexamethasone sodium phosphate, Hydrocortisone sodium succinate, methylprednisolone, prednisolone, prednisolone metasulfobenzoate sodium, prednisone, and triamcinolone. 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 48 was obtained using Kaplan-Meier method.

Change From Baseline at Weeks 36 and 48 in Visual Analog Scale for Rhinosinusitis (Assessments Performed 12 and 24 Weeks After End of Treatment)

The VAS for rhinosinusitis was used to evaluate the total disease severity. The participants were asked to indicate on a 10 cm 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 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, prior surgery history, and regions as covariates.

Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Rhinorrhea Daily Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment)

Change From Baseline at Week 48 in Forced Expiratory Volume in 1 Second for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment)

Change From Baseline at Week 48 in Asthma Control Questionnaire-6 Scores for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment)

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 study drug until 98 days following the last administration of study drug. Serious adverse event (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.

Functional Dupilumab Concentration in Serum

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

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.

Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period

SCS included: Betamethasone, dexamethasone, dexamethasone sodium phosphate, hydrocortisone sodium succinate, methylprednisolone, prednisolone, prednisolone metasulfobenzoate sodium, prednisone, and triamcinolone. For every participant, total dose was calculated as (prescribed total daily dose*duration of SCS use). Then, mean of the total dose of 25 participants (placebo group) and 9 participants (Dupilumab group) 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.

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

The EQ-5D was a standardized HRQoL questionnaire consisting of EQ-5D descriptive system and EQ VAS. 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).

Change From Baseline at Week 24 in Nasal Congestion 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.

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

NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting ANCOVA model with corresponding baseline, treatment group, 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.

Change From Baseline at Week 24 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 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, 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.

Full Information

NCT ID

NCT02912468

First Posted

September 21, 2016

Last Updated

July 3, 2019

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02912468

Brief Title

A Controlled Clinical Study of Dupilumab in Patients With Bilateral Nasal Polyps

Acronym

SINUS-24

Official Title

A Randomized, 24-Week Treatment, Double-blind, Placebo-controlled Efficacy and Safety Study of Dupilumab 300 mg Every Other Week, in Patients With Bilateral Nasal Polyposis on a Background Therapy With Intranasal Corticosteroids

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Completed

Study Start Date

December 5, 2016 (Actual)

Primary Completion Date

July 5, 2018 (Actual)

Study Completion Date

July 5, 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 milligram (mg) every 2 weeks (q2w) compared to placebo on a background of mometasone furoate nasal spray (MFNS) in reducing nasal congestion/obstruction (NC) severity and endoscopic nasal polyp score (NPS) in participants with bilateral nasal polyposis (NP). In addition for Japan participants, reduction in computed tomography (CT) scan opacification of the sinuses was a coprimary objective. Secondary Objectives: To evaluate the efficacy of dupilumab in improving total symptoms score (TSS). 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 Japan). To evaluate ability of dupilumab in reducing proportion of participants requiring treatment with systemic corticosteroids or NP surgery. To evaluate the effect of dupilumab on participant reported outcomes and health related quality of life outcome by sinonasal outcome test-22 (SNOT-22). To evaluate the effect of dupilumab in the subgroups of participants with prior surgery and co-morbid asthma (including non-steroid antiinflammatory drug [NSAID] exacerbated respiratory disease [ERD]). To evaluate residual effect in follow up. 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 expected to be up to 52 weeks that consisted of a 4-weeks run-in period, 24-weeks treatment period, and a 24-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)

Keywords

Nasal polyposis, Chronic rhinosinusitis, Intranasal corticosteroids, Dupilumab, Human monoclonal antibody

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Masking Description

Dupilumab and placebo were provided in matching 2 milliliter (mL) pre-filled syringes. To protect the blind, each treatment kit was prepared such that the dupilumab dose and its corresponding placebo volume were identical and indistinguishable and were labelled with a treatment kit number.

Allocation

Randomized

Enrollment

276 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Dupilumab 300 mg

Arm Type

Experimental

Arm Description

Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 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 50 micrograms

Other Intervention Name(s)

NASONEX®

Intervention Description

Pharmaceutical form: Suspension (Nasal spray) 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

Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 24 Obtained Using Kaplan-Meier Method

Description

Time Frame

Baseline up to Week 24

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 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 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 24 in Asthma Control Questionnaire-6 (ACQ-6) Scores for Participants With Asthma

Description

Time Frame

Baseline, Week 24

Title

Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Nasal Congestion Symptom Severity Score (Assessments Performed 4-24 Weeks After End of Treatment)

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 ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Time Frame

Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment)

Title

Change From Baseline at Weeks 36 and 48 in Nasal Polyp Score (Assessments Performed 12 and 24 Weeks After End of Treatment)

Description

Time Frame

Baseline, Week 36, Week 48 (post-baseline assessments performed 12 and 24 weeks after end of treatment)

Title

Change From Baseline at Week 48 in Opacification of Sinuses Measured by Lund-Mackay Score (Assessment Performed 24 Weeks After End of Treatment)

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, prior surgery history, and regions as covariates.

Time Frame

Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment)

Title

Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Total Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment)

Description

Time Frame

Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment)

Title

Change From Baseline at Week 48 in University of Pennsylvania Smell Identification Test (Assessment Performed 24 Weeks After End of Treatment)

Description

Time Frame

Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment)

Title

Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily (Assessments Performed 4-24 Weeks After End of Treatment)

Description

Time Frame

Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment)

Title

Change From Baseline at Weeks 36 and 48 in 22-item Sino-nasal Outcome Test Scores (Assessments Performed 12 and 24 Weeks After End of Treatment)

Description

Time Frame

Baseline, Week 36 and Week 48 (Post-baseline assessments performed 12 and 24 weeks after end of treatment)

Title

Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 48 Obtained Using Kaplan-Meier Method

Description

Time Frame

Baseline up to Week 48

Title

Change From Baseline at Weeks 36 and 48 in Visual Analog Scale for Rhinosinusitis (Assessments Performed 12 and 24 Weeks After End of Treatment)

Description

Time Frame

Baseline, Week 36 and Week 48 (Post-baseline assessments performed 12 and 24 weeks after end of treatment)

Title

Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Rhinorrhea Daily Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment)

Description

Time Frame

Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment)

Title

Change From Baseline at Week 48 in Forced Expiratory Volume in 1 Second for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment)

Description

Time Frame

Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment)

Title

Change From Baseline at Week 48 in Asthma Control Questionnaire-6 Scores for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment)

Description

Time Frame

Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment)

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 98 days following the last administration of study drug (up to 36 weeks)

Title

Functional Dupilumab Concentration in Serum

Time Frame

Baseline, Week 4, 8, 16, 24, 36, End of study (Week 48)

Title

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

Description

Time Frame

Baseline to End of study (Week 48)

Title

Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period

Description

Time Frame

Baseline to Week 24

Title

Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant

Description

Time Frame

Baseline to Week 24

Title

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

Description

Time Frame

Baseline, Week 24

Title

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

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 ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates.

Time Frame

Baseline, Week 24

Title

Change From Baseline at Week 24 in Nasal Congestion 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 ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, and regions as covariates.

Time Frame

Baseline, Week 24

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 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 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 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, prior surgery history, and regions as covariates.

Time Frame

Baseline, Week 24

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.

Time Frame

Baseline, Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Participants with bilateral sinonasal polyposis that despite prior treatment with systemic corticosteroids (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 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 prior to Visit [V] 1) of nasal congestion/blockage/obstruction with moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity of greater than 1 at the 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. Participants who were previously treated in dupilumab studies. Participants 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 (mAB) within 5 half-lives or within 6 months before V1 if the half-life was unknown. Anti-immunoglobulin E (IgE) 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. Initiated allergen immunotherapy within 3 months prior to V1 or planned to begin therapy or changed its dose during the run-in period or the randomized treatment period. Participants who undergone any intranasal and/or sinus surgery (including polypectomy) within 6 months prior to V1. Participants who had a sinonasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS. Participants with conditions/concomitant diseases making them nonevaluable 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 in 1 second (FEV1) 50% or less (of predicted normal). Participants who received concomitant treatment prohibited in the study. 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 (HBsAg) 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 planned 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 8400009

City

Long Beach

State/Province

California

ZIP/Postal Code

90720

Country

United States

Facility Name

Investigational Site Number 8400004

City

Orange

State/Province

California

ZIP/Postal Code

92868

Country

United States

Facility Name

Investigational Site Number 8400014

City

San Diego

State/Province

California

ZIP/Postal Code

92123

Country

United States

Facility Name

Investigational Site Number 8400002

City

Stockton

State/Province

California

ZIP/Postal Code

95207

Country

United States

Facility Name

Investigational Site Number 8400016

City

Centennial

State/Province

Colorado

ZIP/Postal Code

80112

Country

United States

Facility Name

Investigational Site Number 8400013

City

Tampa

State/Province

Florida

ZIP/Postal Code

33613

Country

United States

Facility Name

Investigational Site Number 8400022

City

West Des Moines

State/Province

Iowa

ZIP/Postal Code

50265

Country

United States

Facility Name

Investigational Site Number 8400007

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Investigational Site Number 8400005

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Investigational Site Number 8400021

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63141

Country

United States

Facility Name

Investigational Site Number 8400008

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27103

Country

United States

Facility Name

Investigational Site Number 8400019

City

Tulsa

State/Province

Oklahoma

ZIP/Postal Code

74136

Country

United States

Facility Name

Investigational Site Number 8400020

City

Medford

State/Province

Oregon

ZIP/Postal Code

97504

Country

United States

Facility Name

Investigational Site Number 8400018

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

Investigational Site Number 8400003

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232-8695

Country

United States

Facility Name

Investigational Site Number 8400001

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

Investigational Site Number 8400015

City

Norfolk

State/Province

Virginia

ZIP/Postal Code

23507

Country

United States

Facility Name

Investigational Site Number 8400010

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

Facility Name

Investigational Site Number 1000003

City

Plovdiv

ZIP/Postal Code

4002

Country

Bulgaria

Facility Name

Investigational Site Number 1000002

City

Sofia

ZIP/Postal Code

1527

Country

Bulgaria

Facility Name

Investigational Site Number 1000001

City

Sofia

ZIP/Postal Code

1606

Country

Bulgaria

Facility Name

Investigational Site Number 2030001

City

Hradec Kralove

ZIP/Postal Code

50005

Country

Czechia

Facility Name

Investigational Site Number 2030002

City

Pardubice

ZIP/Postal Code

53203

Country

Czechia

Facility Name

Investigational Site Number 2030004

City

Praha 2

ZIP/Postal Code

12808

Country

Czechia

Facility Name

Investigational Site Number 2500005

City

La Roche Sur Yon

ZIP/Postal Code

85925

Country

France

Facility Name

Investigational Site Number 2500007

City

Lille

ZIP/Postal Code

59000

Country

France

Facility Name

Investigational Site Number 2500003

City

Lyon

ZIP/Postal Code

69317

Country

France

Facility Name

Investigational Site Number 2500001

City

Montpellier

ZIP/Postal Code

34000

Country

France

Facility Name

Investigational Site Number 2500006

City

Nantes

ZIP/Postal Code

44035

Country

France

Facility Name

Investigational Site Number 2500002

City

Toulouse

ZIP/Postal Code

31059

Country

France

Facility Name

Investigational Site Number 2500004

City

Vandoeuvre-Les-Nancy

ZIP/Postal Code

54511

Country

France

Facility Name

Investigational Site Number 2760001

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Investigational Site Number 2760003

City

München

ZIP/Postal Code

81377

Country

Germany

Facility Name

Investigational Site Number 2760002

City

Münster

ZIP/Postal Code

48149

Country

Germany

Facility Name

Investigational Site Number 3480006

City

Budapest

ZIP/Postal Code

1062

Country

Hungary

Facility Name

Investigational Site Number 3480007

City

Budapest

ZIP/Postal Code

1083

Country

Hungary

Facility Name

Investigational Site Number 3480004

City

Budapest

ZIP/Postal Code

1115

Country

Hungary

Facility Name

Investigational Site Number 3480003

City

Budapest

ZIP/Postal Code

1125

Country

Hungary

Facility Name

Investigational Site Number 3480005

City

Debrecen

ZIP/Postal Code

4032

Country

Hungary

Facility Name

Investigational Site Number 3480002

City

Pécs

ZIP/Postal Code

7621

Country

Hungary

Facility Name

Investigational Site Number 3480001

City

Szeged

ZIP/Postal Code

6725

Country

Hungary

Facility Name

Investigational Site Number 3800007

City

Bologna

ZIP/Postal Code

40139

Country

Italy

Facility Name

Investigational Site Number 3800002

City

Catania

ZIP/Postal Code

95123

Country

Italy

Facility Name

Investigational Site Number 3800004

City

Milano

ZIP/Postal Code

20132

Country

Italy

Facility Name

Investigational Site Number 3800006

City

Milano

ZIP/Postal Code

20142

Country

Italy

Facility Name

Investigational Site Number 3800001

City

Pisa

ZIP/Postal Code

56124

Country

Italy

Facility Name

Investigational Site Number 3800005

City

Rozzano

ZIP/Postal Code

20089

Country

Italy

Facility Name

Investigational Site Number 3800003

City

Varese

ZIP/Postal Code

21100

Country

Italy

Facility Name

Investigational Site Number 5280001

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

Investigational Site Number 6160002

City

Katowice

ZIP/Postal Code

40-611

Country

Poland

Facility Name

Investigational Site Number 6160001

City

Lodz

ZIP/Postal Code

90-153

Country

Poland

Facility Name

Investigational Site Number 6160003

City

Warszawa

ZIP/Postal Code

04-141

Country

Poland

Facility Name

Investigational Site Number 6420007

City

Brasov

ZIP/Postal Code

500283

Country

Romania

Facility Name

Investigational Site Number 6420013

City

Brasov

ZIP/Postal Code

500283

Country

Romania

Facility Name

Investigational Site Number 6420003

City

Bucuresti

ZIP/Postal Code

011172

Country

Romania

Facility Name

Investigational Site Number 6420009

City

Cluj-Napoca

ZIP/Postal Code

400015

Country

Romania

Facility Name

Investigational Site Number 6420008

City

Craiova

ZIP/Postal Code

200642

Country

Romania

Facility Name

Investigational Site Number 6420010

City

Targu-Mures

ZIP/Postal Code

540098

Country

Romania

Facility Name

Investigational Site Number 6430004

City

Moscow

ZIP/Postal Code

119435

Country

Russian Federation

Facility Name

Investigational Site Number 6430003

City

Moscow

ZIP/Postal Code

129090

Country

Russian Federation

Facility Name

Investigational Site Number 6430001

City

Saint-Petersburg

ZIP/Postal Code

195030

Country

Russian Federation

Facility Name

Investigational Site Number 6430007

City

Saint-Petersburg

ZIP/Postal Code

197022

Country

Russian Federation

Facility Name

Investigational Site Number 6430002

City

St-Petersburg

ZIP/Postal Code

190013

Country

Russian Federation

Facility Name

Investigational Site Number 6430006

City

Yaroslavl

ZIP/Postal Code

150003

Country

Russian Federation

Facility Name

Investigational Site Number 8040002

City

Ivano-Frankivsk

ZIP/Postal Code

76000

Country

Ukraine

Facility Name

Investigational Site Number 8040004

City

Kharkiv

ZIP/Postal Code

61166

Country

Ukraine

Facility Name

Investigational Site Number 8040005

City

Kyiv

ZIP/Postal Code

01133

Country

Ukraine

Facility Name

Investigational Site Number 8040006

City

Kyiv

ZIP/Postal Code

03680

Country

Ukraine

Facility Name

Investigational Site Number 8040001

City

Poltava

ZIP/Postal Code

36011

Country

Ukraine

Facility Name

Investigational Site Number 8040008

City

Ternopil

ZIP/Postal Code

46000

Country

Ukraine

Facility Name

Investigational Site Number 8260001

City

Bradford

ZIP/Postal Code

BD9 6RJ

Country

United Kingdom

Facility Name

Investigational Site Number 8260002

City

Dundee

ZIP/Postal Code

DD1 9SY

Country

United Kingdom

Facility Name

Investigational Site Number 8260007

City

Great Yarmouth

ZIP/Postal Code

NR31 6LA

Country

United Kingdom

Facility Name

Investigational Site Number 8260006

City

London

ZIP/Postal Code

SE1 7EH

Country

United Kingdom

Facility Name

Investigational Site Number 8260004

City

Stockport

ZIP/Postal Code

SK2 7JE

Country

United Kingdom

Facility Name

Investigational Site Number 8260005

City

Wigan

ZIP/Postal Code

WN1 2NN

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Not yet available

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34970860

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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.

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31543428

Citation

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.

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A Controlled Clinical Study of Dupilumab in Patients With Bilateral Nasal Polyps

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A Controlled Clinical Study of Dupilumab in Patients With Bilateral Nasal Polyps (SINUS-24)

Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

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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

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