Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps
- Conditions
- Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)
- Interventions
- Registration Number
- NCT02898454
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 448
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dupilumab 300 mg q2w Dupilumab SAR231893 (REGN668) 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 q2w then q4w Dupilumab SAR231893 (REGN668) 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. Dupilumab 300 mg q2w then q4w Placebo 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. Dupilumab 300 mg q2w then q4w Mometasone furoate nasal spray 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 Placebo Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose. Dupilumab 300 mg q2w Mometasone furoate nasal spray 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. Placebo Mometasone furoate nasal spray 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.
- Primary Outcome Measures
Name Time Method Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score Baseline, Week 24 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 Baseline, Week 24 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
Name Time Method Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay (LMK) Score Baseline, Week 24 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) Baseline, Week 24 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 Baseline, Week 24 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 Baseline, Week 24 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 Baseline, Week 24 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 Baseline, Week 52 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 Baseline, Week 52 NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview.
Change From Baseline at Week 52 in 22-item Sino-nasal Outcome Test Scores Baseline, Week 52 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 Baseline up to 52 weeks 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 Baseline, Week 52 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 Baseline, Week 52 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 Baseline, Week 52 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 Baseline, Week 52 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 52 in Forced Expiratory Volume in 1 Second for Participants With Asthma Baseline, Week 52 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.
Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis Baseline, Week 24 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 Baseline, Week 52 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.
Change From Baseline at Week 24 in Nasal Peak Inspiratory Flow (NPIF) Baseline, Week 24 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 Baseline, Week 24 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 Baseline, Week 52 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.
Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period Baseline to Week 52 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 Baseline to Week 52 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 Baseline, Week 24 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 24 in Asthma Control Questionnaire-6 (ACQ-6) for Participants With Asthma Baseline, Week 24 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 Baseline, Week 52 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.
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma Baseline, Week 24 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 Baseline, Week 52 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/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery Baseline, Week 24 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 Prior Nasal Polyp Surgery Baseline, Week 52 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 Baseline, Week 24 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 Baseline, Week 52 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 Baseline, Week 24 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 Prior Nasal Polyp Surgery Baseline, Week 52 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 Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma Baseline, Week 24 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 Baseline, Week 52 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 Baseline, Week 24 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 Baseline, Week 52 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 Baseline up to 84 days after last dose of study drug (up to 64 weeks) 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 Baseline, Week 24 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 Baseline, Week 52 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).
Functional Dupilumab Concentration in Serum Baseline, Week 2, Week 4, Week 16, Week 24, Week 40, End of treatment (Week 52), End of study (Week 64) Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies Response (ADA) Baseline to Week 52 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.
Trial Locations
- Locations (123)
Investigational Site Number 8400011
🇺🇸Fresno, California, United States
Investigational Site Number 0320005
🇦🇷Caba, Argentina
Investigational Site Number 0320004
🇦🇷Buenos Aires, Argentina
Investigational Site Number 1240002
🇨🇦Montreal, Canada
Investigational Site Number 0320001
🇦🇷Caba, Argentina
Investigational Site Number 1240004
🇨🇦Quebec, Canada
Investigational Site Number 3760005
🇮🇱Rehovot, Israel
Investigational Site Number 3760003
🇮🇱Nahariya, Israel
Investigational Site Number 3920014
🇯🇵Izumisano-Shi, Japan
Investigational Site Number 6200007
🇵🇹Matosinhos, Portugal
Investigational Site Number 6430006
🇷🇺Moscow, Russian Federation
Investigational Site Number 8400021
🇺🇸Boston, Massachusetts, United States
Investigational Site Number 8400003
🇺🇸Pittsburgh, Pennsylvania, United States
Investigational Site Number 8400009
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 1240001
🇨🇦Vancouver, Canada
Investigational Site Number 3920021
🇯🇵Kumamoto-Shi, Japan
Investigational Site Number 8400019
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 8400008
🇺🇸Huntington Beach, California, United States
Investigational Site Number 8400012
🇺🇸Walnut Creek, California, United States
Investigational Site Number 8400004
🇺🇸Rolling Hills Estates, California, United States
Investigational Site Number 8400017
🇺🇸Colorado Springs, Colorado, United States
Investigational Site Number 8400006
🇺🇸Denver, Colorado, United States
Investigational Site Number 8400022
🇺🇸New Haven, Connecticut, United States
Investigational Site Number 8400002
🇺🇸Louisville, Kentucky, United States
Investigational Site Number 8400014
🇺🇸Kansas City, Missouri, United States
Investigational Site Number 8400016
🇺🇸North Charleston, North Carolina, United States
Investigational Site Number 8400024
🇺🇸Bronx, New York, United States
Investigational Site Number 8400013
🇺🇸Bethlehem, Pennsylvania, United States
Investigational Site Number 8400005
🇺🇸Philadelphia, Pennsylvania, United States
Investigational Site Number 8400007
🇺🇸Milwaukee, Wisconsin, United States
Investigational Site Number 0320006
🇦🇷Buenos Aires, Argentina
Investigational Site Number 8400010
🇺🇸Bellevue, Washington, United States
Investigational Site Number 0320007
🇦🇷Caba, Argentina
Investigational Site Number 0320003
🇦🇷Mendoza, Argentina
Investigational Site Number 0320008
🇦🇷Rosario, Argentina
Investigational Site Number 0320002
🇦🇷San Miguel De Tucumán, Argentina
Investigational Site Number 0360002
🇦🇺Clayton, Australia
Investigational Site Number 0360005
🇦🇺Murdoch, Australia
Investigational Site Number 0360001
🇦🇺Parkville, Australia
Investigational Site Number 0360004
🇦🇺Herston, Australia
Investigational Site Number 0360003
🇦🇺Prahran, Australia
Investigational Site Number 1240003
🇨🇦Quebec, Canada
Investigational Site Number 1240008
🇨🇦Trois-Rivieres, Canada
Investigational Site Number 1240006
🇨🇦Montreal, Canada
Investigational Site Number 0560003
🇧🇪Bruxelles, Belgium
Investigational Site Number 0560002
🇧🇪Leuven, Belgium
Investigational Site Number 1240007
🇨🇦Kingston, Canada
Investigational Site Number 0560001
🇧🇪Gent, Belgium
Investigational Site Number 1240005
🇨🇦Ottawa, Canada
Investigational Site Number 1520010
🇨🇱San Fernando, Chile
Investigational Site Number 1520009
🇨🇱Quillota, Chile
Investigational Site Number 1520005
🇨🇱Santiago, Chile
Investigational Site Number 1520001
🇨🇱Santiago, Chile
Investigational Site Number 1520011
🇨🇱Santiago, Chile
Investigational Site Number 1520006
🇨🇱Santiago, Chile
Investigational Site Number 1520014
🇨🇱Santiago, Chile
Investigational Site Number 3760001
🇮🇱Hadera, Israel
Investigational Site Number 3760002
🇮🇱Petah-Tikva, Israel
Investigational Site Number 3920004
🇯🇵Bunkyo-Ku, Japan
Investigational Site Number 3920009
🇯🇵Bunkyo-Ku, Japan
Investigational Site Number 3760004
🇮🇱Tel Hashomer, Israel
Investigational Site Number 3920010
🇯🇵Hirakata-Shi, Japan
Investigational Site Number 3920024
🇯🇵Fukuoka-Shi, Japan
Investigational Site Number 3920026
🇯🇵Bunkyo-Ku, Japan
Investigational Site Number 3920006
🇯🇵Chiyoda-Ku, Japan
Investigational Site Number 3920012
🇯🇵Itabashi-Ku, Japan
Investigational Site Number 3920007
🇯🇵Iida-Shi, Japan
Investigational Site Number 3920011
🇯🇵Hiroshima-Shi, Japan
Investigational Site Number 3920015
🇯🇵Inzai-Shi, Japan
Investigational Site Number 3920020
🇯🇵Kitakyushu-Shi, Japan
Investigational Site Number 3920002
🇯🇵Kumamoto-Shi, Japan
Investigational Site Number 3920016
🇯🇵Kawasaki-Shi, Japan
Investigational Site Number 3920027
🇯🇵Kitakyushu-Shi, Japan
Investigational Site Number 3920023
🇯🇵Meguro-Ku, Japan
Investigational Site Number 3920003
🇯🇵Kyoto-Shi, Japan
Investigational Site Number 3920025
🇯🇵Okayama-Shi, Japan
Investigational Site Number 3920013
🇯🇵Moriguchi-Shi, Japan
Investigational Site Number 3920018
🇯🇵Osaka-Shi, Japan
Investigational Site Number 3920017
🇯🇵Ota-Ku, Japan
Investigational Site Number 3920022
🇯🇵Sendai-Shi, Japan
Investigational Site Number 3920005
🇯🇵Sendai-Shi, Japan
Investigational Site Number 3920001
🇯🇵Shimonoseki-Shi, Japan
Investigational Site Number 3920028
🇯🇵Takatsuki-Shi, Japan
Investigational Site Number 3920030
🇯🇵Shinjyuku-Ku, Japan
Investigational Site Number 3920019
🇯🇵Yoshida-Gun, Japan
Investigational Site Number 3920029
🇯🇵Shinagawa-Ku, Japan
Investigational Site Number 4840004
🇲🇽Durango, Mexico
Investigational Site Number 4840003
🇲🇽Monterrey, Mexico
Investigational Site Number 4840001
🇲🇽Chihuahua, Mexico
Investigational Site Number 4840005
🇲🇽Chihuahua, Mexico
Investigational Site Number 6200004
🇵🇹Aveiro, Portugal
Investigational Site Number 6200006
🇵🇹Guimarães, Portugal
Investigational Site Number 6200002
🇵🇹Lisboa, Portugal
Investigational Site Number 6430003
🇷🇺Odintsovo, Russian Federation
Investigational Site Number 6200001
🇵🇹Porto, Portugal
Investigational Site Number 6430002
🇷🇺Saint-Petersburg, Russian Federation
Investigational Site Number 6430001
🇷🇺Yaroslavl, Russian Federation
Investigational Site Number 7240006
🇪🇸Barcelona, Spain
Investigational Site Number 6430005
🇷🇺Stavropol, Russian Federation
Investigational Site Number 7240001
🇪🇸Barcelona, Spain
Investigational Site Number 7240002
🇪🇸Madrid, Spain
Investigational Site Number 7240003
🇪🇸Jerez De La Frontera, Spain
Investigational Site Number 7240007
🇪🇸Sevilla, Spain
Investigational Site Number 7240009
🇪🇸Valencia, Spain
Investigational Site Number 7520002
🇸🇪Lund, Sweden
Investigational Site Number 7520001
🇸🇪Stockholm, Sweden
Investigational Site Number 7920001
🇹🇷Istanbul, Turkey
Investigational Site Number 7920008
🇹🇷Ankara, Turkey
Investigational Site Number 7920013
🇹🇷Bursa, Turkey
Investigational Site Number 7920005
🇹🇷Ankara, Turkey
Investigational Site Number 7920010
🇹🇷Istanbul, Turkey
Investigational Site Number 7920004
🇹🇷Ankara, Turkey
Investigational Site Number 7920009
🇹🇷Istanbul, Turkey
Investigational Site Number 7920003
🇹🇷Istanbul, Turkey
Investigational Site Number 7920002
🇹🇷Istanbul, Turkey
Investigational Site Number 7920007
🇹🇷Izmir, Turkey
Investigational Site Number 7920006
🇹🇷Izmir, Turkey
Investigational Site Number 7920011
🇹🇷Rize, Turkey
Investigational Site Number 4840002
🇲🇽Guadalajara, Mexico
Investigational Site Number 6200005
🇵🇹Viana Do Castelo, Portugal
Investigational Site Number 1520003
🇨🇱Talca, Chile
Investigational Site Number 1520008
🇨🇱Santiago, Chile
Investigational Site Number 1520007
🇨🇱Viña Del Mar, Chile
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