Trial Outcomes & Findings for Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps (NCT NCT02898454)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

448 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2019-10-23

Participant Flow

Study participants were involved in the study from 28 November 2016 to 16 November 2018 at 117 centers in 14 countries. A total of 806 participants were screened, of which 448 participants were enrolled and randomized to receive dupilumab 300 mg or placebo. A total of 358 participants had screen failures due to failure to meet inclusion criteria.

Randomization was stratified according to asthma and/or non-steroidal anti-inflammatory drug exacerbated respiratory disease (NSAID-ERD) history (yes/no), prior nasal polyps (NP) surgery (yes or not), and country.

Participant milestones

Participant milestones
Measure	Placebo Placebo (for dupilumab), 1 subcutaneous (SC) injection every 2 weeks (q2w) from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal mometasone furoate nasal spray (MFNS) at stable dose.	Dupilumab 300 mg q2w Then q4w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 and then 300 mg every 4 weeks (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 Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Overall Study STARTED	153	145	150
Overall Study Intent-to-Treat (ITT) Population	153	145	150
Overall Study Treated	152	145	150
Overall Study Safety Population	150	148	149
Overall Study COMPLETED	136	140	144
Overall Study NOT COMPLETED	17	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo (for dupilumab), 1 subcutaneous (SC) injection every 2 weeks (q2w) from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal mometasone furoate nasal spray (MFNS) at stable dose.	Dupilumab 300 mg q2w Then q4w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 and then 300 mg every 4 weeks (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 Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Overall Study Adverse Event	4	1	2
Overall Study Protocol Violation	1	0	1
Overall Study Lack of Efficacy	4	1	0
Overall Study Withdrawal by Subject	6	3	3
Overall Study Lost to Follow-up	1	0	0
Overall Study Did Not Met Eligibility Criteria	1	0	0

Baseline Characteristics

"Number analyzed" = Number of participants evaluable for the specified baseline measure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=153 Participants 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 Then q4w n=145 Participants 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 300mg q2w n=150 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.	Total n=448 Participants Total of all reporting groups
Age, Continuous	51.67 years STANDARD_DEVIATION 12.66 • n=153 Participants	52.28 years STANDARD_DEVIATION 12.87 • n=145 Participants	51.91 years STANDARD_DEVIATION 11.88 • n=150 Participants	51.95 years STANDARD_DEVIATION 12.45 • n=448 Participants
Sex: Female, Male Female	58 Participants n=153 Participants	58 Participants n=145 Participants	53 Participants n=150 Participants	169 Participants n=448 Participants
Sex: Female, Male Male	95 Participants n=153 Participants	87 Participants n=145 Participants	97 Participants n=150 Participants	279 Participants n=448 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	40 Participants n=153 Participants	42 Participants n=145 Participants	50 Participants n=150 Participants	132 Participants n=448 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	113 Participants n=153 Participants	102 Participants n=145 Participants	100 Participants n=150 Participants	315 Participants n=448 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=153 Participants	1 Participants n=145 Participants	0 Participants n=150 Participants	1 Participants n=448 Participants
Race/Ethnicity, Customized Caucasian/White	128 Participants n=153 Participants	120 Participants n=145 Participants	124 Participants n=150 Participants	372 Participants n=448 Participants
Race/Ethnicity, Customized Black/of African descent	3 Participants n=153 Participants	2 Participants n=145 Participants	2 Participants n=150 Participants	7 Participants n=448 Participants
Race/Ethnicity, Customized Asian/Oriental	18 Participants n=153 Participants	19 Participants n=145 Participants	17 Participants n=150 Participants	54 Participants n=448 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=153 Participants	2 Participants n=145 Participants	7 Participants n=150 Participants	12 Participants n=448 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=153 Participants	1 Participants n=145 Participants	0 Participants n=150 Participants	1 Participants n=448 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=153 Participants	1 Participants n=145 Participants	0 Participants n=150 Participants	2 Participants n=448 Participants
Nasal Congestion/Obstruction (NC) Symptom Severity Score	2.38 score on a scale STANDARD_DEVIATION 0.54 • n=153 Participants	2.44 score on a scale STANDARD_DEVIATION 0.59 • n=145 Participants	2.48 score on a scale STANDARD_DEVIATION 0.62 • n=150 Participants	2.43 score on a scale STANDARD_DEVIATION 0.59 • n=448 Participants
Nasal Polyp Score (NPS)	5.96 score on a scale STANDARD_DEVIATION 1.21 • n=152 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	6.29 score on a scale STANDARD_DEVIATION 1.20 • n=145 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	6.07 score on a scale STANDARD_DEVIATION 1.22 • n=149 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	6.10 score on a scale STANDARD_DEVIATION 1.21 • n=446 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The analysis was performed on intent-to-treat (ITT) population which included all randomized participants who were analyzed according to the treatment group allocated by randomization. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants 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 (24 Weeks Pooled Arm) n=295 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score	-0.38 score on a scale Standard Error 0.07	-1.25 score on a scale Standard Error 0.06	—

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=152 Participants 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 (24 Weeks Pooled Arm) n=294 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Polyp Score	0.10 score on a scale Standard Error 0.14	-1.71 score on a scale Standard Error 0.11	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=150 Participants 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 (24 Weeks Pooled Arm) n=289 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay (LMK) Score	-0.09 score on a scale Standard Error 0.31	-5.21 score on a scale Standard Error 0.24	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on ITT population. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants 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 (24 Weeks Pooled Arm) n=295 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Total Symptom Score (TSS)	-1.00 score on a scale Standard Error 0.20	-3.45 score on a scale Standard Error 0.15	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=150 Participants 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 (24 Weeks Pooled Arm) n=287 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in the University of Pennsylvania Smell Identification Test (UPSIT) Score	-0.81 score on a scale Standard Error 0.71	9.71 score on a scale Standard Error 0.56	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on ITT population. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants 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 (24 Weeks Pooled Arm) n=295 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily	-0.23 score on a scale Standard Error 0.08	-1.21 score on a scale Standard Error 0.06	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=152 Participants 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 (24 Weeks Pooled Arm) n=292 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in 22-item Sino-nasal Outcome Test (SNOT-22) Scores	-10.40 score on a scale Standard Error 1.61	-27.77 score on a scale Standard Error 1.26	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population. Here, "overall number of participants analyzed"= participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=152 Participants 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 (24 Weeks Pooled Arm) n=145 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=149 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Nasal Polyp Score	0.16 score on a scale Standard Error 0.15	-2.05 score on a scale Standard Error 0.15	-2.24 score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants 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 (24 Weeks Pooled Arm) n=145 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=150 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score	-0.37 score on a scale Standard Error 0.08	-1.48 score on a scale Standard Error 0.08	-1.36 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=152 Participants 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 (24 Weeks Pooled Arm) n=145 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=147 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in 22-item Sino-nasal Outcome Test Scores	-9.06 score on a scale Standard Error 1.61	-30.42 score on a scale Standard Error 1.65	-29.79 score on a scale Standard Error 1.64

SECONDARY outcome

Timeframe: Baseline up to 52 weeks

Population: Analysis was performed on ITT population. Data for this outcome measure was planned to be collected and analyzed for the pooled population of participants receiving Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants 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 (24 Weeks Pooled Arm) n=295 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Rescue Treatment Use: Estimate of Percentage of Participants With Greater Than or Equal to (>=) 1 Event by Week 52 Obtained Using Kaplan-Meier Method SCS treatment	42.5 percentage of participants with event Interval 34.5 to 50.2	13.1 percentage of participants with event Interval 9.0 to 18.0	—
Rescue Treatment Use: Estimate of Percentage of Participants With Greater Than or Equal to (>=) 1 Event by Week 52 Obtained Using Kaplan-Meier Method NP surgery	28.3 percentage of participants with event Interval 21.2 to 35.7	5.5 percentage of participants with event Interval 2.9 to 9.4	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants 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 (24 Weeks Pooled Arm) n=145 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=150 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Total Symptom Score	-0.93 score on a scale Standard Error 0.20	-4.17 score on a scale Standard Error 0.20	-3.79 score on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=150 Participants 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 (24 Weeks Pooled Arm) n=142 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=145 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in the University of Pennsylvania Smell Identification Test Score	-0.78 score on a scale Standard Error 0.71	9.99 score on a scale Standard Error 0.73	9.53 score on a scale Standard Error 0.72

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants 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 (24 Weeks Pooled Arm) n=145 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=150 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Severity of Decreased/Loss of Smell	-0.18 score on a scale Standard Error 0.09	-1.49 score on a scale Standard Error 0.09	-1.29 score on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=150 Participants 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 (24 Weeks Pooled Arm) n=140 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=149 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund-Mackay Score	0.11 score on a scale Standard Error 0.37	-5.60 score on a scale Standard Error 0.37	-6.83 score on a scale Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=150 Participants 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 (24 Weeks Pooled Arm) n=289 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis	-1.39 centimeters Standard Error 0.24	-4.32 centimeters Standard Error 0.19	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=150 Participants 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 (24 Weeks Pooled Arm) n=143 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=146 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Visual Analogue Scale for Rhinosinusitis	-0.93 centimeters Standard Error 0.26	-4.39 centimeters Standard Error 0.26	-4.74 centimeters Standard Error 0.26

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on ITT population. Data for this outcome measure was planned to be analyzed for the combined population of participants who received dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants 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 (24 Weeks Pooled Arm) n=295 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Peak Inspiratory Flow (NPIF)	18.65 liters per minute Standard Error 3.95	55.29 liters per minute Standard Error 3.08	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on ITT population. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants 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 (24 Weeks Pooled Arm) n=295 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Rhinorrhea Daily Symptom Score	-0.40 score on a scale Standard Error 0.07	-0.99 score on a scale Standard Error 0.05	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants 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 (24 Weeks Pooled Arm) n=145 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=150 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Rhinorrhea Daily Symptom Score	-0.35 score on a scale Standard Error 0.07	-1.19 score on a scale Standard Error 0.07	-1.15 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: The analysis was performed on ITT population. Here, "overall number of participants analyzed" signifies participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants 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 (24 Weeks Pooled Arm) n=17 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=22 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period	547.56 milligrams Standard Deviation 665.40	282.38 milligrams Standard Deviation 243.15	389.68 milligrams Standard Deviation 502.61

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants 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 (24 Weeks Pooled Arm) n=17 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=22 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant	19.58 days Standard Deviation 17.67	10.71 days Standard Deviation 9.00	23.23 days Standard Deviation 55.23

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on a subset of participants which included all randomized participants with asthma and had available data for this outcome measure. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants 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 (24 Weeks Pooled Arm) n=176 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Changed From Baseline at Week 24 in Forced Expiratory Volume in 1 Second (FEV1) for Participants With Asthma	-0.05 liters Standard Error 0.05	0.17 liters Standard Error 0.04	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on a subset of participants which included all randomized participants with asthma and had available data for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants 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 (24 Weeks Pooled Arm) n=91 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=85 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Forced Expiratory Volume in 1 Second for Participants With Asthma	-0.18 liters Standard Error 0.05	0.10 liters Standard Error 0.05	0.06 liters Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on a subset of participants which included all randomized participants with asthma and had available data for this outcome measure. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants 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 (24 Weeks Pooled Arm) n=171 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) for Participants With Asthma	0.08 score on a scale Standard Error 0.09	-0.78 score on a scale Standard Error 0.07	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on a subset of participants which included all randomized participants with Asthma and had available data for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants 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 (24 Weeks Pooled Arm) n=89 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=82 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Asthma Control Questionnaire-6 for Participants With Asthma	0.12 score on a scale Standard Error 0.10	-0.76 score on a scale Standard Error 0.10	-0.83 score on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on a subset of participants which included all randomized participants with asthma.

NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants 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 (24 Weeks Pooled Arm) n=176 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma	-0.39 score on a scale Standard Error 0.09	-1.36 score on a scale Standard Error 0.07	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on a subset of participants which included all randomized 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.

Outcome measures

Outcome measures
Measure	Placebo n=91 Participants 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 (24 Weeks Pooled Arm) n=91 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=85 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma	-0.34 score on a scale Standard Error 0.09	-1.51 score on a scale Standard Error 0.09	-1.44 score on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on a subset of participants which included all randomized participants with prior NP surgery history.

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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 (24 Weeks Pooled Arm) n=173 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery	-0.27 score on a scale Standard Error 0.10	-1.30 score on a scale Standard Error 0.08	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on a subset of participants which included all randomized participants with prior NP surgery history.

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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 (24 Weeks Pooled Arm) n=85 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=88 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery	-0.25 score on a scale Standard Error 0.10	-1.54 score on a scale Standard Error 0.10	-1.35 score on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on a subset of participants which included all randomized participants with asthma and had available data for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants 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 (24 Weeks Pooled Arm) n=176 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Asthma	0.13 score on a scale Standard Error 0.17	-1.88 score on a scale Standard Error 0.13	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on a subset of participants which included all randomized participants with asthma and had available data for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants 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 (24 Weeks Pooled Arm) n=91 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=85 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Asthma	0.29 score on a scale Standard Error 0.20	-2.25 score on a scale Standard Error 0.20	-2.34 score on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on a subset of participants which included all randomized participants with prior NP surgery history and had available data for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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 (24 Weeks Pooled Arm) n=172 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery	0.22 score on a scale Standard Error 0.19	-1.73 score on a scale Standard Error 0.15	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on a subset of participants which included all randomized participants with prior NP surgery history and had available data for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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 (24 Weeks Pooled Arm) n=85 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=87 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery	0.21 score on a scale Standard Error 0.21	-2.22 score on a scale Standard Error 0.22	-2.56 score on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on a subset of participants which included all randomized participants with asthma and had available data for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants 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 (24 Weeks Pooled Arm) n=174 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma	-0.33 score on a scale Standard Error 0.40	-5.86 score on a scale Standard Error 0.31	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on a subset of participants which included all randomized participants with asthma and had available data for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants 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 (24 Weeks Pooled Arm) n=89 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=85 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma	-0.20 score on a scale Standard Error 0.46	-6.23 score on a scale Standard Error 0.45	-7.22 score on a scale Standard Error 0.47

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on a subset of participants which included all randomized participants with prior NP surgery history and had available data for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants 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 (24 Weeks Pooled Arm) n=169 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery	-0.10 score on a scale Standard Error 0.42	-5.42 score on a scale Standard Error 0.33	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on a subset of participants which included all randomized participants with prior NP surgery history and had available data for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants 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 (24 Weeks Pooled Arm) n=82 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=87 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery	-0.06 score on a scale Standard Error 0.50	-6.01 score on a scale Standard Error 0.50	-7.45 score on a scale Standard Error 0.49

SECONDARY outcome

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

Population: Analysis was performed on safety population which included all participants who received at least 1 dose or part of a dose of the investigational medicinal product (IMP), analyzed according to the treatment actually received.

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.

Outcome measures

Outcome measures
Measure	Placebo n=150 Participants 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 (24 Weeks Pooled Arm) n=148 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=149 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation Any TEAE	138 Participants	134 Participants	125 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation Any treatment emergent SAE	16 Participants	12 Participants	8 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation Any TEAE leading to death	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation TEAE leading to treatment discontinuation	17 Participants	2 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure. Data for this outcome measure was planned to be analyzed for the combined population of participants who received Dupilumab.

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.

Outcome measures

Outcome measures
Measure	Placebo n=151 Participants 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 (24 Weeks Pooled Arm) n=289 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in European Quality of Life 5 Dimension Scale (EQ-5D) Visual Analog Scale Score	3.91 score on a scale Standard Error 1.50	10.83 score on a scale Standard Error 1.16	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

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).

Outcome measures

Outcome measures
Measure	Placebo n=151 Participants 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 (24 Weeks Pooled Arm) n=143 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=146 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 52 in European Quality of Life 5 Dimension Scale Visual Analog Scale Score	1.38 score on a scale Standard Error 1.60	11.98 score on a scale Standard Error 1.63	13.14 score on a scale Standard Error 1.62

SECONDARY outcome

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

Population: Analysis performed on pharmacokinetics population (PK) which included all participants who received at least 1 dose of IMP with at least 1 evaluable functional dupilumab concentration result. Here, 'number analyzed' = number of participants with available data for each time point. PK data was not collected and assessed for the placebo arm.

Outcome measures

Outcome measures
Measure	Placebo n=146 Participants 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 (24 Weeks Pooled Arm) n=149 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Functional Dupilumab Concentration in Serum Baseline	0.00 nanogram/milliliter Standard Deviation 0.00	0.00 nanogram/milliliter Standard Deviation 0.00	—
Functional Dupilumab Concentration in Serum Week 2	21545.79 nanogram/milliliter Standard Deviation 9120.36	22285.67 nanogram/milliliter Standard Deviation 8459.01	—
Functional Dupilumab Concentration in Serum Week 4	33760.62 nanogram/milliliter Standard Deviation 16419.72	37326.31 nanogram/milliliter Standard Deviation 14226.12	—
Functional Dupilumab Concentration in Serum Week 16	70503.07 nanogram/milliliter Standard Deviation 31234.86	74382.04 nanogram/milliliter Standard Deviation 33118.68	—
Functional Dupilumab Concentration in Serum Week 24	75929.41 nanogram/milliliter Standard Deviation 35466.00	79890.06 nanogram/milliliter Standard Deviation 35361.97	—
Functional Dupilumab Concentration in Serum Week 40	21052.06 nanogram/milliliter Standard Deviation 18588.68	80526.37 nanogram/milliliter Standard Deviation 34048.41	—
Functional Dupilumab Concentration in Serum Week 52	17276.13 nanogram/milliliter Standard Deviation 16353.20	75872.58 nanogram/milliliter Standard Deviation 34127.85	—
Functional Dupilumab Concentration in Serum Week 64	53.60 nanogram/milliliter Standard Deviation 160.53	851.30 nanogram/milliliter Standard Deviation 2682.21	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: The analysis was performed on ADA population which included participants who received at least 1 dose of IMP with at least one evaluable ADA serum sample that was assayed successfully in the ADA assay (either 'ADA negative' or 'ADA positive') following the first dose of the study medication.

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.

Outcome measures

Outcome measures
Measure	Placebo n=149 Participants 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 (24 Weeks Pooled Arm) n=148 Participants Pooled arm consisted of all participants from both dupilumab treatment arms up to 24 weeks as both arms to this time point used the 300 mg q2w regimen.	Dupilumab 300 mg q2w n=148 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies Response (ADA) With treatment-emergent ADA	6 Participants	18 Participants	8 Participants
Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies Response (ADA) With treatment-boosted ADA	1 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 16 serious events

Other events: 111 other events

Deaths: 0 deaths

Dupilumab 300 mg q2w Then q4w

Serious events: 12 serious events

Other events: 95 other events

Deaths: 1 deaths

Dupilumab 300 mg q2w

Serious events: 8 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER