Trial Outcomes & Findings for A Controlled Clinical Study of Dupilumab in Patients With Bilateral Nasal Polyps (NCT NCT02912468)

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

276 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2019-07-25

Participant Flow

Participants were involved in the study from 05 December 2016 to 05 July 2018 at 67 active centers in 13 countries. A total of 506 participants were screened, of which 276 participants were enrolled and randomized to receive dupilumab 300 mg or placebo. A total of 230 participants failed screening mainly due to failure to meet inclusion criteria.

Randomization was stratified by the presence of comorbid asthma and/or non-steroidal anti-inflammatory drug exacerbated respiratory disease (NSAID-ERD), prior nasal polyposis (NP) surgery (yes or no), 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 24 added to background therapy of intranasal mometasone furoate nasal spray (MFNS) at stable dose.	Dupilumab 300 mg Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Overall Study STARTED	133	143
Overall Study Treated	133	142
Overall Study Safety Population	132	143
Overall Study COMPLETED	124	138
Overall Study NOT COMPLETED	9	5

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 24 added to background therapy of intranasal mometasone furoate nasal spray (MFNS) at stable dose.	Dupilumab 300 mg Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Overall Study Adverse Event	3	2
Overall Study Withdrawal by Subject	6	2
Overall Study Randomized and not treated	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Total n=276 Participants Total of all reporting groups
Age, Continuous	50.83 Years STANDARD_DEVIATION 13.21 • n=133 Participants	50.17 Years STANDARD_DEVIATION 13.59 • n=143 Participants	50.49 Years STANDARD_DEVIATION 13.39 • n=276 Participants
Sex: Female, Male Female	63 Participants n=133 Participants	55 Participants n=143 Participants	118 Participants n=276 Participants
Sex: Female, Male Male	70 Participants n=133 Participants	88 Participants n=143 Participants	158 Participants n=276 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=131 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	5 Participants n=143 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	6 Participants n=274 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.
Ethnicity (NIH/OMB) Not Hispanic or Latino	130 Participants n=131 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	138 Participants n=143 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	268 Participants n=274 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=131 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	0 Participants n=143 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	0 Participants n=274 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=133 Participants	1 Participants n=143 Participants	1 Participants n=276 Participants
Race (NIH/OMB) Asian	0 Participants n=133 Participants	1 Participants n=143 Participants	1 Participants n=276 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=133 Participants	0 Participants n=143 Participants	0 Participants n=276 Participants
Race (NIH/OMB) Black or African American	7 Participants n=133 Participants	2 Participants n=143 Participants	9 Participants n=276 Participants
Race (NIH/OMB) White	126 Participants n=133 Participants	138 Participants n=143 Participants	264 Participants n=276 Participants
Race (NIH/OMB) More than one race	0 Participants n=133 Participants	0 Participants n=143 Participants	0 Participants n=276 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=133 Participants	1 Participants n=143 Participants	1 Participants n=276 Participants
Nasal Congestion/Obstruction (NC) Symptom Severity Score	2.45 score on a scale STANDARD_DEVIATION 0.55 • n=133 Participants	2.26 score on a scale STANDARD_DEVIATION 0.57 • n=143 Participants	2.35 score on a scale STANDARD_DEVIATION 0.57 • n=276 Participants
Nasal Polyp Score (NPS)	5.86 score on a scale STANDARD_DEVIATION 1.31 • n=132 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	5.64 score on a scale STANDARD_DEVIATION 1.23 • n=143 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	5.75 score on a scale STANDARD_DEVIATION 1.28 • n=275 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score	-0.45 score on a scale Standard Error 0.07	-1.34 score on a scale Standard Error 0.07

PRIMARY outcome

Timeframe: Baseline, Week 24

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=132 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Polyp Score	0.17 score on a scale Standard Error 0.15	-1.89 score on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The 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.

Outcome measures

Outcome measures
Measure	Placebo n=129 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=141 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund-Mackay (LMK) Score	-0.74 score on a scale Standard Error 0.37	-8.18 score on a scale Standard Error 0.34

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The analysis was performed on ITT population.

The TSS was the sum of participant-assessed nasal symptom scores for nasal congestion/obstruction, decreased/loss of sense of smell, and rhinorrhea (anterior/posterior nasal discharge), each accessed on 0-3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). Total score ranged from 0 (no symptoms) to 9 (severe symptoms). Higher score indicated more severe symptoms. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Total Symptom Score (TSS)	-1.17 score on a scale Standard Error 0.17	-3.77 score on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The analysis was performed on ITT. 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. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=140 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in the University of Pennsylvania Smell Identification Test (UPSIT) Score	0.70 score on a scale Standard Error 0.71	11.26 score on a scale Standard Error 0.67

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The 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. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily	-0.29 score on a scale Standard Error 0.07	-1.41 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The 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 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.

Outcome measures

Outcome measures
Measure	Placebo n=131 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=137 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in 22-item Sino-nasal Outcome Test (SNOT-22) Scores	-9.31 score on a scale Standard Error 1.62	-30.43 score on a scale Standard Error 1.54

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: The analysis was performed on ITT population.

Rescue treatment was defined as usage of systemic corticosteroids (SCS) or NP surgery (actual or planned) during the treatment period. Rescue treatment included: * SCS: Betamethasone, dexamethasone, dexamethasone sodium phosphate, Hydrocortisone sodium succinate, methylprednisolone, prednisolone, prednisolone metasulfobenzoate sodium, prednisone, and triamcinolone. * Sino-nasal surgery for nasal polyps when there was worsening of signs and/or symptoms during the study. Estimate of percentage of participants with event by Week 24 was obtained using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 24 Obtained Using Kaplan-Meier Method SCS treatment	18.9 percentage of participants with event Interval 12.7 to 26.0	6.5 percentage of participants with event Interval 3.2 to 11.5
Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 24 Obtained Using Kaplan-Meier Method NP surgery	7.5 percentage of participants with event Interval 3.7 to 13.2	2.1 percentage of participants with event Interval 0.6 to 5.6

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The 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 (cm) VAS the answer to the question, "How troublesome are your symptoms of your rhinosinusitis?" The range of the VAS was from 0 (not troublesome) to 10 (worse thinkable troublesome), where higher score indicated worse thinkable troublesome. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=130 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=136 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis	-1.34 centimeters Standard Error 0.24	-4.54 centimeters Standard Error 0.23

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The analysis was performed on ITT population.

NPIF evaluation represented a physiologic measure of the air flow through both nasal cavities during forced inspiration expressed in liters per minute. Higher NPIF values are indicative of better nasal air flow. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Peak Inspiratory Flow (NPIF)	14.09 liters per minute Standard Error 3.97	54.50 liters per minute Standard Error 3.73

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The 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 were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Rhinorrhea Daily Symptom Score	-0.42 score on a scale Standard Error 0.06	-1.04 score on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline, Week 24

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

FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=79 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=82 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Forced Expiratory Volume in 1 Second (FEV1) for Participants With Asthma	-0.06 liters Standard Error 0.05	0.15 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.

ACQ-6 had 6 questions which assessed the most common asthma symptoms (woken by asthma, symptoms on waking, activity limitation, shortness of breath, wheezing, puffs/inhalations use). Participants were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale ranged from 0 = no impairment to 6 = maximum impairment. The ACQ-6 score was the mean of the scores of all 6 questions and therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), with higher scores indicated lower asthma control. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with the corresponding baseline value, treatment group, prior surgery, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=76 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=75 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) Scores for Participants With Asthma	-0.24 score on a scale Standard Error 0.10	-1.00 score on a scale Standard Error 0.10

SECONDARY outcome

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

Population: The 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. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Nasal Congestion Symptom Severity Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 28	-0.48 score on a scale Standard Error 0.07	-1.36 score on a scale Standard Error 0.07
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Nasal Congestion Symptom Severity Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 32	-0.50 score on a scale Standard Error 0.07	-1.33 score on a scale Standard Error 0.07
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Nasal Congestion Symptom Severity Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 36	-0.53 score on a scale Standard Error 0.07	-1.05 score on a scale Standard Error 0.07
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Nasal Congestion Symptom Severity Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 40	-0.51 score on a scale Standard Error 0.08	-0.83 score on a scale Standard Error 0.07
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Nasal Congestion Symptom Severity Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 44	-0.49 score on a scale Standard Error 0.08	-0.77 score on a scale Standard Error 0.07
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Nasal Congestion Symptom Severity Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 48	-0.52 score on a scale Standard Error 0.08	-0.77 score on a scale Standard Error 0.07

SECONDARY outcome

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

Population: The 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 mean and SE were obtained from ANCOVA model.

Outcome measures

Outcome measures
Measure	Placebo n=132 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Weeks 36 and 48 in Nasal Polyp Score (Assessments Performed 12 and 24 Weeks After End of Treatment) Week 36	-0.06 score on a scale Standard Error 0.14	-0.99 score on a scale Standard Error 0.13
Change From Baseline at Weeks 36 and 48 in Nasal Polyp Score (Assessments Performed 12 and 24 Weeks After End of Treatment) Week 48	0.14 score on a scale Standard Error 0.13	-0.66 score on a scale Standard Error 0.12

SECONDARY outcome

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

Population: The 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 were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=129 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=141 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 48 in Opacification of Sinuses Measured by Lund-Mackay Score (Assessment Performed 24 Weeks After End of Treatment)	-0.82 score on a scale Standard Error 0.38	-2.62 score on a scale Standard Error 0.36

SECONDARY outcome

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

Population: The 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 were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Total Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 32	-1.25 score on a scale Standard Error 0.17	-3.64 score on a scale Standard Error 0.17
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Total Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 28	-1.18 score on a scale Standard Error 0.17	-3.84 score on a scale Standard Error 0.16
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Total Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 36	-1.31 score on a scale Standard Error 0.18	-2.91 score on a scale Standard Error 0.17
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Total Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 40	-1.27 score on a scale Standard Error 0.18	-2.28 score on a scale Standard Error 0.17
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Total Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 44	-1.20 score on a scale Standard Error 0.18	-2.09 score on a scale Standard Error 0.17
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Total Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 48	-1.28 score on a scale Standard Error 0.19	-2.05 score on a scale Standard Error 0.18

SECONDARY outcome

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

Population: The 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 were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=140 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 48 in University of Pennsylvania Smell Identification Test (Assessment Performed 24 Weeks After End of Treatment)	0.21 score on a scale Standard Error 0.77	4.20 score on a scale Standard Error 0.73

SECONDARY outcome

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

Population: The 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 were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily (Assessments Performed 4-24 Weeks After End of Treatment) Week 44	-0.28 score on a scale Standard Error 0.07	-0.74 score on a scale Standard Error 0.07
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily (Assessments Performed 4-24 Weeks After End of Treatment) Week 28	-0.28 score on a scale Standard Error 0.08	-1.45 score on a scale Standard Error 0.07
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily (Assessments Performed 4-24 Weeks After End of Treatment) Week 32	-0.31 score on a scale Standard Error 0.08	-1.36 score on a scale Standard Error 0.07
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily (Assessments Performed 4-24 Weeks After End of Treatment) Week 36	-0.33 score on a scale Standard Error 0.08	-1.07 score on a scale Standard Error 0.07
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily (Assessments Performed 4-24 Weeks After End of Treatment) Week 40	-0.30 score on a scale Standard Error 0.07	-0.83 score on a scale Standard Error 0.07
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily (Assessments Performed 4-24 Weeks After End of Treatment) Week 48	-0.30 score on a scale Standard Error 0.07	-0.71 score on a scale Standard Error 0.06

SECONDARY outcome

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

Population: The 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. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=131 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=137 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Weeks 36 and 48 in 22-item Sino-nasal Outcome Test Scores (Assessments Performed 12 and 24 Weeks After End of Treatment) Week 36	-8.31 score on a scale Standard Error 1.75	-20.87 score on a scale Standard Error 1.67
Change From Baseline at Weeks 36 and 48 in 22-item Sino-nasal Outcome Test Scores (Assessments Performed 12 and 24 Weeks After End of Treatment) Week 48	-8.36 score on a scale Standard Error 1.88	-17.66 score on a scale Standard Error 1.80

SECONDARY outcome

Timeframe: Baseline up to Week 48

Population: The analysis was performed on ITT population.

Rescue treatment was defined as usage of SCS or NP surgery (actual or planned) during the study. Rescue treatment included: * SCS: Betamethasone, dexamethasone, dexamethasone sodium phosphate, Hydrocortisone sodium succinate, methylprednisolone, prednisolone, prednisolone metasulfobenzoate sodium, prednisone, and triamcinolone. * Sino-nasal surgery for nasal polyps when there was worsening of signs and/or symptoms during the study. Estimate of percentage of participants with event by Week 48 was obtained using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 48 Obtained Using Kaplan-Meier Method SCS treatment	28.8 percentage of participants with event Interval 21.4 to 36.7	21.4 percentage of participants with event Interval 15.0 to 28.5
Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 48 Obtained Using Kaplan-Meier Method NP surgery	12.5 percentage of participants with event Interval 7.5 to 18.9	6.3 percentage of participants with event Interval 2.9 to 11.4

SECONDARY outcome

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

Population: The 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 cm VAS the answer to the question, "How troublesome are your symptoms of your rhinosinusitis?" The range of the VAS was from 0 (not troublesome) to 10 (worse thinkable troublesome), where higher score indicated worse thinkable troublesome. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=130 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=136 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Weeks 36 and 48 in Visual Analog Scale for Rhinosinusitis (Assessments Performed 12 and 24 Weeks After End of Treatment) Week 36	-1.36 centimeters Standard Error 0.26	-3.02 centimeters Standard Error 0.25
Change From Baseline at Weeks 36 and 48 in Visual Analog Scale for Rhinosinusitis (Assessments Performed 12 and 24 Weeks After End of Treatment) Week 48	-1.17 centimeters Standard Error 0.25	-2.42 centimeters Standard Error 0.24

SECONDARY outcome

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

Population: The 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 were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Rhinorrhea Daily Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 28	-0.42 score on a scale Standard Error 0.06	-1.04 score on a scale Standard Error 0.06
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Rhinorrhea Daily Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 32	-0.43 score on a scale Standard Error 0.06	-0.97 score on a scale Standard Error 0.06
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Rhinorrhea Daily Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 36	-0.44 score on a scale Standard Error 0.07	-0.80 score on a scale Standard Error 0.06
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Rhinorrhea Daily Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 40	-0.44 score on a scale Standard Error 0.07	-0.63 score on a scale Standard Error 0.06
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Rhinorrhea Daily Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 44	-0.41 score on a scale Standard Error 0.07	-0.58 score on a scale Standard Error 0.06
Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Rhinorrhea Daily Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) Week 48	-0.45 score on a scale Standard Error 0.07	-0.58 score on a scale Standard Error 0.07

SECONDARY outcome

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

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

FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=79 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=82 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 48 in Forced Expiratory Volume in 1 Second for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment)	-0.11 liters Standard Error 0.05	-0.05 liters Standard Error 0.05

SECONDARY outcome

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

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 the corresponding baseline value, treatment group, prior surgery, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=76 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=75 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 48 in Asthma Control Questionnaire-6 Scores for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment)	-0.09 score on a scale Standard Error 0.11	-0.55 score on a scale Standard Error 0.11

SECONDARY outcome

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

Population: The 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 study drug until 98 days following the last administration of study drug. Serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.

Outcome measures

Outcome measures
Measure	Placebo n=132 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation Any TEAE	93 Participants	93 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation Any treatment emergent SAE	19 Participants	6 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	3 Participants	5 Participants

SECONDARY outcome

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

Population: Analysis performed on pharmacokinetic population, which included participants who received atleast 1 dose of IMP with atleast 1 evaluable functional IMP concentration. Here, 'number analyzed'=number of participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for placebo

Outcome measures

Outcome measures
Measure	Placebo n=142 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Functional Dupilumab Concentration in Serum Baseline	0.00 nanogram/milliliter Standard Deviation 0.00	—
Functional Dupilumab Concentration in Serum Week 4	31267.18 nanogram/milliliter Standard Deviation 13008.16	—
Functional Dupilumab Concentration in Serum Week 8	48306.73 nanogram/milliliter Standard Deviation 20621.18	—
Functional Dupilumab Concentration in Serum Week 16	63958.12 nanogram/milliliter Standard Deviation 29822.30	—
Functional Dupilumab Concentration in Serum Week 24	69224.11 nanogram/milliliter Standard Deviation 36933.70	—
Functional Dupilumab Concentration in Serum Week 36	356.53 nanogram/milliliter Standard Deviation 1501.69	—
Functional Dupilumab Concentration in Serum Week 48	39.00 nanogram/milliliter Standard Deviation 0.00	—

SECONDARY outcome

Timeframe: Baseline to End of study (Week 48)

Population: The analysis was performed on ADA population which included participants who received at least 1 dose of IMP with at least one non-missing ADA assay result 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=132 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response With treatment-emergent ADA	7 Participants	22 Participants
Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response With treatment-boosted ADA	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Week 24

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

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

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=9 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period	366.07 milligrams Standard Deviation 247.07	686.65 milligrams Standard Deviation 1575.86

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: The 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=25 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=9 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant	11.04 days Standard Deviation 6.79	23.33 days Standard Deviation 50.13

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The 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. 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=130 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=136 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in European Quality of Life 5 Dimension (EQ-5D) Visual Analog Scale Score	1.74 score on a scale Standard Error 1.54	12.00 score on a scale Standard Error 1.48

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.

Outcome measures

Outcome measures
Measure	Placebo n=79 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=82 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Congestion Symptom Severity Score: Subgroup of Participants With Asthma	-0.36 score on a scale Standard Error 0.09	-1.48 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, asthma/NSAID-ERD status, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=99 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=99 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Congestion Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery	-0.52 score on a scale Standard Error 0.09	-1.41 score on a scale Standard Error 0.08

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.

Outcome measures

Outcome measures
Measure	Placebo n=78 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=82 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Asthma	0.27 score on a scale Standard Error 0.20	-1.89 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.

Outcome measures

Outcome measures
Measure	Placebo n=98 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=99 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery	0.14 score on a scale Standard Error 0.18	-1.86 score on a scale Standard Error 0.18

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 were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=78 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=81 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma	-0.15 score on a scale Standard Error 0.47	-7.97 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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=98 Participants Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery	-0.39 score on a scale Standard Error 0.42	-7.60 score on a scale Standard Error 0.41

Adverse Events

Placebo

Serious events: 19 serious events

Other events: 61 other events

Deaths: 0 deaths

Dupilumab 300 mg

Serious events: 6 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=132 participants at risk Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 participants at risk Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
General disorders Injection Site Erythema	9.1% 12/132 • Number of events 30 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	5.6% 8/143 • Number of events 25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Infections and infestations Bronchitis	6.1% 8/132 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Infections and infestations Nasopharyngitis	15.2% 20/132 • Number of events 25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	13.3% 19/143 • Number of events 25 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Nervous system disorders Headache	8.3% 11/132 • Number of events 13 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	4.9% 7/143 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Asthma	6.1% 8/132 • Number of events 11 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	2.1% 3/143 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Cough	5.3% 7/132 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	2.8% 4/143 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.0% 4/132 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	7.7% 11/143 • Number of events 13 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Nasal Polyps	12.9% 17/132 • Number of events 26 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	11.2% 16/143 • Number of events 17 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.

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

Measure	Placebo n=132 participants at risk Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.	Dupilumab 300 mg n=143 participants at risk Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/132 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.70% 1/143 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Cardiac disorders Aortic Valve Stenosis	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Eye disorders Vitreous Haemorrhage	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Immune system disorders Eosinophilic Granulomatosis With Polyangiitis	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.70% 1/143 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Infections and infestations Acute Sinusitis	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Infections and infestations Erysipelas	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Infections and infestations Pneumonia	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Injury, poisoning and procedural complications Clavicle Fracture	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Foot Deformity	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anal Cancer	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Nervous system disorders Carpal Tunnel Syndrome	0.00% 0/132 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.70% 1/143 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Nervous system disorders Lumbar Radiculopathy	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Reproductive system and breast disorders Uterine Polyp	0.00% 0/132 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.70% 1/143 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Asthma	1.5% 2/132 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Chronic Rhinosinusitis With Nasal Polyps	0.76% 1/132 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	0.00% 0/143 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Nasal Polyps	5.3% 7/132 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.	1.4% 2/143 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of study regardless of seriousness or relationship to investigational product. Time frame for reporting of TEAE was up to 36 weeks. Reported AEs are treatment emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration to the last study drug administration + 98 days). Analysis was performed on safety population.