Trial Outcomes & Findings for Dupilumab in Allergic Fungal Rhinosinusitis (AFRS) (LIBERTY-AFRS-AI) (NCT NCT04684524)

NCT ID: NCT04684524

Last Updated: 2025-12-22

Results Overview

The LMK score is used to quantify the degree of opacification of each sinus on CT scan. The CT scan LMK staging system represents the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus plus the osteomeatal complex on each side). The extent of sinus opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the osteomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is 12 per side; total score ranges from 0 (normal) to 24 (more opacified) corresponding to the sum of all sinuses and the osteomeatal complexes bilaterally. Higher score indicate worse outcome; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 62 participants
• Primary outcome timeframe: Baseline (Day 1) and Week 52
• Results posted on: 2025-12-22

Participant Flow

This study was conducted at 45 centers in 9 countries. A total of 152 participants were screened from 01-Dec-2020 to 28-Nov-2023 of which 90 were screen failures. Screen failures were mainly due to not meeting eligibility criteria.

A total of 62 participants were randomized in a 1:1 ratio to receive either dupilumab or matching placebo in this study. Reasons for study discontinuation are presented.

Participant milestones

Measure	Placebo Participants received placebo matched to dupilumab via subcutaneous (SC) injection for 52 weeks.	Dupilumab Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 milligrams (mg) every 2 weeks (q2w) for all adults and adolescents/children weighing \>=60 kilograms (kg) * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg every 4 weeks (q4w) for adolescents/children weighing \>=15 kg and \<30 kg.
Overall Study STARTED	29	33
Overall Study Randomized and Treated	28	33
Overall Study COMPLETED	21	29
Overall Study NOT COMPLETED	8	4

Reasons for withdrawal

Measure	Placebo Participants received placebo matched to dupilumab via subcutaneous (SC) injection for 52 weeks.	Dupilumab Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 milligrams (mg) every 2 weeks (q2w) for all adults and adolescents/children weighing \>=60 kilograms (kg) * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg every 4 weeks (q4w) for adolescents/children weighing \>=15 kg and \<30 kg.
Overall Study Other	2	0
Overall Study Withdrawal by Subject	5	3
Overall Study Adverse Event	1	1

Baseline Characteristics

Dupilumab in Allergic Fungal Rhinosinusitis (AFRS) (LIBERTY-AFRS-AI)

Baseline characteristics by cohort

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.	Total n=62 Participants Total of all reporting groups
Age, Continuous	37.4 years STANDARD_DEVIATION 14.0 • n=18 Participants	41.9 years STANDARD_DEVIATION 17.5 • n=102 Participants	39.8 years STANDARD_DEVIATION 16.0 • n=30 Participants
Sex: Female, Male Female	4 Participants n=18 Participants	13 Participants n=102 Participants	17 Participants n=30 Participants
Sex: Female, Male Male	25 Participants n=18 Participants	20 Participants n=102 Participants	45 Participants n=30 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants
Race (NIH/OMB) Asian	13 Participants n=18 Participants	12 Participants n=102 Participants	25 Participants n=30 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants
Race (NIH/OMB) Black or African American	3 Participants n=18 Participants	5 Participants n=102 Participants	8 Participants n=30 Participants
Race (NIH/OMB) White	12 Participants n=18 Participants	15 Participants n=102 Participants	27 Participants n=30 Participants
Race (NIH/OMB) More than one race	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=18 Participants	1 Participants n=102 Participants	2 Participants n=30 Participants
Lund Mackay (LMK) score	18.4 score on a scale STANDARD_DEVIATION 3.4 • n=18 Participants	17.5 score on a scale STANDARD_DEVIATION 3.8 • n=102 Participants	17.9 score on a scale STANDARD_DEVIATION 3.6 • n=30 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 52

Population: The intent-to-treat (ITT) population included all randomized participants.

The LMK score is used to quantify the degree of opacification of each sinus on CT scan. The CT scan LMK staging system represents the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus plus the osteomeatal complex on each side). The extent of sinus opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the osteomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is 12 per side; total score ranges from 0 (normal) to 24 (more opacified) corresponding to the sum of all sinuses and the osteomeatal complexes bilaterally. Higher score indicate worse outcome; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 52 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score	-1.81 score on a scale Standard Error 0.81	-9.17 score on a scale Standard Error 0.74

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1) and Week 24

Population: The ITT population included all randomized participants.

The nasal symptom diary is designed to assess the severity of chronic rhinosinusitis (CRS) nasal symptoms on daily basis. Score range: 0 = no symptoms, 1 = mild symptoms (symptoms clearly present, but minimal awareness and easily tolerated), 2= moderate symptoms (definite awareness of symptoms that is bothersome but tolerable) and 3 = severe symptoms (symptoms that are hard to tolerate, cause interference with activities or daily living). Higher scores denote greater symptom severity; a negative change from baseline indicate improvement. Baseline was defined as the average of the scores in the 7 days prior to the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 24 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary	-0.43 score on a scale Standard Error 0.13	-1.30 score on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The ITT population included all randomized participants.

The bilateral endoscopy NPS is determined by the clinician who assesses nasal polyp formation. Polyps on each side of the nose are graded based on polyp size; scores: 0 = no polyps; 1 = small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; 2 = polyps reaching below the lower border of the middle turbinate; 3 = large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate and 4 = large polyps causing complete obstruction. The total score is the sum of the right and left nostrils, ranging from 0 (no obstruction) to 8 (complete obstruction); higher score indicating worse outcome; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 24 in Endoscopy Nasal Polyp Score (NPS)	-0.80 score on a scale Standard Error 0.38	-3.16 score on a scale Standard Error 0.34

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The ITT population included all randomized participants.

The LMK score is used to quantify the degree of opacification of each sinus on CT scan. The CT scan LMK staging system represents the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus plus the osteomeatal complex on each side). The extent of sinus opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the osteomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is 12 per side; total score ranges from 0 (normal) to 24 (more opacified) corresponding to the sum of all sinuses and the osteomeatal complexes bilaterally. Higher score indicate worse outcome; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 24 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score	-1.93 score on a scale Standard Error 0.82	-7.38 score on a scale Standard Error 0.80

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1) and Week 24

Population: The ITT population included all randomized participants.

The nasal symptom diary is designed to assess the severity of CRS nasal symptoms on daily basis. The TSS is a composite score consisting of the sum of the following symptoms assessed daily in the morning: nasal congestion/obstruction, decreased/loss of sense of smell, rhinorrhea (average of anterior/posterior nasal discharge). Each of the individual items were scored from 0 = no symptoms to 3 = severe symptoms. TSS is the sum of individual items and ranges between 0 = no symptoms and 9 = severe symptoms. Higher scores on the TSS indicate greater symptom severity; a negative change from baseline indicate improvement. Baseline was defined as the average of the scores in the 7 days prior to the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 24 in Monthly Average Total Symptom Score (TSS) Derived From the Nasal Symptom Diary	-1.26 score on a scale Standard Error 0.35	-3.45 score on a scale Standard Error 0.31

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The ITT population included all randomized participants.

The UPSIT (UPSIT 40 odorant test) is a rapid and easy-to-administer method to quantitatively assess human olfactory function. The test consists of 4 booklets, each containing 10 odorants with 1 odorant per page. Above each odorant strip is a multiple-choice question with 4 alternative words to describe the odor and the participant is asked to indicate which word best describes the odor. Each smell has a possible of 4 answers with one being correct, therefore the potential total scores can range from 0 (worst possible score) to 40 (best possible score), with 1 point being awarded for each correctly identified odor. Scores of <=18 were classified as anosmia, 19 to 25 as severe microsmia, 26 to 30 as moderate microsmia, 31 to 34 as mild microsmia, and 35 to 40 as normal smell appreciation. Higher scores indicated better olfactory function; i.e. better sense of smell. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT)	4.41 score on a scale Standard Error 1.71	8.87 score on a scale Standard Error 1.60

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1) and Week 24

Population: The ITT population included all randomized participants.

The nasal symptom diary is designed to assess the severity of CRS nasal symptoms on daily basis. Decreased/loss of smell is scored as: 0 = no symptoms, 1 = mild symptoms (symptoms clearly present, but minimal awareness and easily tolerated), 2= moderate symptoms (definite awareness of symptoms that is bothersome but tolerable) and 3 = severe symptoms (symptoms that are hard to tolerate, cause interference with activities or daily living). Higher scores denote greater symptom severity; a negative change from baseline indicate improvement. Baseline was defined as the average of the scores in the 7 days prior to the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 24 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary	-0.39 score on a scale Standard Error 0.16	-1.28 score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

Population: The ITT population included all randomized participants.

The bilateral endoscopy NPS is determined by the clinician who assesses nasal polyp formation. Polyps on each side of the nose are graded based on polyp size; scores: 0 = no polyps; 1 = small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; 2 = polyps reaching below the lower border of the middle turbinate; 3 = large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate and 4 = large polyps causing complete obstruction. The total score is the sum of the right and left nostrils, ranging from 0 (no obstruction) to 8 (complete obstruction); higher score indicating worse outcome; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 52 in Endoscopy NPS	-0.55 score on a scale Standard Error 0.43	-3.32 score on a scale Standard Error 0.39

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1) and Week 52

Population: The ITT population included all randomized participants.

The nasal symptom diary is designed to assess the severity of CRS nasal symptoms on daily basis. Score range: 0 = no symptoms, 1 = mild symptoms (symptoms clearly present, but minimal awareness and easily tolerated), 2= moderate symptoms (definite awareness of symptoms that is bothersome but tolerable) and 3 = severe symptoms (symptoms that are hard to tolerate, cause interference with activities or daily living). Higher scores denote greater symptom severity; a negative change from baseline indicate improvement. Baseline was defined as the average of the scores in the 7 days prior to the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 52 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary	-0.17 score on a scale Standard Error 0.15	-1.57 score on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at baseline and Week 52 are reported.

The SNOT-22 is a validated questionnaire designed to assess the impact of CRS on participants health-related quality of life (HRQoL) and has 22 items covering symptoms, social/emotional impact, productivity, and sleep consequences of CRS. The recall period is past 2 weeks. Each item is rated on a 6-point Likert scale; response options ranging from 0 = no problem to 5 = problem as bad as it can be. A global score ranging from 0 (no impact) to 110 (severe impact) is calculated by summing the responses to all items; higher score indicates greater rhinosinusitis-related health burden; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=28 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 52 in 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score	-12.64 score on a scale Standard Error 4.06	-29.94 score on a scale Standard Error 3.75

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

Population: The ITT population included all randomized participants.

This method is used to calculate the percent occupied by disease. It is performed at locations including ethmoid sinus, frontal sinus, maxillary sinus, and sphenoid sinus. The total volume occupied by disease in all sinuses is reported here. For the analysis, central reading at baseline was used for comparison with Week 52 reading. It is graded on a scale of 0-100%; a higher score is worse and indicates greater volume occupied by disease. A negative change from baseline indicated improvement. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 52 in Three-dimensional CT Total Volume Occupied by Disease in All Sinuses	-5.73 percent Standard Error 3.91	-42.04 percent Standard Error 3.47

SECONDARY outcome

Timeframe: Week 52

Population: The ITT population included all randomized participants.

SCS use was defined as the use of SCS for rescue treatment of AFRS or for another reason and was captured by the Investigator (or designee) in electronic case report form (eCRF). Participants who underwent or planned to undergo surgery for AFRS were also recorded in eCRF.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Percentage of Participants Who Received Systemic Corticosteroids (SCS) and/or Underwent or Planned to Undergo Surgery for Allergic Fungal Rhinosinusitis (AFRS) at Week 52	31.0 percentage of particpants	3.0 percentage of particpants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The ITT population included all randomized participants. Only those participants with data collected at baseline and Week 24 are reported.

The SNOT-22 is a validated questionnaire designed to assess the impact of CRS on participants HRQoL and has 22 items covering symptoms, social/emotional impact, productivity, and sleep consequences of CRS. The recall period is past 2 weeks. Each item is rated on a 6-point Likert scale; response options ranging from 0 = no problem to 5 = problem as bad as it can be. A global score ranging from 0 (no impact) to 110 (severe impact) is calculated by summing the responses to all items; higher score indicates greater rhinosinusitis-related health burden; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=28 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 24 in SNOT-22 Total Score	-11.63 score on a scale Standard Error 4.02	-26.74 score on a scale Standard Error 3.81

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

Population: The safety population included all randomized participants who took at least 1 dose of study drug, regardless of the amount of treatment administered.

Blood samples were collected at specified timepoints for the assessment of IgE. Total IgE was measured with a quantitative method approved for diagnostic testing; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=28 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Percent Change From Baseline in Serum Total Immunoglobulin-E (IgE) to Week 52	6.91 percent change Standard Error 10.86	-73.81 percent change Standard Error 11.40

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1) and Weeks 24 and 52

Population: The ITT population included all randomized participants.

The nasal symptom diary is designed to assess the severity of CRS nasal symptoms on daily basis. Score range: 0 = no symptoms, 1 = mild symptoms (symptoms clearly present, but minimal awareness and easily tolerated), 2= moderate symptoms (definite awareness of symptoms that is bothersome but tolerable) and 3 = severe symptoms (symptoms that are hard to tolerate, cause interference with activities or daily living). Higher scores denote greater symptom severity; a negative change from baseline indicate improvement. Severity of rhinorrhea (average of anterior [runny nose]/posterior nasal discharge [post-nasal drip]) is presented here. Baseline was defined as the average of the scores in the 7 days prior to the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Weeks 24 and 52 in the Monthly Average Rhinorrhea Score From the Nasal Symptom Diary Week 24	-0.44 score on a scale Standard Error 0.13	-0.92 score on a scale Standard Error 0.12
Change From Baseline to Weeks 24 and 52 in the Monthly Average Rhinorrhea Score From the Nasal Symptom Diary Week 52	-0.33 score on a scale Standard Error 0.15	-1.09 score on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1) and Week 52

Population: The ITT population included all randomized participants.

The nasal symptom diary is designed to assess the severity of CRS nasal symptoms on daily basis. The TSS is a composite score consisting of the sum of the following symptoms assessed daily in the morning: nasal congestion/obstruction, decreased/loss of sense of smell, rhinorrhea (average of anterior/posterior nasal discharge). Each of the individual items were scored from 0 = no symptoms to 3 = severe symptoms. TSS is the sum of individual items and ranges between 0 = no symptoms and 9 = severe symptoms. Higher scores on the TSS indicate greater symptom severity; a negative change from baseline indicate improvement. Baseline was defined as the average of the scores in the 7 days prior to the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 52 in Monthly Average TSS Derived From the Nasal Symptom Diary	-0.71 score on a scale Standard Error 0.39	-4.10 score on a scale Standard Error 0.35

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 24 and 52

Population: The ITT population included all randomized participants. Only those participants with data collected at specified timepoints are reported.

The rhinosinusitis VAS is used to evaluate the overall severity of the rhinosinusitis. It is a recommended scale to determine the participant's disease severity and to guide the treatment for CRS. The participant is asked to answer the following question: "How troublesome are your symptoms of your rhinosinusitis" on a 10-centimeter VAS from 0 = not troublesome to 10 = worst thinkable troublesome. Based on their score on the VAS, the severity of rhinosinusitis is divided into 3 categories as follows: mild = VAS 0 to 3, moderate = VAS >3 to 7 and severe = VAS >7 to 10; higher score indicating worse outcome; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=28 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Weeks 24 and 52 in Visual Analog Scale (VAS) Rhinosinusitis Week 24	-1.29 score on a scale Standard Error 0.61	-4.30 score on a scale Standard Error 0.58
Change From Baseline to Weeks 24 and 52 in Visual Analog Scale (VAS) Rhinosinusitis Week 52	-1.20 score on a scale Standard Error 0.57	-5.52 score on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

Population: The ITT population included all randomized participants.

The UPSIT (UPSIT 40 odorant test) is a rapid and easy-to-administer method to quantitatively assess human olfactory function. The test consists of 4 booklets, each containing 10 odorants with 1 odorant per page. Above each odorant strip is a multiple-choice question with 4 alternative words to describe the odor and the participant is asked to indicate which word best describes the odor. Each smell has a possible of 4 answers with one being correct, therefore the potential total scores can range from 0 (worst possible score) to 40 (best possible score), with 1 point being awarded for each correctly identified odor. Scores of <=18 were classified as anosmia, 19 to 25 as severe microsmia, 26 to 30 as moderate microsmia, 31 to 34 as mild microsmia, and 35 to 40 as normal smell appreciation. Higher scores indicated better olfactory function, i.e. better sense of smell. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 52 in UPSIT	2.12 score on a scale Standard Error 1.73	9.45 score on a scale Standard Error 1.57

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1) and Week 52

Population: The ITT population included all randomized participants.

The nasal symptom diary is designed to assess the severity of CRS nasal symptoms on daily basis. Decreased/loss of smell is scored as: 0 = no symptoms, 1 = mild symptoms (symptoms clearly present, but minimal awareness and easily tolerated), 2= moderate symptoms (definite awareness of symptoms that is bothersome but tolerable) and 3 = severe symptoms (symptoms that are hard to tolerate, cause interference with activities or daily living). Higher scores denote greater symptom severity; a negative change from baseline indicate improvement. Baseline was defined as the average of the scores in the 7 days prior to the first dose of study drug.

Outcome measures

Measure	Placebo n=29 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Change From Baseline to Week 52 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary	-0.24 score on a scale Standard Error 0.17	-1.41 score on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: From first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks

Population: The safety population included all randomized participants who took at least 1 dose of study drug, regardless of the amount of treatment administered.

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was a medically important event. TEAEs were AEs that developed, worsened or became serious during the treatment-emergent period.

Outcome measures

Measure	Placebo n=28 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=33 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TEAEs	22 Participants	23 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TESAEs	3 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 12, 24 and 52

Population: The pharmacokinetic (PK) population included all participants in the safety population with at least 1 post-baseline PK result. Only those participants with data collected at specified timepoints are reported.

Blood samples were collected at the specified timepoints to obtain serum concentration of dupilumab.

Outcome measures

Measure	Placebo n=19 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Serum Concentration of Dupilumab Over Time Day 1	0.00 nanogram/milliliter Standard Deviation 0.00	—
Serum Concentration of Dupilumab Over Time Week 52	57284.21 nanogram/milliliter Standard Deviation 27401.32	—
Serum Concentration of Dupilumab Over Time Week 12	47750.00 nanogram/milliliter Standard Deviation 17828.70	—
Serum Concentration of Dupilumab Over Time Week 24	49597.78 nanogram/milliliter Standard Deviation 26542.80	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

Population: The safety population included all randomized participants who took at least 1 dose of study intervention, regardless of the amount of treatment administered. Only those participants with data collected at Baseline and Week 52 are reported.

Blood samples were collected at specified timepoints for the assessment of fungal-specific IgE which was measured with a quantitative method approved for diagnostic testing; a negative change from baseline indicated improvement. Baseline was defined as the last available value before the first dose of study drug.

Outcome measures

Measure	Placebo n=15 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=13 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Percent Change From Baseline in Fungal-specific IgE at Week 52 A. fumigatus Antigen IgE Antibody (AB)	-65.79 percent change	-77.20 percent change Standard Deviation 9.00
Percent Change From Baseline in Fungal-specific IgE at Week 52 F. proliferatum Antigen IgE AB	-20.18 percent change Standard Deviation 38.03	-66.09 percent change Standard Deviation 16.88
Percent Change From Baseline in Fungal-specific IgE at Week 52 C. lunata Antigen IgE AB	1.56 percent change Standard Deviation 29.80	-74.82 percent change Standard Deviation 12.34
Percent Change From Baseline in Fungal-specific IgE at Week 52 S. rostrata Antigen IgE AB	28.89 percent change Standard Deviation 52.58	-61.77 percent change Standard Deviation 14.37
Percent Change From Baseline in Fungal-specific IgE at Week 52 C. albicans Antigen IgE AB	15.69 percent change Standard Deviation 33.17	-63.60 percent change Standard Deviation 17.06
Percent Change From Baseline in Fungal-specific IgE at Week 52 B. spicifera Antigen IgE AB	19.12 percent change Standard Deviation 52.10	-56.26 percent change Standard Deviation 22.36
Percent Change From Baseline in Fungal-specific IgE at Week 52 A. niger Antigen IgE AB	2.46 percent change Standard Deviation 55.43	-67.48 percent change Standard Deviation 13.72
Percent Change From Baseline in Fungal-specific IgE at Week 52 A. flavus Antigen IgE AB	0.75 percent change Standard Deviation 44.77	-52.94 percent change Standard Deviation 19.62
Percent Change From Baseline in Fungal-specific IgE at Week 52 A. tenuis alternata Antigen IgE AB	16.06 percent change Standard Deviation 47.96	-56.07 percent change Standard Deviation 21.78
Percent Change From Baseline in Fungal-specific IgE at Week 52 Mould Mix 2 IgE	-17.50 percent change Standard Deviation 29.93	-66.81 percent change Standard Deviation 20.86

SECONDARY outcome

Timeframe: From first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks

Population: The ADA population included all participants from the safety population with at least 1 post-baseline ADA result (positive, negative or inconclusive).

Plasma samples were collected to evaluate antibodies to dupilumab. Treatment-emergent ADA responses were defined as a positive response in the ADA assay post first dose, when baseline results were negative or missing.

Outcome measures

Measure	Placebo n=19 Participants Participants received placebo matched to dupilumab via SC injection for 52 weeks.	Dupilumab n=22 Participants Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Dupilumab	0 Participants	1 Participants

Adverse Events

Dupilumab

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dupilumab n=33 participants at risk Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.	Placebo n=28 participants at risk Participants received placebo matched to dupilumab via SC injection for 52 weeks.
Infections and infestations Infection	0.00% 0/33 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	3.6% 1/28 • Number of events 1 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Respiratory, thoracic and mediastinal disorders Allergic Fungal Rhinosinusitis	0.00% 0/33 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	7.1% 2/28 • Number of events 2 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Renal and urinary disorders Ureterolithiasis	0.00% 0/33 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	3.6% 1/28 • Number of events 1 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.

Other adverse events

Measure	Dupilumab n=33 participants at risk Participants received dupilumab depending on the weight at screening via SC injection for 52 weeks as follows: * 300 mg q2w for all adults and adolescents/children weighing \>=60 kg * 200 mg q2w for adolescents/children weighing \>=30 kg and \<60 kg * 300 mg q4w for adolescents/children weighing \>=15 kg and \<30 kg.	Placebo n=28 participants at risk Participants received placebo matched to dupilumab via SC injection for 52 weeks.
Infections and infestations Suspected Covid-19	6.1% 2/33 • Number of events 2 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	0.00% 0/28 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Nervous system disorders Headache	6.1% 2/33 • Number of events 2 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	0.00% 0/28 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Respiratory, thoracic and mediastinal disorders Allergic Fungal Rhinosinusitis	3.0% 1/33 • Number of events 1 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	21.4% 6/28 • Number of events 7 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/33 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	7.1% 2/28 • Number of events 4 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Respiratory, thoracic and mediastinal disorders Epistaxis	12.1% 4/33 • Number of events 4 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	3.6% 1/28 • Number of events 1 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Gastrointestinal disorders Abdominal Pain	6.1% 2/33 • Number of events 2 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	0.00% 0/28 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Gastrointestinal disorders Diarrhoea	6.1% 2/33 • Number of events 2 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	0.00% 0/28 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/33 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	7.1% 2/28 • Number of events 2 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Investigations Alanine Aminotransferase Increased	6.1% 2/33 • Number of events 2 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	3.6% 1/28 • Number of events 1 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Injury, poisoning and procedural complications Accidental Overdose	9.1% 3/33 • Number of events 3 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	14.3% 4/28 • Number of events 5 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Injury, poisoning and procedural complications Thermal Burn	0.00% 0/33 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	7.1% 2/28 • Number of events 2 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.
Infections and infestations Covid-19	15.2% 5/33 • Number of events 5 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.	14.3% 4/28 • Number of events 4 • Adverse events and deaths were assessed from first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks Analysis was performed on the safety population.

Additional Information

Trial Transparency Team

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Phone: 800-633-1610

Email: Contact-US@sanofi.com

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