Allergic Fungal Rhinosinusitis
Conditions
Brief summary
Primary Objective: * To evaluate the efficacy of treatment with dupilumab to reduce sinus opacification in a population with allergic fungal rhinosinusitis (AFRS) Secondary Objectives: * To evaluate the efficacy of treatment with dupilumab to reduce sinus opacification in a population with allergic fungal rhinosinusitis (AFRS) at Week 24 * To assess the efficacy of dupilumab to reduce the need for rescue treatments * To evaluate the efficacy of treatment with dupilumab in improving symptoms in AFRS * To evaluate the efficacy of dupilumab to reduce nasal polyp formation in participants with AFRS * To evaluate the efficacy of dupilumab in improving overall symptom severity and quality of life in AFRS * To evaluate the efficacy of dupilumab in improving sense of smell in participants with AFRS * To explore the effect of dupilumab as assessed by three-Dimensional CT volumetric measurement of the paranasal sinuses * To evaluate the safety and tolerability of dupilumab when administered to participants with AFRS * To evaluate the pharmacokinetics (PK) of dupilumab in participants with AFRS * To characterize the effect of dupilumab on total IgE and specific IgE * To assess immunogenicity to dupilumab in participants with AFRS
Detailed description
The duration of study for each participant will include 2-4 weeks of screening period (2 additional weeks could be allowed), 52 weeks of randomized investigational medicinal product (IMP) intervention period and 12 weeks of follow-up period.
Interventions
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
DRUGPlacebo
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Participant must be at least 6 years of age (or the minimum legal age for adolescents in the country of the investigational site) at the time of signing the informed consent. Participants with the diagnosis of AFRS adapted from criteria by Bent and Kuhn (meeting all): * IgE mediated inflammatory response to fungal hyphae (specific IgE serology or skin test) Evidence of sensitization to fungus by skin testing (at screening or documented historical positive skin test in the previous 12 months), or positive fungal-specific IgE in serum at screening. * Nasal polyposis confirmed by nasal endoscopy at screening. * Characteristic CT signs to be performed during screening period and can include any of the below signs as assessed by central reader: * hyperdensities * bony demineralization * bone erosion of sinus * Eosinophilic mucin/mucus identified within 5 years prior to screening or at screening with or without positive fungal stain AFRS patients with the following: * An endoscopic NPS of at least 2 out of 4 for unilateral polyps or 3 out of 8 for bilateral polyps at Visit 1 (central reading) and Visit 2 (local reading) and, * Sinus opacification in CT scan with an LMK score of 9 for patients with unilateral polyps or 12 for patients with bilateral polyps during screening period and, Body weight ≥15 kg
Exclusion criteria
* Patients with nasal conditions/concomitant nasal diseases making them non-evaluable at Visit 1 or for the primary efficacy * Nasal cavity malignant tumor and benign tumors. * Known of fungal invasion into sinus tissue. * Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study * Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated. * Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection * Known or suspected immunodeficiency * Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit 1 or during the screening period. * History of systemic hypersensitivity or anaphylaxis to dupilumab or any of its excipients. * Treatment with commercially available dupilumab within 12 months, participation in prior dupilumab clinical trial, or discontinued dupilumab use due to adverse event. * Patients who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as Xhance™, during screening period. * Patients who are on intranasal corticosteroids (INCS) spray unless they have received stable dose for at least 4 weeks prior to Visit 1. * Patients who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit 1. * Patients who have taken: * Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to Visit 1 * Any investigational mAb within 5 half-lives prior to Visit 1 * Anti-IgE therapy (omalizumab) within 4 months prior to Visit 1. - Treatment with a live (attenuated) vaccine within 4 weeks prior to Visit 1 * Leukotriene antagonists/modifiers unless patient is on a continuous treatment for at least 30 days prior to Visit 1. * Initiation of allergen immunotherapy within 3 months prior to Visit 1 or a plan to begin therapy or change its dose during the screening or treatment period. - Patients received SCS during screening period. - Either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to Screening Visit (Visit 1). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 52 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score | Baseline (Day 1) and Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Endoscopy Nasal Polyp Score (NPS) | Baseline (Day 1) and Week 24 | 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. |
| Change From Baseline to Week 24 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score | Baseline (Day 1) and Week 24 | 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. |
| Change From Baseline to Week 24 in Monthly Average Total Symptom Score (TSS) Derived From the Nasal Symptom Diary | Baseline (Day -7 to Day -1) and Week 24 | 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. |
| Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT) | Baseline (Day 1) and Week 24 | 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. |
| Change From Baseline to Week 24 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary | Baseline (Day -7 to Day -1) and Week 24 | 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. |
| Change From Baseline to Week 52 in Endoscopy NPS | Baseline (Day 1) and Week 52 | 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. |
| Change From Baseline to Week 52 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary | Baseline (Day -7 to Day -1) and Week 52 | 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. |
| Change From Baseline to Week 52 in 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score | Baseline (Day 1) and Week 52 | 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. |
| Change From Baseline to Week 52 in Three-dimensional CT Total Volume Occupied by Disease in All Sinuses | Baseline (Day 1) and Week 52 | 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. |
| Percentage of Participants Who Received Systemic Corticosteroids (SCS) and/or Underwent or Planned to Undergo Surgery for Allergic Fungal Rhinosinusitis (AFRS) at Week 52 | Week 52 | 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. |
| Change From Baseline to Week 24 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary | Baseline (Day -7 to Day -1) and Week 24 | 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. |
| Percent Change From Baseline in Serum Total Immunoglobulin-E (IgE) to Week 52 | Baseline (Day 1) and Week 52 | 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. |
| Change From Baseline to Weeks 24 and 52 in the Monthly Average Rhinorrhea Score From the Nasal Symptom Diary | Baseline (Day -7 to Day -1) and Weeks 24 and 52 | 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. |
| Change From Baseline to Week 52 in Monthly Average TSS Derived From the Nasal Symptom Diary | Baseline (Day -7 to Day -1) and Week 52 | 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. |
| Change From Baseline to Weeks 24 and 52 in Visual Analog Scale (VAS) Rhinosinusitis | Baseline (Day 1) and Weeks 24 and 52 | 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. |
| Change From Baseline to Week 52 in UPSIT | Baseline (Day 1) and Week 52 | 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. |
| Change From Baseline to Week 52 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary | Baseline (Day -7 to Day -1) and Week 52 | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | From first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks | 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. |
| Serum Concentration of Dupilumab Over Time | Baseline (Day 1) and Weeks 12, 24 and 52 | Blood samples were collected at the specified timepoints to obtain serum concentration of dupilumab. |
| Percent Change From Baseline in Fungal-specific IgE at Week 52 | Baseline (Day 1) and Week 52 | 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. |
| Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Dupilumab | From first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks | 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. |
| Change From Baseline to Week 24 in SNOT-22 Total Score | Baseline (Day 1) and Week 24 | 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. |
Countries
Argentina, Canada, China, India, Israel, Japan, Saudi Arabia, Turkey (Türkiye), United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to dupilumab via SC injection for 52 weeks. | 29 |
| 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. | 33 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Other | 2 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Placebo | Dupilumab | Total |
|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 14 | 41.9 years STANDARD_DEVIATION 17.5 | 39.8 years STANDARD_DEVIATION 16 |
| Lund Mackay (LMK) score | 18.4 score on a scale STANDARD_DEVIATION 3.4 | 17.5 score on a scale STANDARD_DEVIATION 3.8 | 17.9 score on a scale STANDARD_DEVIATION 3.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 12 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 12 Participants | 15 Participants | 27 Participants |
| Sex: Female, Male Female | 4 Participants | 13 Participants | 17 Participants |
| Sex: Female, Male Male | 25 Participants | 20 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 33 |
| other Total, other adverse events | 15 / 28 | 16 / 33 |
| serious Total, serious adverse events | 3 / 28 | 0 / 33 |
Outcome results
Primary
Change From Baseline to Week 52 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score
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.
Time frame: Baseline (Day 1) and Week 52
Population: The intent-to-treat (ITT) population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Dupilumab | Change From Baseline to Week 52 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score | -9.17 score on a scale | Standard Error 0.74 |
Comparison: Each of the imputed complete data were analyzed by fitting an analysis of covariance (ANCOVA) model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: <0.000195% CI: [-9.38, -5.35]ANCOVA
Secondary
Change From Baseline to Week 24 in Endoscopy Nasal Polyp Score (NPS)
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.
Time frame: Baseline (Day 1) and Week 24
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Endoscopy Nasal Polyp Score (NPS) | -0.80 score on a scale | Standard Error 0.38 |
| Dupilumab | Change From Baseline to Week 24 in Endoscopy Nasal Polyp Score (NPS) | -3.16 score on a scale | Standard Error 0.34 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: <0.000195% CI: [-3.31, -1.41]ANCOVA
Secondary
Change From Baseline to Week 24 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary
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.
Time frame: Baseline (Day -7 to Day -1) and Week 24
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Dupilumab | Change From Baseline to Week 24 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary | -1.28 score on a scale | Standard Error 0.15 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: <0.000195% CI: [-1.29, -0.49]ANCOVA
Secondary
Change From Baseline to Week 24 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary
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.
Time frame: Baseline (Day -7 to Day -1) and Week 24
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Dupilumab | Change From Baseline to Week 24 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary | -1.30 score on a scale | Standard Error 0.11 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: <0.000195% CI: [-1.18, -0.56]ANCOVA
Secondary
Change From Baseline to Week 24 in Monthly Average Total Symptom Score (TSS) Derived From the Nasal Symptom Diary
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.
Time frame: Baseline (Day -7 to Day -1) and Week 24
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Dupilumab | Change From Baseline to Week 24 in Monthly Average Total Symptom Score (TSS) Derived From the Nasal Symptom Diary | -3.45 score on a scale | Standard Error 0.31 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: <0.000195% CI: [-3.04, -1.32]ANCOVA
Secondary
Change From Baseline to Week 24 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score
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.
Time frame: Baseline (Day 1) and Week 24
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Dupilumab | Change From Baseline to Week 24 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score | -7.38 score on a scale | Standard Error 0.8 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: <0.000195% CI: [-7.48, -3.43]ANCOVA
Secondary
Change From Baseline to Week 24 in SNOT-22 Total Score
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in SNOT-22 Total Score | -11.63 score on a scale | Standard Error 4.02 |
| Dupilumab | Change From Baseline to Week 24 in SNOT-22 Total Score | -26.74 score on a scale | Standard Error 3.81 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: 0.003295% CI: [-25.15, -5.07]ANCOVA
Secondary
Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT)
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.
Time frame: Baseline (Day 1) and Week 24
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT) | 4.41 score on a scale | Standard Error 1.71 |
| Dupilumab | Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT) | 8.87 score on a scale | Standard Error 1.6 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: 0.039295% CI: [0.22, 8.71]ANCOVA
Secondary
Change From Baseline to Week 52 in 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Dupilumab | Change From Baseline to Week 52 in 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score | -29.94 score on a scale | Standard Error 3.75 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: 0.000495% CI: [-26.86, -7.74]ANCOVA
Secondary
Change From Baseline to Week 52 in Endoscopy NPS
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.
Time frame: Baseline (Day 1) and Week 52
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 52 in Endoscopy NPS | -0.55 score on a scale | Standard Error 0.43 |
| Dupilumab | Change From Baseline to Week 52 in Endoscopy NPS | -3.32 score on a scale | Standard Error 0.39 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: <0.000195% CI: [-3.82, -1.72]ANCOVA
Secondary
Change From Baseline to Week 52 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary
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.
Time frame: Baseline (Day -7 to Day -1) and Week 52
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Dupilumab | Change From Baseline to Week 52 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary | -1.41 score on a scale | Standard Error 0.16 |
Secondary
Change From Baseline to Week 52 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary
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.
Time frame: Baseline (Day -7 to Day -1) and Week 52
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Dupilumab | Change From Baseline to Week 52 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary | -1.57 score on a scale | Standard Error 0.14 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: <0.000195% CI: [-1.77, -1.02]ANCOVA
Secondary
Change From Baseline to Week 52 in Monthly Average TSS Derived From the Nasal Symptom Diary
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.
Time frame: Baseline (Day -7 to Day -1) and Week 52
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Dupilumab | Change From Baseline to Week 52 in Monthly Average TSS Derived From the Nasal Symptom Diary | -4.10 score on a scale | Standard Error 0.35 |
Secondary
Change From Baseline to Week 52 in Three-dimensional CT Total Volume Occupied by Disease in All Sinuses
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.
Time frame: Baseline (Day 1) and Week 52
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Dupilumab | Change From Baseline to Week 52 in Three-dimensional CT Total Volume Occupied by Disease in All Sinuses | -42.04 percent | Standard Error 3.47 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: <0.000195% CI: [-45.59, -27.03]ANCOVA
Secondary
Change From Baseline to Week 52 in UPSIT
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.
Time frame: Baseline (Day 1) and Week 52
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 52 in UPSIT | 2.12 score on a scale | Standard Error 1.73 |
| Dupilumab | Change From Baseline to Week 52 in UPSIT | 9.45 score on a scale | Standard Error 1.57 |
Secondary
Change From Baseline to Weeks 24 and 52 in the Monthly Average Rhinorrhea Score From the Nasal Symptom Diary
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.
Time frame: Baseline (Day -7 to Day -1) and Weeks 24 and 52
Population: The ITT population included all randomized participants.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Dupilumab | Change From Baseline to Weeks 24 and 52 in the Monthly Average Rhinorrhea Score From the Nasal Symptom Diary | Week 24 | -0.92 score on a scale | Standard Error 0.12 |
| Dupilumab | Change From Baseline to Weeks 24 and 52 in the Monthly Average Rhinorrhea Score From the Nasal Symptom Diary | Week 52 | -1.09 score on a scale | Standard Error 0.13 |
Secondary
Change From Baseline to Weeks 24 and 52 in Visual Analog Scale (VAS) Rhinosinusitis
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Dupilumab | Change From Baseline to Weeks 24 and 52 in Visual Analog Scale (VAS) Rhinosinusitis | Week 24 | -4.30 score on a scale | Standard Error 0.58 |
| Dupilumab | Change From Baseline to Weeks 24 and 52 in Visual Analog Scale (VAS) Rhinosinusitis | Week 52 | -5.52 score on a scale | Standard Error 0.54 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 22 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 3 Participants |
| Dupilumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 23 Participants |
| Dupilumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Dupilumab
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.
Time frame: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Dupilumab | 0 Participants |
| Dupilumab | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Dupilumab | 1 Participants |
Secondary
Percentage of Participants Who Received Systemic Corticosteroids (SCS) and/or Underwent or Planned to Undergo Surgery for Allergic Fungal Rhinosinusitis (AFRS) at Week 52
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.
Time frame: Week 52
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 |
| Dupilumab | Percentage of Participants Who Received Systemic Corticosteroids (SCS) and/or Underwent or Planned to Undergo Surgery for Allergic Fungal Rhinosinusitis (AFRS) at Week 52 | 3.0 percentage of particpants |
Comparison: Risk difference was estimated using Mantel-Haenszel estimate and confidence limits, with Mantel-Haenszel stratum weights for time from last surgery (\<=2 years, \>2 years) and region (Americas and Asia) and the Sato variance estimator.p-value: 0.00195% CI: [-46.42, -11.79]Mantel Haenszel
Secondary
Percent Change From Baseline in Fungal-specific IgE at Week 52
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fungal-specific IgE at Week 52 | C. albicans Antigen IgE AB | 15.69 percent change | Standard Deviation 33.17 |
| Placebo | Percent Change From Baseline in Fungal-specific IgE at Week 52 | A. niger Antigen IgE AB | 2.46 percent change | Standard Deviation 55.43 |
| Placebo | Percent Change From Baseline in Fungal-specific IgE at Week 52 | B. spicifera Antigen IgE AB | 19.12 percent change | Standard Deviation 52.1 |
| Placebo | Percent Change From Baseline in Fungal-specific IgE at Week 52 | F. proliferatum Antigen IgE AB | -20.18 percent change | Standard Deviation 38.03 |
| Placebo | Percent Change From Baseline in Fungal-specific IgE at Week 52 | C. lunata Antigen IgE AB | 1.56 percent change | Standard Deviation 29.8 |
| Placebo | Percent Change From Baseline in Fungal-specific IgE at Week 52 | A. flavus Antigen IgE AB | 0.75 percent change | Standard Deviation 44.77 |
| Placebo | 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 |
| Placebo | Percent Change From Baseline in Fungal-specific IgE at Week 52 | S. rostrata Antigen IgE AB | 28.89 percent change | Standard Deviation 52.58 |
| Placebo | Percent Change From Baseline in Fungal-specific IgE at Week 52 | Mould Mix 2 IgE | -17.50 percent change | Standard Deviation 29.93 |
| Placebo | Percent Change From Baseline in Fungal-specific IgE at Week 52 | A. fumigatus Antigen IgE Antibody (AB) | -65.79 percent change | — |
| Dupilumab | Percent Change From Baseline in Fungal-specific IgE at Week 52 | Mould Mix 2 IgE | -66.81 percent change | Standard Deviation 20.86 |
| Dupilumab | Percent Change From Baseline in Fungal-specific IgE at Week 52 | A. fumigatus Antigen IgE Antibody (AB) | -77.20 percent change | Standard Deviation 9 |
| Dupilumab | Percent Change From Baseline in Fungal-specific IgE at Week 52 | C. lunata Antigen IgE AB | -74.82 percent change | Standard Deviation 12.34 |
| Dupilumab | Percent Change From Baseline in Fungal-specific IgE at Week 52 | S. rostrata Antigen IgE AB | -61.77 percent change | Standard Deviation 14.37 |
| Dupilumab | Percent Change From Baseline in Fungal-specific IgE at Week 52 | C. albicans Antigen IgE AB | -63.60 percent change | Standard Deviation 17.06 |
| Dupilumab | Percent Change From Baseline in Fungal-specific IgE at Week 52 | B. spicifera Antigen IgE AB | -56.26 percent change | Standard Deviation 22.36 |
| Dupilumab | Percent Change From Baseline in Fungal-specific IgE at Week 52 | A. niger Antigen IgE AB | -67.48 percent change | Standard Deviation 13.72 |
| Dupilumab | Percent Change From Baseline in Fungal-specific IgE at Week 52 | A. flavus Antigen IgE AB | -52.94 percent change | Standard Deviation 19.62 |
| Dupilumab | Percent Change From Baseline in Fungal-specific IgE at Week 52 | A. tenuis alternata Antigen IgE AB | -56.07 percent change | Standard Deviation 21.78 |
| Dupilumab | Percent Change From Baseline in Fungal-specific IgE at Week 52 | F. proliferatum Antigen IgE AB | -66.09 percent change | Standard Deviation 16.88 |
Secondary
Percent Change From Baseline in Serum Total Immunoglobulin-E (IgE) to Week 52
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Serum Total Immunoglobulin-E (IgE) to Week 52 | 6.91 percent change | Standard Error 10.86 |
| Dupilumab | Percent Change From Baseline in Serum Total Immunoglobulin-E (IgE) to Week 52 | -73.81 percent change | Standard Error 11.4 |
Comparison: Each of the imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, time from last surgery (\<=2 years, \>2 years), and region (Americas and Asia) as covariates.p-value: <0.000195% CI: [-112.82, -48.61]ANCOVA
Secondary
Serum Concentration of Dupilumab Over Time
Blood samples were collected at the specified timepoints to obtain serum concentration of dupilumab.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentration of Dupilumab Over Time | Day 1 | 0.00 nanogram/milliliter | Standard Deviation 0 |
| Placebo | Serum Concentration of Dupilumab Over Time | Week 12 | 47750.00 nanogram/milliliter | Standard Deviation 17828.7 |
| Placebo | Serum Concentration of Dupilumab Over Time | Week 24 | 49597.78 nanogram/milliliter | Standard Deviation 26542.8 |
| Placebo | Serum Concentration of Dupilumab Over Time | Week 52 | 57284.21 nanogram/milliliter | Standard Deviation 27401.32 |