Evaluation of Dupilumab in Patients With Persistent Asthma (Liberty Asthma Quest)

Study Overview
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Brief Summary
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Primary Objective: To evaluate the efficacy of dupilumab (SAR231893 / REGN668) in participants with persistent asthma. Secondary Objectives: To evaluate the safety and tolerability of dupilumab. To evaluate the effect of dupilumab on improving participant-reported outcomes including health-related quality of life. To evaluate dupilumab systemic exposure and incidence of anti-drug antibodies.

Detailed Description
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The total duration of study period for each participant is 67 to 69 weeks, including a screening period of 3 to 5 weeks, treatment period of 52 weeks, and post-treatment follow-up period of 12 weeks.

Official Title
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A Randomized, Double Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Dupilumab
* Drug: Placebo
* Drug: Inhaled corticosteroid (ICS) therapy
* Drug: Albuterol/Salbutamol
* Drug: Levalbuterol/Levosalbutamol


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: -Adults and adolescent participants with a physician diagnosis of asthma for ≥12 months, based on the Global Initiative for Asthma (GINA) 2014 Guidelines and the following criteria: a) Existing treatment with medium to high dose ICS (≥250 mcg of fluticasone propionate twice daily or equipotent ICS daily dosage to a maximum of 2000 mcg/day of fluticasone propionate or equivalent) in combination with a second controller (eg, long-acting beta agonist, leukotriene receptor antagonist) for at least 3 months with a stable dose ≥1 month prior to Visit 1. i) Note for Japan: for participants aged 18 years and older, ICS must be on ≥200 mcg of fluticasone propionate twice daily or equivalent; for participants aged 12 to 17 years, ICS must be ≥100 mcg of fluticasone propionate twice daily or equivalent). ii) Participants requiring a third controller for their asthma will be considered eligible for this study, and it should also be used for at least 3 months with a stable dose ≥1 month prior to Visit 1. Exclusion criteria: Participants <12 years of age or the minimum legal age for adolescents in the country of the investigative site, whichever is higher (For those countries where local regulations permit enrollment of adults only, participant recruitment will be restricted to those who are ≥18 years of age). Weight is less than 30 kilograms. Chronic obstructive pulmonary disease or other lung diseases (eg, idiopathic pulmonary fibrosis, Churg-Strauss Syndrome, etc) which may impair lung function. A participant who experiences a severe asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids at any time from 1 month prior to the Screening Visit up to and including the Baseline Visit). Evidence of lung disease(s) other than asthma, either clinical evidence or imaging (Chest X-ray, CT, MRI) within 12 months of Visit 1 or at the screening visit, as per local standard of care. Note for Japan: According to the request from the health authority, chest X-ray should be performed at screening visit if there is no chest imaging (Chest X-ray, computed tomography [CT], magnetic resonance imaging [MRI]) available within 3 months prior to screening to exclude participants with suspected active or untreated latent tuberculosis. Current smoker or cessation of smoking within 6 months prior to Visit 1. Previous smoker with a smoking history >10 pack-years. Comorbid disease that might interfere with the evaluation of Investigational Medicinal Product. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (for Dupilumab 200 mg) q2w<br>2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection every 2 weeks (q2w) from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. | Drug: Placebo<br>* Solution for injection, Subcutaneous injection in the abdomen, upper thigh or upper arm.<br>Drug: Inhaled corticosteroid (ICS) therapy<br>* Oral inhalation, stable dose (medium or high dose) of ICS in combination with up to 2 other controller medicines (second or third controller therapy)<br>Drug: Albuterol/Salbutamol<br>* Oral inhalation as needed<br>Drug: Levalbuterol/Levosalbutamol<br>* Oral inhalation as needed<br>|
| Experimental: Dupilumab 200 mg q2w<br>2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. | Drug: Dupilumab<br>* Solution for injection, Subcutaneous injection in the abdomen, upper thigh or upper arm.<br>* Other names: REGN668;Drug: Inhaled corticosteroid (ICS) therapy<br>* Oral inhalation, stable dose (medium or high dose) of ICS in combination with up to 2 other controller medicines (second or third controller therapy)<br>Drug: Albuterol/Salbutamol<br>* Oral inhalation as needed<br>Drug: Levalbuterol/Levosalbutamol<br>* Oral inhalation as needed<br>|
| Placebo Comparator: Placebo (for Dupilumab 300 mg) q2w<br>2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. | Drug: Placebo<br>* Solution for injection, Subcutaneous injection in the abdomen, upper thigh or upper arm.<br>Drug: Inhaled corticosteroid (ICS) therapy<br>* Oral inhalation, stable dose (medium or high dose) of ICS in combination with up to 2 other controller medicines (second or third controller therapy)<br>Drug: Albuterol/Salbutamol<br>* Oral inhalation as needed<br>Drug: Levalbuterol/Levosalbutamol<br>* Oral inhalation as needed<br>|
| Experimental: Dupilumab 300 mg q2w<br>2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines . Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. | Drug: Dupilumab<br>* Solution for injection, Subcutaneous injection in the abdomen, upper thigh or upper arm.<br>* Other names: REGN668;Drug: Inhaled corticosteroid (ICS) therapy<br>* Oral inhalation, stable dose (medium or high dose) of ICS in combination with up to 2 other controller medicines (second or third controller therapy)<br>Drug: Albuterol/Salbutamol<br>* Oral inhalation as needed<br>Drug: Levalbuterol/Levosalbutamol<br>* Oral inhalation as needed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: Intent-to-Treat (ITT) Population | A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. | Baseline to Week 52 | 
| Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 12: ITT Population | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Week 12 | 
| Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil >=0.15 Giga/L | A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. | Baseline to Week 52 | 
| Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.15 Giga/L | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Week 12 | 
| Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil >=0.3 Giga/L | A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. | Baseline to Week 52 | 
| Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.3 Giga/L | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Week 12 | 
| Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil <0.3 Giga/L | A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. | Baseline to Week 52 | 
| Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With High Dose ICS at Baseline | A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. | Baseline to Week 52 | 
| Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With High Dose ICS at Baseline | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Week 12 | 
| Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ [S]) Self-Administered Global Score at Week 24: ITT Population | The AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that are most important to participants with asthma. The AQLQ comprises of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item is scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire are averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life. | Baseline, Week 24 | 
| Change From Baseline in AQLQ (S) Self- Administered Global Score at Week 24: ITT Population With Baseline Eosinophil >=0.3 Giga/L | The AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that are most important to participants with asthma. The AQLQ comprises of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item is scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire are averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life. | Baseline, Week 24 | 
| Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 24: ITT Population | The ACQ-5 has 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control. | Baseline, Week 24 | 
| Annualized Rate of Severe Exacerbation Events Resulting in Hospitalization or Emergency Room Visit During The 52-Week Treatment Period: ITT Population | A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations (resulted hospitalization or emergency room visit) that occurred during the treatment period divided by the total number of participant-years treated. | Baseline to Week 52 | 
| Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil <0.3 Giga/L | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Week 12 | 
| Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.3 Giga/L | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Week 12 | 
| Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With High Dose ICS at Baseline | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Week 12 | 
| Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.15 Giga/L | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Week 12 | 
| Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 24, 36, and 52: ITT Population | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Weeks 2, 4, 8, 24, 36, and 52 | 
| Percent Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 24, 36, and 52: ITT Population | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Weeks 2, 4, 8, 24, 36, and 52 | 
| Change From Baseline in Percent Predicted FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52 | 
| Change From Baseline in Morning (AM)/Evening (PM) Peak Expiratory Flow (PEF) at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population | The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at home (morning and evening) while sitting or standing prior to using any medication (if needed) for asthma. | Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52 | 
| Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population | FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. | Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52 | 
| Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population | FEF is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF25-75% is defined as the mean forced expiratory flow between the 25% and 75% of the FVC. | Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52 | 
| Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. | Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52 | 
| Annualized Rate of Loss of Asthma Control (LOAC) Event During The 52-Week Treatment Period: ITT Population | LOAC was defined as any of the following: >=6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in a 24-hour period (compared to baseline) on 2 consecutive days; increase in ICS >=4 times the dose at randomization; use of systemic corticosteroids for >=3 days; hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of LOAC that occurred during the treatment period divided by the total number of participant-years treated. | Baseline to Week 52 | 
| Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During The 52-Week Treatment Period: ITT Population | The time to first severe exacerbation was defined as follows: date of the first event - randomization date +1. For participants who had no event on or before Visit 18 (Week 52) or last contact date, the time was censored at the date of Visit 18 or the last contact date, whichever was earlier. The median time to first severe exacerbation was not estimated; therefore, the probability of severe exacerbation at Weeks 12, 24, 36, and 52, are presented as the descriptive statistics. | Baseline up to Week 52 | 
| Time to First LOAC Event: Kaplan-Meier Estimates During The 52-Week Treatment Period: ITT Population | The time to first LOAC event was defined as follows: date of the first event - first dose date +1. For participants who had no event on or before last dose date + 14 days or last contact date, the time was censored at the last dose date + 14 days or the last contact date, whichever was earlier. | Baseline up to Week 52 | 
| Change From Baseline in ACQ-5 Score at Weeks 2, 4, 8, 12, 36, and 52: ITT Population | The ACQ-5 has 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control. | Baseline, Weeks 2, 4, 8, 12, 36, and 52 | 
| Change From Baseline in Asthma Control Questionnaire 7-item Version (ACQ-7) Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population | The ACQ-7 has 7 questions, the first 5 questions assess the most common asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze plus short-acting bronchodilator use, and FEV1 (pre-bronchodilator % predicted). Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). Clinic staff scored the FEV1% predicted on a 7-point scale. The questions were equally weighted and the ACQ-7 total score was mean of the scores of all 7 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control. | Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52 | 
| Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population | Morning asthma symptom score was determined using AM (ante meridiem) symptom scoring system which evaluated participant's overall asthma symptoms experienced during the night. It ranged from 0 to 4 as: 0= No asthma symptoms, slept through the night, 1= Slept well, but some complaints in the morning, no night time awakenings, 2= Woke up once because of asthma (including early awakening), 3= Woke up several times because of asthma (including early awakening), 4= Bad night, awake most of the night because of asthma. | Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52 | 
| Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population | Evening asthma symptom score was determined using PM (post meridiem) symptom scoring system which evaluated participant's overall asthma symptoms experienced during the day. It ranged from 0 to 4 as: 0=very well, no asthma symptoms, 1=one episode of wheezing, cough, or breathlessness, 2=more than one episode of wheezing, cough, or breathlessness without interference of normal activities, 3=wheezing, cough, or breathlessness most of the day, which interfered to some extent with normal activities, 4=asthma very bad, unable to carry out daily activities as usual. | Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52 | 
| Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population | Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night. | Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52 | 
| Change From Baseline in Number of Puffs of Daily Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population | Participants might administered salbutamol/albuterol or levosalbutamol/levalbuterol as reliever medication as needed during the study. The number of salbutamol/albuterol or levosalbutamol/levalbuterol inhalations were recorded daily by the participants in an electronic diary/peak expiratory flow (PEF) meter. In the case that Nebulizer solutions were used as an alternative delivery method, the nebulizer dose was converted to number of puffs as per following conversion factor: salbutamol/albuterol nebulizer solution (2.5 mg) corresponds to 4 puffs. | Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52 | 
| Change From Baseline in AQLQ (S) Self-Administered Global Score at Weeks 12, 36, and 52: ITT Population | The AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that are most important to participants with asthma. The AQLQ comprises of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item is scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire are averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life. | Baseline, Weeks 12, 36, and 52 | 
| Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Scores at Weeks 12, 24, 36, and 52: ITT Population | EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable). | Baseline, Weeks 12, 24, 36, and 52 | 
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Weeks 12, 24, 36, and 52: ITT Population | The HADS is a general scale to detect states of anxiety and depression already used and validated in asthma, which includes HADS-A and HADS-D subscales. The instrument is comprised of 14 items: 7 related to anxiety (HADS-A) and 7 to depression (HADS-D). Each item on the questionnaire is scored from 0-3. The anxiety/depression score is the sum of the scores of the 7 related items; one can score between 0 and 21 for either anxiety or depression. And the total score is the sum of the scores of the 14 items ranging from 0 (no symptoms) to 42 (severe symptoms), with higher scores indicating higher anxiety/depression complains. | Baseline, Weeks 12, 24, 36, and 52 | 
| Change From Baseline in 22-Item Sino Nasal Outcome Test (SNOT-22) Score at Weeks 12, 24, 36, and 52: ITT Population With Bilateral Nasal Polyposis/Chronic Rhinosinusitis | The SNOT-22 is a validated measure of health related quality of life in sinonasal disease. It is a 22 item questionnaire with each item assigned a score ranging from 0-5. The total score may range from 0 (no disease) -110 (worst disease), lower scores represent better health related quality of life. | Baseline, Weeks 12, 24, 36, and 52 | 
| Change From Baseline in Standardized Rhinoconjunctivitis Quality Of Life Questionnaire, Ages 12+ (RQLQ[S]+12) Score at Weeks 12, 24, 36, and 52: ITT Population With Comorbid Allergic Rhinitis | RQLQ(S)+12 is a self-administered questionnaire with standardized activities developed to measure health-related quality of life signs and symptoms that are most problematic in those 12 to 75 years of age, as a result of perennial or seasonal allergic rhinitis. There are 28 items on RQLQ(S) in 7 domains: activities (3 items), sleep (3 items), non-nose/eye symptoms (7 items), practical problems (3 items), nasal symptoms (4 items), eye symptoms (4 items) and emotional (4 items). RQLQ(S)+12 responses are based on 7-point likert scale with responses ranging from 0 (not troubled) to 6 (extremely troubled). Individual items within RQLQ(S)+12 are equally weighted. The overall score is calculated as the mean score of all items. Higher scores indicated more health-related quality of life impairment (lower scores better). | Baseline, Weeks 12, 24, 36, and 52 |