Asthma
Conditions
Brief summary
Primary Objective: To evaluate the efficacy of different doses and regimens of dupilumab in participants with moderate to severe uncontrolled asthma. Secondary Objective: To evaluate different doses and regimens of dupilumab in participants with moderate to severe uncontrolled asthma, with regard to: * Safety and tolerability * Dupilumab systemic exposure and anti-drug antibodies
Detailed description
Total duration per participant of approximately 43 weeks including a screening period (14-21 days), a randomized treatment period (24 weeks), and a post-treatment period (16 weeks).
Interventions
DRUGDupilumab
Solution for injection, Subcutaneous injection
DRUGplacebo
Solution for injection, Subcutaneous injection
DRUGICS/LABA therapy
Oral inhalation, Prior therapy with Mometasone furoate /formoterol, budesonide / formoterol, or fluticasone propionate / salmeterol continued at stable dose
Oral inhalation as needed
DRUGLevosalbutamol/levalbuterol
Oral inhalation as needed
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants with a physician diagnosis of moderate to severe, uncontrolled asthma for \>=12 months, based on the Global Initiative for Asthma (GINA) 2009 Guidelines and: * Existing treatment with moderate or high-dose inhaled corticosteroid / long-acting beta-2 agonist * Forced expiratory volume (FEV1) 40 to 80% of predicted normal * Asthma Control Questionnaire, 5-question version (ACQ-5) score \>=1.5 * Reversibility of at least 12% and 200 mL in forced expiratory volume (FEV1) * Had experienced, within prior year: hospitalization, emergency or urgent care visit or systemic corticosteroid treatment for worsening asthma
Exclusion criteria
* Participants \<18 years * Chronic obstructive pulmonary disease (COPD) or other lung diseases (eg, emphysema, idiopathic pulmonary fibrosis, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis) which impaired pulmonary function tests * Chest X-ray within 12 months of screening visit or at screening visit with clinically significant findings of lung disease(s) other than asthma * Current smoker or cessation of smoking within 6 months prior to Visit 1 * Previous smoker with a smoking history \>10 pack-years The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Baseline, Week 12 | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. |
| Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Baseline, Week 12 | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population | Baseline to Week 24 | 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. |
| Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population | Baseline to Week 24 | 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. |
| Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Baseline up to Week 24 | The time to first severe exacerbation was defined as the time from the date of first dose to the date of the first severe exacerbation event. For participants who had no severe exacerbation on or before last dose date + 14 days, it was censored at the date of last dose date + 14 days. The median time to first severe exacerbation was not estimated because the number of severe exacerbations was too low in the Dupilumab arms. Therefore, alternative Kaplan-Meier statistics, the probability of severe exacerbation at Week 12 and 24, are presented as the descriptive measure statistics. |
| Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Baseline up to Week 24 | The time to first severe exacerbation was defined as the time from the date of first dose to the date of the first severe exacerbation event. For participants who had no severe exacerbation on or before last dose date + 14 days, it was censored at the date of last dose date + 14 days. The median time to first severe exacerbation was not estimated because the number of severe exacerbations was too low in the Dupilumab arms. Therefore, alternative Kaplan-Meier statistics, the probability of severe exacerbation at Week 12 and 24, are presented as the descriptive measure statistics. |
| Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population | Baseline to Week 24 | 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 inhaled corticosteroid (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. |
| Annualized Event Rate of LOAC During The Treatment Period: ITT Population | Baseline to Week 24 | 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. |
| Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Baseline up to Week 24 | The time to first LOAC event was defined as the time from the date of first dose to the date of the first LOAC event. For participants who had no LOAC event on or before last dose date + 14 days, it was censored at the date of last dose date + 14 days. The median time to first LOAC was not estimated because the number of LOAC was too low in the Dupilumab arms. Therefore, alternative Kaplan-Meier statistics, the probability of LOAC at Week 12 and 24, are presented as the descriptive measure statistics. |
| Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Baseline up to Week 24 | The time to first LOAC event was defined as the time from the date of first dose to the date of the first LOAC event. For participants who had no LOAC event on or before last dose date + 14 days, it was censored at the date of last dose date + 14 days. The median time to first LOAC was not estimated because the number of LOAC was too low in the Dupilumab arms. Therefore, alternative Kaplan-Meier statistics, the probability of LOAC at Week 12 and 24, are presented as the descriptive measure statistics. |
| Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline, Week 12 | 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. |
| Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population | Baseline, Week 12 | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. |
| Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline, Week 12 | 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. |
| Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Baseline, Week 12 | Evening asthma symptom score was determined using PM 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. |
| Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Baseline, Week 12 | 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. |
| Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Baseline, Week 12 | 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. |
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Baseline, Week 12 | 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. |
| Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Baseline, Week 12 | 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. |
| Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Baseline, Week 12 | 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 by the participants in their electronic diary. |
| Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Baseline, Week 12 | 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 by the participants in their electronic diary. |
| Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Baseline, Week 12 | Morning asthma symptom score was determined using AM 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. |
| Percent Change From Baseline in FEV1 at Week 12: ITT Population | Baseline, Week 12 | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. |
Countries
Argentina, Australia, Chile, France, Italy, Japan, Mexico, New Zealand, Poland, Russia, South Africa, South Korea, Spain, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
The study was conducted at 201 sites in 16 countries. A total of 1532 participants were screened between June 2013 and June 2014, of which, 776 participants were randomized at 174 sites in 15 countries. 756 participants were screen failures mainly due to exclusion criteria met and inclusion criteria not met.
Pre-assignment details
Randomization was stratified using blood eosinophils count (eosinophils \>=0.3 Giga/L \[G/L\]; eosinophils 0.2 to 0.299 G/L; eosinophils\<0.2 G/L) and country. Assignment was done by Interactive Voice/Web Response System (1:1:1:1:1) for Placebo and Dupilumab (300 mg every 2 weeks \[q2w\]; 200 mg q2w; 300 mg every 4 week \[q4w\] and 200 mg q4w).
Participants by arm
| Arm | Count |
|---|---|
| Placebo q2w 2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 (Week 1) followed by a single injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | 158 |
| Dupilumab 300 mg q2w 2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1), followed by a single 300 mg injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | 157 |
| Dupilumab 200 mg q2w 2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1), followed by a single 200 mg injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | 150 |
| Dupilumab 300 mg q4w 2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | 157 |
| Dupilumab 200 mg q4w 2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | 154 |
| Total | 776 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 | 6 | 10 | 7 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other than specified above | 3 | 3 | 3 | 5 | 8 |
| Overall Study | Poor compliance to protocol | 3 | 0 | 2 | 0 | 0 |
| Overall Study | Randomized but not treated | 0 | 1 | 2 | 0 | 4 |
Baseline characteristics
| Characteristic | Dupilumab 300 mg q2w | Dupilumab 200 mg q2w | Placebo q2w | Dupilumab 300 mg q4w | Dupilumab 200 mg q4w | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 12.4 | 51 years STANDARD_DEVIATION 13.4 | 49 years STANDARD_DEVIATION 12.7 | 47.9 years STANDARD_DEVIATION 13.1 | 47.9 years STANDARD_DEVIATION 13.1 | 48.6 years STANDARD_DEVIATION 13 |
| Number of Participants According to Blood Eosinophil Count <0.3 G/L | 93 Participants | 85 Participants | 90 Participants | 91 Participants | 92 Participants | 451 Participants |
| Number of Participants According to Blood Eosinophil Count >=0.3 G/L | 64 Participants | 65 Participants | 68 Participants | 66 Participants | 62 Participants | 325 Participants |
| Race/Ethnicity, Customized Hispanic Or Latino | 29 Participants | 29 Participants | 31 Participants | 33 Participants | 26 Participants | 148 Participants |
| Race/Ethnicity, Customized Not Hispanic Or Latino | 128 Participants | 121 Participants | 127 Participants | 124 Participants | 128 Participants | 628 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 25 Participants | 25 Participants | 23 Participants | 20 Participants | 115 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 9 Participants | 12 Participants | 7 Participants | 42 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 5 Participants | 1 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) White | 129 Participants | 114 Participants | 119 Participants | 120 Participants | 125 Participants | 607 Participants |
| Sex: Female, Male Female | 103 Participants | 96 Participants | 104 Participants | 100 Participants | 87 Participants | 490 Participants |
| Sex: Female, Male Male | 54 Participants | 54 Participants | 54 Participants | 57 Participants | 67 Participants | 286 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 158 | 0 / 156 | 0 / 148 | 2 / 157 | 0 / 150 |
| other Total, other adverse events | 88 / 158 | 95 / 156 | 81 / 148 | 96 / 157 | 74 / 150 |
| serious Total, serious adverse events | 9 / 158 | 13 / 156 | 10 / 148 | 16 / 157 | 6 / 150 |
Outcome results
Primary
Absolute Change From Baseline in 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.
Time frame: Baseline, Week 12
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Week 12 | 2.01 liter | Standard Deviation 0.69 |
| Placebo q2w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Change from baseline at Week 12 | 0.13 liter | Standard Deviation 0.37 |
| Placebo q2w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Baseline | 1.82 liter | Standard Deviation 0.55 |
| Dupilumab 300 mg q2w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Change from baseline at Week 12 | 0.26 liter | Standard Deviation 0.39 |
| Dupilumab 300 mg q2w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Week 12 | 2.12 liter | Standard Deviation 0.59 |
| Dupilumab 300 mg q2w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Baseline | 1.85 liter | Standard Deviation 0.53 |
| Dupilumab 200 mg q2w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Baseline | 1.79 liter | Standard Deviation 0.52 |
| Dupilumab 200 mg q2w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Change from baseline at Week 12 | 0.32 liter | Standard Deviation 0.38 |
| Dupilumab 200 mg q2w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Week 12 | 2.12 liter | Standard Deviation 0.68 |
| Dupilumab 300 mg q4w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Baseline | 1.86 liter | Standard Deviation 0.57 |
| Dupilumab 300 mg q4w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Change from baseline at Week 12 | 0.24 liter | Standard Deviation 0.4 |
| Dupilumab 300 mg q4w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Week 12 | 2.14 liter | Standard Deviation 0.69 |
| Dupilumab 200 mg q4w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Change from baseline at Week 12 | 0.20 liter | Standard Deviation 0.41 |
| Dupilumab 200 mg q4w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Week 12 | 2.07 liter | Standard Deviation 0.63 |
| Dupilumab 200 mg q4w | Absolute Change From Baseline in FEV1 at Week 12: ITT Population | Baseline | 1.88 liter | Standard Deviation 0.54 |
Comparison: Analysis was performed using MMRM approach including available FEV1 data from baseline to Week 12 and treatment group as a factor. A step-down procedure was used to strongly control the overall type I error rate for testing multiple doses against placebo. The hierarchy was 300 mg q2w, 200 mg q2w, 300 mg q4w and 200 mg q4w.p-value: 0.000295% CI: [0.08, 0.25]Mixed Models Analysis
p-value: <0.000195% CI: [0.011, 0.28]Mixed Models Analysis
p-value: 0.004895% CI: [0.04, 0.21]Mixed Models Analysis
p-value: 0.030495% CI: [0.01, 0.18]Mixed Models Analysis
Primary
Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population
FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time frame: Baseline, Week 12
Population: HEos-ITT population: subset of intent to treat (ITT) population (defined as randomized population analyzed according to the treatment group allocated by randomization, regardless of whether the treatment was actually received) which included participants with baseline blood eosinophils \>=0.3 G/L.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Baseline | 1.86 liter | Standard Deviation 0.68 |
| Placebo q2w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Change from baseline at Week 12 | 0.18 liter | Standard Deviation 0.38 |
| Placebo q2w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Week 12 | 2.13 liter | Standard Deviation 0.78 |
| Dupilumab 300 mg q2w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Week 12 | 2.12 liter | Standard Deviation 0.54 |
| Dupilumab 300 mg q2w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Baseline | 1.77 liter | Standard Deviation 0.5 |
| Dupilumab 300 mg q2w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Change from baseline at Week 12 | 0.36 liter | Standard Deviation 0.46 |
| Dupilumab 200 mg q2w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Week 12 | 2.26 liter | Standard Deviation 0.68 |
| Dupilumab 200 mg q2w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Baseline | 1.8 liter | Standard Deviation 0.52 |
| Dupilumab 200 mg q2w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Change from baseline at Week 12 | 0.45 liter | Standard Deviation 0.4 |
| Dupilumab 300 mg q4w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Baseline | 1.87 liter | Standard Deviation 0.6 |
| Dupilumab 300 mg q4w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Change from baseline at Week 12 | 0.35 liter | Standard Deviation 0.43 |
| Dupilumab 300 mg q4w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Week 12 | 2.26 liter | Standard Deviation 0.7 |
| Dupilumab 200 mg q4w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Week 12 | 2.09 liter | Standard Deviation 0.54 |
| Dupilumab 200 mg q4w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Baseline | 1.8 liter | Standard Deviation 0.49 |
| Dupilumab 200 mg q4w | Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population | Change from baseline at Week 12 | 0.26 liter | Standard Deviation 0.47 |
Comparison: Analysis was performed using mixed effect model with repeated measures (MMRM) approach including available FEV1 data from baseline to Week 12 and treatment group as a factor. A step-down procedure was used to strongly control the overall type I error rate for testing multiple doses against placebo. The hierarchy was 300 mg q2w, 200 mg q2w, 300 mg q4w, and 200 mg q4w.p-value: 0.006395% CI: [0.06, 0.36]Mixed Models Analysis
p-value: 0.000895% CI: [0.11, 0.4]Mixed Models Analysis
p-value: 0.021295% CI: [0.03, 0.32]Mixed Models Analysis
p-value: 0.277495% CI: [-0.07, 0.23]Mixed Models Analysis
Secondary
Annualized Event Rate of LOAC During The 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.
Time frame: Baseline to Week 24
Population: ITT population. Here 'overall number of participants analyzed' signifies participants of the ITT population who were treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo q2w | Annualized Event Rate of LOAC During The Treatment Period: ITT Population | 1.107 LOAC per participant-year |
| Dupilumab 300 mg q2w | Annualized Event Rate of LOAC During The Treatment Period: ITT Population | 0.326 LOAC per participant-year |
| Dupilumab 200 mg q2w | Annualized Event Rate of LOAC During The Treatment Period: ITT Population | 0.347 LOAC per participant-year |
| Dupilumab 300 mg q4w | Annualized Event Rate of LOAC During The Treatment Period: ITT Population | 0.73 LOAC per participant-year |
| Dupilumab 200 mg q4w | Annualized Event Rate of LOAC During The Treatment Period: ITT Population | 0.563 LOAC per participant-year |
Secondary
Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-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 inhaled corticosteroid (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.
Time frame: Baseline to Week 24
Population: HEos-ITT population. Here 'overall number of participants analyzed' signifies participants of the HEos-ITT population who were treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo q2w | Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population | 1.312 LOAC per participant-year |
| Dupilumab 300 mg q2w | Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population | 0.322 LOAC per participant-year |
| Dupilumab 200 mg q2w | Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population | 0.446 LOAC per participant-year |
| Dupilumab 300 mg q4w | Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population | 0.788 LOAC per participant-year |
| Dupilumab 200 mg q4w | Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population | 0.424 LOAC per participant-year |
Secondary
Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-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.
Time frame: Baseline to Week 24
Population: HEos-ITT population. Here 'overall number of participants analyzed' signifies participants of the HEos-ITT population who were treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo q2w | Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population | 1.044 exacerbation per participant-year |
| Dupilumab 300 mg q2w | Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population | 0.201 exacerbation per participant-year |
| Dupilumab 200 mg q2w | Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population | 0.30 exacerbation per participant-year |
| Dupilumab 300 mg q4w | Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population | 0.678 exacerbation per participant-year |
| Dupilumab 200 mg q4w | Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population | 0.358 exacerbation per participant-year |
Secondary
Annualized Event Rate of Severe Exacerbation During The 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 that occurred during the treatment period divided by the total number of participant-years treated.
Time frame: Baseline to Week 24
Population: ITT population. Here 'overall number of participants analyzed' signifies participants of the ITT population who were treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo q2w | Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population | 0.897 exacerbation per participant-year |
| Dupilumab 300 mg q2w | Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population | 0.265 exacerbation per participant-year |
| Dupilumab 200 mg q2w | Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population | 0.269 exacerbation per participant-year |
| Dupilumab 300 mg q4w | Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population | 0.599 exacerbation per participant-year |
| Dupilumab 200 mg q4w | Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population | 0.415 exacerbation per participant-year |
Secondary
Change From Baseline in ACQ-5 Score at Week 12: 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.
Time frame: Baseline, Week 12
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Week 12 | 1.55 scores on a scale | Standard Deviation 1 |
| Placebo q2w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Baseline | 2.69 scores on a scale | Standard Deviation 0.8 |
| Placebo q2w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Change from baseline at Week 12 | -1.11 scores on a scale | Standard Deviation 0.93 |
| Dupilumab 300 mg q2w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Week 12 | 1.41 scores on a scale | Standard Deviation 1.02 |
| Dupilumab 300 mg q2w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Change from baseline at Week 12 | -1.38 scores on a scale | Standard Deviation 1.1 |
| Dupilumab 300 mg q2w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Baseline | 2.80 scores on a scale | Standard Deviation 0.83 |
| Dupilumab 200 mg q2w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Change from baseline at Week 12 | -1.35 scores on a scale | Standard Deviation 1.05 |
| Dupilumab 200 mg q2w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Week 12 | 1.38 scores on a scale | Standard Deviation 0.96 |
| Dupilumab 200 mg q2w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Baseline | 2.73 scores on a scale | Standard Deviation 0.82 |
| Dupilumab 300 mg q4w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Week 12 | 1.38 scores on a scale | Standard Deviation 0.86 |
| Dupilumab 300 mg q4w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Change from baseline at Week 12 | -1.32 scores on a scale | Standard Deviation 1.02 |
| Dupilumab 300 mg q4w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Baseline | 2.70 scores on a scale | Standard Deviation 0.79 |
| Dupilumab 200 mg q4w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Change from baseline at Week 12 | -1.24 scores on a scale | Standard Deviation 0.95 |
| Dupilumab 200 mg q4w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Baseline | 2.78 scores on a scale | Standard Deviation 0.84 |
| Dupilumab 200 mg q4w | Change From Baseline in ACQ-5 Score at Week 12: ITT Population | Week 12 | 1.49 scores on a scale | Standard Deviation 0.98 |
Secondary
Change From Baseline in AQLQ Global Score at Week 12: 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.
Time frame: Baseline, Week 12
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Baseline | 4.12 scores on a scale | Standard Deviation 1.1 |
| Placebo q2w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Change from baseline at Week 12 | 0.86 scores on a scale | Standard Deviation 0.99 |
| Placebo q2w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Week 12 | 5.00 scores on a scale | Standard Deviation 1.1 |
| Dupilumab 300 mg q2w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Week 12 | 5.13 scores on a scale | Standard Deviation 1.22 |
| Dupilumab 300 mg q2w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Baseline | 3.91 scores on a scale | Standard Deviation 1.13 |
| Dupilumab 300 mg q2w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Change from baseline at Week 12 | 1.25 scores on a scale | Standard Deviation 1.1 |
| Dupilumab 200 mg q2w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Week 12 | 5.22 scores on a scale | Standard Deviation 1.11 |
| Dupilumab 200 mg q2w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Baseline | 4.03 scores on a scale | Standard Deviation 1.15 |
| Dupilumab 200 mg q2w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Change from baseline at Week 12 | 1.19 scores on a scale | Standard Deviation 1.05 |
| Dupilumab 300 mg q4w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Baseline | 4.02 scores on a scale | Standard Deviation 1.01 |
| Dupilumab 300 mg q4w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Change from baseline at Week 12 | 1.03 scores on a scale | Standard Deviation 1.02 |
| Dupilumab 300 mg q4w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Week 12 | 5.04 scores on a scale | Standard Deviation 1.13 |
| Dupilumab 200 mg q4w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Week 12 | 5.03 scores on a scale | Standard Deviation 1.12 |
| Dupilumab 200 mg q4w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Baseline | 4.00 scores on a scale | Standard Deviation 1.09 |
| Dupilumab 200 mg q4w | Change From Baseline in AQLQ Global Score at Week 12: ITT Population | Change from baseline at Week 12 | 0.98 scores on a scale | Standard Deviation 1.02 |
Secondary
Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-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.
Time frame: Baseline, Week 12
Population: HEos-ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Week 12 | 1.52 scores on a scale | Standard Deviation 1.09 |
| Placebo q2w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Baseline | 2.55 scores on a scale | Standard Deviation 0.84 |
| Placebo q2w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -1.03 scores on a scale | Standard Deviation 0.93 |
| Dupilumab 300 mg q2w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -1.72 scores on a scale | Standard Deviation 1.14 |
| Dupilumab 300 mg q2w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Week 12 | 1.20 scores on a scale | Standard Deviation 0.96 |
| Dupilumab 300 mg q2w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Baseline | 2.98 scores on a scale | Standard Deviation 0.9 |
| Dupilumab 200 mg q2w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Baseline | 2.65 scores on a scale | Standard Deviation 0.74 |
| Dupilumab 200 mg q2w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Week 12 | 1.20 scores on a scale | Standard Deviation 0.88 |
| Dupilumab 200 mg q2w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -1.40 scores on a scale | Standard Deviation 1.03 |
| Dupilumab 300 mg q4w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Baseline | 2.69 scores on a scale | Standard Deviation 0.81 |
| Dupilumab 300 mg q4w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -1.39 scores on a scale | Standard Deviation 1.02 |
| Dupilumab 300 mg q4w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Week 12 | 1.27 scores on a scale | Standard Deviation 0.91 |
| Dupilumab 200 mg q4w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Baseline | 2.76 scores on a scale | Standard Deviation 0.91 |
| Dupilumab 200 mg q4w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -1.38 scores on a scale | Standard Deviation 0.9 |
| Dupilumab 200 mg q4w | Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population | Week 12 | 1.39 scores on a scale | Standard Deviation 0.94 |
Secondary
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-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.
Time frame: Baseline, Week 12
Population: HEos-ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | 0.80 scores on a scale | Standard Deviation 1.02 |
| Placebo q2w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Week 12 | 5.05 scores on a scale | Standard Deviation 1.22 |
| Placebo q2w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Baseline | 4.16 scores on a scale | Standard Deviation 1.27 |
| Dupilumab 300 mg q2w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Week 12 | 5.35 scores on a scale | Standard Deviation 1.21 |
| Dupilumab 300 mg q2w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | 1.54 scores on a scale | Standard Deviation 1.18 |
| Dupilumab 300 mg q2w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Baseline | 3.82 scores on a scale | Standard Deviation 1.13 |
| Dupilumab 200 mg q2w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Baseline | 4.02 scores on a scale | Standard Deviation 1.15 |
| Dupilumab 200 mg q2w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | 1.42 scores on a scale | Standard Deviation 0.97 |
| Dupilumab 200 mg q2w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Week 12 | 5.41 scores on a scale | Standard Deviation 1.06 |
| Dupilumab 300 mg q4w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Week 12 | 5.06 scores on a scale | Standard Deviation 1.19 |
| Dupilumab 300 mg q4w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Baseline | 3.99 scores on a scale | Standard Deviation 1.06 |
| Dupilumab 300 mg q4w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | 1.08 scores on a scale | Standard Deviation 0.97 |
| Dupilumab 200 mg q4w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | 1.16 scores on a scale | Standard Deviation 1.01 |
| Dupilumab 200 mg q4w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Baseline | 3.89 scores on a scale | Standard Deviation 1.88 |
| Dupilumab 200 mg q4w | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population | Week 12 | 5.05 scores on a scale | Standard Deviation 1.29 |
Secondary
Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-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.
Time frame: Baseline, Week 12
Population: HEos ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Week 12 | 0.95 scores on a scale | Standard Deviation 0.71 |
| Placebo q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.35 scores on a scale | Standard Deviation 0.71 |
| Placebo q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline | 1.33 scores on a scale | Standard Deviation 0.83 |
| Dupilumab 300 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline | 1.72 scores on a scale | Standard Deviation 0.89 |
| Dupilumab 300 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Week 12 | 0.88 scores on a scale | Standard Deviation 0.91 |
| Dupilumab 300 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.84 scores on a scale | Standard Deviation 0.87 |
| Dupilumab 200 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.62 scores on a scale | Standard Deviation 0.7 |
| Dupilumab 200 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Week 12 | 0.89 scores on a scale | Standard Deviation 0.79 |
| Dupilumab 200 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline | 1.46 scores on a scale | Standard Deviation 0.73 |
| Dupilumab 300 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Week 12 | 0.76 scores on a scale | Standard Deviation 0.84 |
| Dupilumab 300 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.73 scores on a scale | Standard Deviation 0.77 |
| Dupilumab 300 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline | 1.52 scores on a scale | Standard Deviation 0.72 |
| Dupilumab 200 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline | 1.39 scores on a scale | Standard Deviation 0.87 |
| Dupilumab 200 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.69 scores on a scale | Standard Deviation 0.7 |
| Dupilumab 200 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population | Week 12 | 0.69 scores on a scale | Standard Deviation 0.68 |
Secondary
Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population
Evening asthma symptom score was determined using PM 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.
Time frame: Baseline, Week 12
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Baseline | 1.32 scores on a scale | Standard Deviation 0.81 |
| Placebo q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Week 12 | 1.02 scores on a scale | Standard Deviation 0.73 |
| Placebo q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Change from baseline at Week 12 | -0.27 scores on a scale | Standard Deviation 0.76 |
| Dupilumab 300 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Week 12 | 0.95 scores on a scale | Standard Deviation 0.88 |
| Dupilumab 300 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Change from baseline at Week 12 | -0.52 scores on a scale | Standard Deviation 0.79 |
| Dupilumab 300 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Baseline | 1.47 scores on a scale | Standard Deviation 0.85 |
| Dupilumab 200 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Week 12 | 0.95 scores on a scale | Standard Deviation 0.81 |
| Dupilumab 200 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Baseline | 1.42 scores on a scale | Standard Deviation 0.79 |
| Dupilumab 200 mg q2w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Change from baseline at Week 12 | -0.52 scores on a scale | Standard Deviation 0.8 |
| Dupilumab 300 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Baseline | 1.50 scores on a scale | Standard Deviation 0.74 |
| Dupilumab 300 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Change from baseline at Week 12 | -0.59 scores on a scale | Standard Deviation 0.79 |
| Dupilumab 300 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Week 12 | 0.89 scores on a scale | Standard Deviation 0.79 |
| Dupilumab 200 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Week 12 | 0.89 scores on a scale | Standard Deviation 0.81 |
| Dupilumab 200 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Baseline | 1.47 scores on a scale | Standard Deviation 0.84 |
| Dupilumab 200 mg q4w | Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population | Change from baseline at Week 12 | -0.54 scores on a scale | Standard Deviation 0.71 |
Secondary
Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-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.
Time frame: Baseline, Week 12
Population: HEos-ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline | 1.15 scores on a scale | Standard Deviation 0.82 |
| Placebo q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Week 12 | 0.83 scores on a scale | Standard Deviation 0.66 |
| Placebo q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.29 scores on a scale | Standard Deviation 0.7 |
| Dupilumab 300 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Week 12 | 0.78 scores on a scale | Standard Deviation 0.88 |
| Dupilumab 300 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline | 1.45 scores on a scale | Standard Deviation 0.81 |
| Dupilumab 300 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.66 scores on a scale | Standard Deviation 0.67 |
| Dupilumab 200 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Week 12 | 0.70 scores on a scale | Standard Deviation 0.69 |
| Dupilumab 200 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.55 scores on a scale | Standard Deviation 0.75 |
| Dupilumab 200 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline | 1.22 scores on a scale | Standard Deviation 0.81 |
| Dupilumab 300 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.57 scores on a scale | Standard Deviation 0.63 |
| Dupilumab 300 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Week 12 | 0.70 scores on a scale | Standard Deviation 0.78 |
| Dupilumab 300 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline | 1.31 scores on a scale | Standard Deviation 0.72 |
| Dupilumab 200 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Baseline | 1.18 scores on a scale | Standard Deviation 0.82 |
| Dupilumab 200 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Week 12 | 0.63 scores on a scale | Standard Deviation 0.62 |
| Dupilumab 200 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.57 scores on a scale | Standard Deviation 0.6 |
Secondary
Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population
Morning asthma symptom score was determined using AM 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.
Time frame: Baseline, Week 12
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Baseline | 1.17 scores on a scale | Standard Deviation 0.79 |
| Placebo q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Change from baseline at Week 12 | -0.23 scores on a scale | Standard Deviation 0.7 |
| Placebo q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Week 12 | 0.90 scores on a scale | Standard Deviation 0.67 |
| Dupilumab 300 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Week 12 | 0.82 scores on a scale | Standard Deviation 0.79 |
| Dupilumab 300 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Baseline | 1.25 scores on a scale | Standard Deviation 0.78 |
| Dupilumab 300 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Change from baseline at Week 12 | -0.43 scores on a scale | Standard Deviation 0.7 |
| Dupilumab 200 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Week 12 | 0.79 scores on a scale | Standard Deviation 0.77 |
| Dupilumab 200 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Baseline | 1.24 scores on a scale | Standard Deviation 0.81 |
| Dupilumab 200 mg q2w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Change from baseline at Week 12 | -0.46 scores on a scale | Standard Deviation 0.75 |
| Dupilumab 300 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Baseline | 1.33 scores on a scale | Standard Deviation 0.78 |
| Dupilumab 300 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Change from baseline at Week 12 | -0.52 scores on a scale | Standard Deviation 0.65 |
| Dupilumab 300 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Week 12 | 0.80 scores on a scale | Standard Deviation 0.73 |
| Dupilumab 200 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Week 12 | 0.72 scores on a scale | Standard Deviation 0.68 |
| Dupilumab 200 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Baseline | 1.29 scores on a scale | Standard Deviation 0.82 |
| Dupilumab 200 mg q4w | Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population | Change from baseline at Week 12 | -0.54 scores on a scale | Standard Deviation 0.64 |
Secondary
Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-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 by the participants in their electronic diary.
Time frame: Baseline, Week 12
Population: HEos-ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Week 12 | 1.88 inhalations per day | Standard Deviation 2.53 |
| Placebo q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Baseline | 2.53 inhalations per day | Standard Deviation 2.77 |
| Placebo q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.51 inhalations per day | Standard Deviation 1.74 |
| Dupilumab 300 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -1.47 inhalations per day | Standard Deviation 2.31 |
| Dupilumab 300 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Baseline | 3.61 inhalations per day | Standard Deviation 3.56 |
| Dupilumab 300 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Week 12 | 2.14 inhalations per day | Standard Deviation 3.22 |
| Dupilumab 200 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Baseline | 3.02 inhalations per day | Standard Deviation 2.85 |
| Dupilumab 200 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -0.93 inhalations per day | Standard Deviation 2.31 |
| Dupilumab 200 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Week 12 | 2.15 inhalations per day | Standard Deviation 2.67 |
| Dupilumab 300 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Baseline | 3.15 inhalations per day | Standard Deviation 2.7 |
| Dupilumab 300 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Week 12 | 1.85 inhalations per day | Standard Deviation 2.75 |
| Dupilumab 300 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -1.49 inhalations per day | Standard Deviation 2.37 |
| Dupilumab 200 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Baseline | 2.42 inhalations per day | Standard Deviation 2.75 |
| Dupilumab 200 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Change from baseline at Week 12 | -1.01 inhalations per day | Standard Deviation 2 |
| Dupilumab 200 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population | Week 12 | 1.36 inhalations per day | Standard Deviation 1.76 |
Secondary
Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: 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 by the participants in their electronic diary.
Time frame: Baseline, Week 12
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Baseline | 2.72 inhalations per day | Standard Deviation 2.73 |
| Placebo q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Change from baseline at Week 12 | -0.44 inhalations per day | Standard Deviation 1.75 |
| Placebo q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Week 12 | 2.20 inhalations per day | Standard Deviation 2.57 |
| Dupilumab 300 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Week 12 | 2.30 inhalations per day | Standard Deviation 3.02 |
| Dupilumab 300 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Baseline | 3.25 inhalations per day | Standard Deviation 3.15 |
| Dupilumab 300 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Change from baseline at Week 12 | -0.95 inhalations per day | Standard Deviation 2.05 |
| Dupilumab 200 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Week 12 | 2.03 inhalations per day | Standard Deviation 2.46 |
| Dupilumab 200 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Baseline | 2.98 inhalations per day | Standard Deviation 2.74 |
| Dupilumab 200 mg q2w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Change from baseline at Week 12 | -0.99 inhalations per day | Standard Deviation 2.27 |
| Dupilumab 300 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Baseline | 3.36 inhalations per day | Standard Deviation 3.43 |
| Dupilumab 300 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Change from baseline at Week 12 | -1.35 inhalations per day | Standard Deviation 2.84 |
| Dupilumab 300 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Week 12 | 2.09 inhalations per day | Standard Deviation 2.73 |
| Dupilumab 200 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Week 12 | 1.99 inhalations per day | Standard Deviation 2.42 |
| Dupilumab 200 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Baseline | 3.01 inhalations per day | Standard Deviation 2.87 |
| Dupilumab 200 mg q4w | Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population | Change from baseline at Week 12 | -0.92 inhalations per day | Standard Deviation 2.16 |
Secondary
Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population
FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time frame: Baseline, Week 12
Population: HEos-ITT population. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population | 10.07 percent change | Standard Deviation 19.65 |
| Dupilumab 300 mg q2w | Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population | 25.29 percent change | Standard Deviation 36.15 |
| Dupilumab 200 mg q2w | Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population | 27.42 percent change | Standard Deviation 25.68 |
| Dupilumab 300 mg q4w | Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population | 20.68 percent change | Standard Deviation 24.86 |
| Dupilumab 200 mg q4w | Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population | 18.07 percent change | Standard Deviation 29.18 |
Secondary
Percent Change From Baseline in 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.
Time frame: Baseline, Week 12
Population: ITT population. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Percent Change From Baseline in FEV1 at Week 12: ITT Population | 7.04 percent change | Standard Deviation 19.26 |
| Dupilumab 300 mg q2w | Percent Change From Baseline in FEV1 at Week 12: ITT Population | 16.64 percent change | Standard Deviation 27.78 |
| Dupilumab 200 mg q2w | Percent Change From Baseline in FEV1 at Week 12: ITT Population | 19.15 percent change | Standard Deviation 23.53 |
| Dupilumab 300 mg q4w | Percent Change From Baseline in FEV1 at Week 12: ITT Population | 13.55 percent change | Standard Deviation 23.01 |
| Dupilumab 200 mg q4w | Percent Change From Baseline in FEV1 at Week 12: ITT Population | 13.04 percent change | Standard Deviation 24.21 |
Secondary
Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population
The time to first LOAC event was defined as the time from the date of first dose to the date of the first LOAC event. For participants who had no LOAC event on or before last dose date + 14 days, it was censored at the date of last dose date + 14 days. The median time to first LOAC was not estimated because the number of LOAC was too low in the Dupilumab arms. Therefore, alternative Kaplan-Meier statistics, the probability of LOAC at Week 12 and 24, are presented as the descriptive measure statistics.
Time frame: Baseline up to Week 24
Population: HEos-ITT population. Here 'overall number of participants analyzed' signifies participants of the HEos-ITT population who were treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Probability at Week 12 | 0.30 probability of LOAC |
| Placebo q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Probability at Week 24 | 0.392 probability of LOAC |
| Dupilumab 300 mg q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Probability at Week 24 | 0.166 probability of LOAC |
| Dupilumab 300 mg q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Probability at Week 12 | 0.115 probability of LOAC |
| Dupilumab 200 mg q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Probability at Week 12 | 0.113 probability of LOAC |
| Dupilumab 200 mg q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Probability at Week 24 | 0.113 probability of LOAC |
| Dupilumab 300 mg q4w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Probability at Week 12 | 0.126 probability of LOAC |
| Dupilumab 300 mg q4w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Probability at Week 24 | 0.207 probability of LOAC |
| Dupilumab 200 mg q4w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Probability at Week 12 | 0.052 probability of LOAC |
| Dupilumab 200 mg q4w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population | Probability at Week 24 | 0.162 probability of LOAC |
Secondary
Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population
The time to first LOAC event was defined as the time from the date of first dose to the date of the first LOAC event. For participants who had no LOAC event on or before last dose date + 14 days, it was censored at the date of last dose date + 14 days. The median time to first LOAC was not estimated because the number of LOAC was too low in the Dupilumab arms. Therefore, alternative Kaplan-Meier statistics, the probability of LOAC at Week 12 and 24, are presented as the descriptive measure statistics.
Time frame: Baseline up to Week 24
Population: ITT population. Here 'overall number of participants analyzed' signifies participants of the ITT population who were treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Probability at Week 12 | 0.258 probability of LOAC |
| Placebo q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Probability at Week 24 | 0.338 probability of LOAC |
| Dupilumab 300 mg q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Probability at Week 12 | 0.112 probability of LOAC |
| Dupilumab 300 mg q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Probability at Week 24 | 0.146 probability of LOAC |
| Dupilumab 200 mg q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Probability at Week 12 | 0.09 probability of LOAC |
| Dupilumab 200 mg q2w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Probability at Week 24 | 0.112 probability of LOAC |
| Dupilumab 300 mg q4w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Probability at Week 24 | 0.242 probability of LOAC |
| Dupilumab 300 mg q4w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Probability at Week 12 | 0.145 probability of LOAC |
| Dupilumab 200 mg q4w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Probability at Week 12 | 0.096 probability of LOAC |
| Dupilumab 200 mg q4w | Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population | Probability at Week 24 | 0.209 probability of LOAC |
Secondary
Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population
The time to first severe exacerbation was defined as the time from the date of first dose to the date of the first severe exacerbation event. For participants who had no severe exacerbation on or before last dose date + 14 days, it was censored at the date of last dose date + 14 days. The median time to first severe exacerbation was not estimated because the number of severe exacerbations was too low in the Dupilumab arms. Therefore, alternative Kaplan-Meier statistics, the probability of severe exacerbation at Week 12 and 24, are presented as the descriptive measure statistics.
Time frame: Baseline up to Week 24
Population: HEos-ITT population. Here 'overall number of participants analyzed' signifies participants of the HEos-ITT population who were treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Probability at Week 24 | 0.287 probability of Severe Exacerbation |
| Placebo q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Probability at Week 12 | 0.21 probability of Severe Exacerbation |
| Dupilumab 300 mg q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Probability at Week 24 | 0.116 probability of Severe Exacerbation |
| Dupilumab 300 mg q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Probability at Week 12 | 0.082 probability of Severe Exacerbation |
| Dupilumab 200 mg q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Probability at Week 24 | 0.082 probability of Severe Exacerbation |
| Dupilumab 200 mg q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Probability at Week 12 | 0.082 probability of Severe Exacerbation |
| Dupilumab 300 mg q4w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Probability at Week 12 | 0.094 probability of Severe Exacerbation |
| Dupilumab 300 mg q4w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Probability at Week 24 | 0.175 probability of Severe Exacerbation |
| Dupilumab 200 mg q4w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Probability at Week 24 | 0.125 probability of Severe Exacerbation |
| Dupilumab 200 mg q4w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population | Probability at Week 12 | 0.052 probability of Severe Exacerbation |
Secondary
Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population
The time to first severe exacerbation was defined as the time from the date of first dose to the date of the first severe exacerbation event. For participants who had no severe exacerbation on or before last dose date + 14 days, it was censored at the date of last dose date + 14 days. The median time to first severe exacerbation was not estimated because the number of severe exacerbations was too low in the Dupilumab arms. Therefore, alternative Kaplan-Meier statistics, the probability of severe exacerbation at Week 12 and 24, are presented as the descriptive measure statistics.
Time frame: Baseline up to Week 24
Population: ITT population. Here 'overall number of participants analyzed' signifies participants of ITT population who were treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Probability at Week 24 | 0.266 probability of Severe Exacerbation |
| Placebo q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Probability at Week 12 | 0.207 probability of Severe Exacerbation |
| Dupilumab 300 mg q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Probability at Week 12 | 0.092 probability of Severe Exacerbation |
| Dupilumab 300 mg q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Probability at Week 24 | 0.112 probability of Severe Exacerbation |
| Dupilumab 200 mg q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Probability at Week 24 | 0.091 probability of Severe Exacerbation |
| Dupilumab 200 mg q2w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Probability at Week 12 | 0.07 probability of Severe Exacerbation |
| Dupilumab 300 mg q4w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Probability at Week 12 | 0.112 probability of Severe Exacerbation |
| Dupilumab 300 mg q4w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Probability at Week 24 | 0.195 probability of Severe Exacerbation |
| Dupilumab 200 mg q4w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Probability at Week 24 | 0.16 probability of Severe Exacerbation |
| Dupilumab 200 mg q4w | Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population | Probability at Week 12 | 0.075 probability of Severe Exacerbation |
Post Hoc
Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L
FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time frame: Baseline, Week 12
Population: Analysis was performed on subset of ITT population which included participants with baseline blood eosinophil count \<0.3 G/L.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Week 12 | 1.92 liter | Standard Deviation 0.61 |
| Placebo q2w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Baseline | 1.79 liter | Standard Deviation 0.42 |
| Placebo q2w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Change from baseline at Week 12 | 0.09 liter | Standard Deviation 0.36 |
| Dupilumab 300 mg q2w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Baseline | 1.9 liter | Standard Deviation 0.55 |
| Dupilumab 300 mg q2w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Week 12 | 2.12 liter | Standard Deviation 0.63 |
| Dupilumab 300 mg q2w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Change from baseline at Week 12 | 0.19 liter | Standard Deviation 0.31 |
| Dupilumab 200 mg q2w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Change from baseline at Week 12 | 0.23 liter | Standard Deviation 0.33 |
| Dupilumab 200 mg q2w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Week 12 | 2.02 liter | Standard Deviation 0.67 |
| Dupilumab 200 mg q2w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Baseline | 1.79 liter | Standard Deviation 0.53 |
| Dupilumab 300 mg q4w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Week 12 | 2.05 liter | Standard Deviation 0.68 |
| Dupilumab 300 mg q4w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Baseline | 1.85 liter | Standard Deviation 0.56 |
| Dupilumab 300 mg q4w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Change from baseline at Week 12 | 0.16 liter | Standard Deviation 0.36 |
| Dupilumab 200 mg q4w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Change from baseline at Week 12 | 0.17 liter | Standard Deviation 0.36 |
| Dupilumab 200 mg q4w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Baseline | 1.94 liter | Standard Deviation 0.56 |
| Dupilumab 200 mg q4w | Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L | Week 12 | 2.06 liter | Standard Deviation 0.68 |