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CompletedNCT01854047Updated Jun 26, 2017Results posted

An Evaluation of Dupilumab in Patients With Moderate to Severe Uncontrolled Asthma

A Phase 2 interventional study of Dupilumab and placebo in Asthma, sponsored by Sanofi. Completed at 201 sites in 16 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-06-26.

Sponsored by Sanofi · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
776
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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
Read the 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).

02

Conditions studied

  • Asthma

Browse trials for

03

In context

Asthma

3,921 studies on the registry are indexed under Asthma; 507 are open to participants now.

This study's enrollment of 776 is above the median of 83 across 2,752 interventional studies indexed under Asthma.

Browse Asthma studies →

Lead sponsor

Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.

Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
776 participants (actual)

Study arms

  • Experimental
    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 inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Drug: Dupilumab · Drug: ICS/LABA therapy · Drug: Salbutamol/albuterol · Drug: Levosalbutamol/levalbuterol

  • Experimental
    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.

    Drug: Dupilumab · Drug: ICS/LABA therapy · Drug: Salbutamol/albuterol · Drug: Levosalbutamol/levalbuterol

  • Experimental
    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.

    Drug: Dupilumab · Drug: placebo · Drug: ICS/LABA therapy · Drug: Salbutamol/albuterol · Drug: Levosalbutamol/levalbuterol

  • Experimental
    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.

    Drug: Dupilumab · Drug: placebo · Drug: ICS/LABA therapy · Drug: Salbutamol/albuterol · Drug: Levosalbutamol/levalbuterol

  • Placebo comparator
    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.

    Drug: placebo · Drug: ICS/LABA therapy · Drug: Salbutamol/albuterol · Drug: Levosalbutamol/levalbuterol

Interventions

  • DrugDupilumab

    Solution for injection, Subcutaneous injection

    Also known as: SAR231893, REGN668

  • 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

  • DrugSalbutamol/albuterol

    Oral inhalation as needed

  • DrugLevosalbutamol/levalbuterol

    Oral inhalation as needed

06

What researchers measure

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

07

Results

Posted Jun 2, 2017

Participant flow

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.

Participant flow — Overall Study
MilestonePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Started158157150157154
Treated158156148157150
Completed 12-week study treatment153149141146143
Completed146149137142135
Not completed128131519
Withdrew: Lack of efficacy10000
Withdrew: Poor compliance to protocol30200
Withdrew: Adverse event546107
Withdrew: Randomized but not treated01204
Withdrew: Other than specified above33358

Outcome measures

PrimaryAbsolute 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
Reported as:
Mean · liter
Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population
literPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline1.86 ± 0.681.77 ± 0.51.8 ± 0.521.87 ± 0.61.8 ± 0.49
Week 122.13 ± 0.782.12 ± 0.542.26 ± 0.682.26 ± 0.702.09 ± 0.54
Change from baseline at Week 120.18 ± 0.380.36 ± 0.460.45 ± 0.400.35 ± 0.430.26 ± 0.47
Statistical analysis
  • Placebo q2w vs Dupilumab 300 mg q2w · Mixed Models Analysis · p = 0.0063 (Threshold for significance at 0.05.) · Least square (ls) mean difference: 0.21 · 95% CI 0.06 to 0.36Dupilumab 300 mg q2w vs. Placebo q2w
  • Placebo q2w vs Dupilumab 200 mg q2w · Mixed Models Analysis · p = 0.0008 (Threshold for significance at 0.05.) · Ls mean difference: 0.26 · 95% CI 0.11 to 0.40Dupilumab 200 mg q2w vs. Placebo q2w
  • Placebo q2w vs Dupilumab 300 mg q4w · Mixed Models Analysis · p = 0.0212 (Threshold for significance at 0.05.) · Ls mean difference: 0.17 · 95% CI 0.03 to 0.32Dupilumab 300 mg q4w vs. Placebo q2w
  • Placebo q2w vs Dupilumab 200 mg q4w · Mixed Models Analysis · p = 0.2774 (Threshold for significance at 0.05.) · Ls mean difference: 0.08 · 95% CI -0.07 to 0.23Dupilumab 200 mg q4w vs. Placebo q2w
PrimaryAbsolute 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
Reported as:
Mean · liter
Absolute Change From Baseline in FEV1 at Week 12: ITT Population
literPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline1.82 ± 0.551.85 ± 0.531.79 ± 0.521.86 ± 0.571.88 ± 0.54
Week 122.01 ± 0.692.12 ± 0.592.12 ± 0.682.14 ± 0.692.07 ± 0.63
Change from baseline at Week 120.13 ± 0.370.26 ± 0.390.32 ± 0.380.24 ± 0.40.20 ± 0.41
Statistical analysis
  • Placebo q2w vs Dupilumab 300 mg q2w · Mixed Models Analysis · p = 0.0002 (Threshold for significance at 0.05.) · Ls mean difference: 0.16 · 95% CI 0.08 to 0.25Dupilumab 300 mg q2w vs. Placebo q2w
  • Placebo q2w vs Dupilumab 200 mg q2w · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05.) · Ls mean difference: 0.2 · 95% CI 0.011 to 0.28Dupilumab 200 mg q2w vs. Placebo q2w
  • Placebo q2w vs Dupilumab 300 mg q4w · Mixed Models Analysis · p = 0.0048 (Threshold for significance at 0.05.) · Ls mean difference: 0.12 · 95% CI 0.04 to 0.21Dupilumab 300 mg q4w vs. Placebo q2w
  • Placebo q2w vs Dupilumab 200 mg q4w · Mixed Models Analysis · p = 0.0304 (Threshold for significance at 0.05.) · Ls mean difference: 0.10 · 95% CI 0.01 to 0.18Dupilumab 200 mg q4w vs. Placebo q2w
SecondaryPercent 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
Reported as:
Mean · percent change
Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population
percent changePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population10.07 ± 19.6525.29 ± 36.1527.42 ± 25.6820.68 ± 24.8618.07 ± 29.18
SecondaryPercent 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
Reported as:
Mean · percent change
Percent Change From Baseline in FEV1 at Week 12: ITT Population
percent changePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Percent Change From Baseline in FEV1 at Week 12: ITT Population7.04 ± 19.2616.64 ± 27.7819.15 ± 23.5313.55 ± 23.0113.04 ± 24.21
SecondaryAnnualized 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
Reported as:
Number · exacerbation per participant-year
Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population
exacerbation per participant-yearPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population1.044 (0.572 to 1.904)0.201 (0.078 to 0.517)0.30 (0.133 to 0.678)0.678 (0.356 to 1.29)0.358 (0.158 to 0.809)
SecondaryAnnualized 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
Reported as:
Number · exacerbation per participant-year
Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population
exacerbation per participant-yearPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population0.897 (0.619 to 1.30)0.265 (0.157 to 0.445)0.269 (0.157 to 0.461)0.599 (0.369 to 0.907)0.415 (0.26 to 0.664)
SecondaryTime 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
Reported as:
Number · probability of Severe Exacerbation
Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population
probability of Severe ExacerbationPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Probability at Week 120.21 (0.122 to 0.314)0.082 (0.03 to 0.167)0.082 (0.03 to 0.167)0.094 (0.038 to 0.181)0.052 (0.014 to 0.13)
Probability at Week 240.287 (0.184 to 0.398)0.116 (0.051 to 0.21)0.082 (0.03 to 0.167)0.175 (0.093 to 0.278)0.125 (0.055 to 0.226)
SecondaryTime 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
Reported as:
Number · probability of Severe Exacerbation
Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population
probability of Severe ExacerbationPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Probability at Week 120.207 (0.147 to 0.274)0.092 (0.053 to 0.145)0.07 (0.036 to 0.119)0.112 (0.068 to 0.168)0.075 (0.04 to 0.125)
Probability at Week 240.266 (0.199 to 0.338)0.112 (0.068 to 0.169)0.091 (0.051 to 0.145)0.195 (0.136 to 0.262)0.16 (0.106 to 0.225)
SecondaryAnnualized 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
Reported as:
Number · LOAC per participant-year
Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population
LOAC per participant-yearPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population1.312 (0.804 to 2.142)0.322 (0.153 to 0.677)0.446 (0.231 to 0.864)0.788 (0.458 to 1.355)0.424 (0.212 to 0.851)
SecondaryAnnualized 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
Reported as:
Number · LOAC per participant-year
Annualized Event Rate of LOAC During The Treatment Period: ITT Population
LOAC per participant-yearPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Annualized Event Rate of LOAC During The Treatment Period: ITT Population1.107 (0.801 to 1.53)0.326 (0.206 to 0.515)0.347 (0.217 to 0.555)0.73 (0.508 to 1.048)0.563 (0.378 to 0.839)
SecondaryTime 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
Reported as:
Number · probability of LOAC
Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population
probability of LOACPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Probability at Week 120.30 (0.195 to 0.411)0.115 (0.05 to 0.208)0.113 (0.05 to 0.206)0.126 (0.059 to 0.22)0.052 (0.014 to 0.13)
Probability at Week 240.392 (0.275 to 0.507)0.166 (0.085 to 0.269)0.113 (0.05 to 0.206)0.207 (0.117 to 0.314)0.162 (0.079 to 0.269)
SecondaryTime 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
Reported as:
Number · probability of LOAC
Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population
probability of LOACPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Probability at Week 120.258 (0.192 to 0.329)0.112 (0.068 to 0.168)0.09 (0.051 to 0.144)0.145 (0.095 to 0.206)0.096 (0.055 to 0.15)
Probability at Week 240.338 (0.265 to 0.413)0.146 (0.095 to 0.207)0.112 (0.067 to 0.169)0.242 (0.177 to 0.314)0.209 (0.147 to 0.279)
SecondaryChange 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
Reported as:
Mean · scores on a scale
Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population
scores on a scalePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline1.15 ± 0.821.45 ± 0.811.22 ± 0.811.31 ± 0.721.18 ± 0.82
Week 120.83 ± 0.660.78 ± 0.880.70 ± 0.690.70 ± 0.780.63 ± 0.62
Change from baseline at Week 12-0.29 ± 0.70-0.66 ± 0.67-0.55 ± 0.75-0.57 ± 0.63-0.57 ± 0.60
SecondaryChange 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
Reported as:
Mean · scores on a scale
Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population
scores on a scalePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline1.17 ± 0.791.25 ± 0.781.24 ± 0.811.33 ± 0.781.29 ± 0.82
Week 120.90 ± 0.670.82 ± 0.790.79 ± 0.770.80 ± 0.730.72 ± 0.68
Change from baseline at Week 12-0.23 ± 0.70-0.43 ± 0.70-0.46 ± 0.75-0.52 ± 0.65-0.54 ± 0.64
SecondaryChange 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
Reported as:
Mean · scores on a scale
Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population
scores on a scalePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline1.33 ± 0.831.72 ± 0.891.46 ± 0.731.52 ± 0.721.39 ± 0.87
Week 120.95 ± 0.710.88 ± 0.910.89 ± 0.790.76 ± 0.840.69 ± 0.68
Change from baseline at Week 12-0.35 ± 0.71-0.84 ± 0.87-0.62 ± 0.70-0.73 ± 0.77-0.69 ± 0.70
SecondaryChange 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
Reported as:
Mean · scores on a scale
Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population
scores on a scalePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline1.32 ± 0.811.47 ± 0.851.42 ± 0.791.50 ± 0.741.47 ± 0.84
Week 121.02 ± 0.730.95 ± 0.880.95 ± 0.810.89 ± 0.790.89 ± 0.81
Change from baseline at Week 12-0.27 ± 0.76-0.52 ± 0.79-0.52 ± 0.80-0.59 ± 0.79-0.54 ± 0.71
SecondaryChange 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
Reported as:
Mean · scores on a scale
Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population
scores on a scalePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline2.55 ± 0.842.98 ± 0.902.65 ± 0.742.69 ± 0.812.76 ± 0.91
Week 121.52 ± 1.091.20 ± 0.961.20 ± 0.881.27 ± 0.911.39 ± 0.94
Change from baseline at Week 12-1.03 ± 0.93-1.72 ± 1.14-1.40 ± 1.03-1.39 ± 1.02-1.38 ± 0.90
SecondaryChange 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
Reported as:
Mean · scores on a scale
Change From Baseline in ACQ-5 Score at Week 12: ITT Population
scores on a scalePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline2.69 ± 0.802.80 ± 0.832.73 ± 0.822.70 ± 0.792.78 ± 0.84
Week 121.55 ± 1.001.41 ± 1.021.38 ± 0.961.38 ± 0.861.49 ± 0.98
Change from baseline at Week 12-1.11 ± 0.93-1.38 ± 1.10-1.35 ± 1.05-1.32 ± 1.02-1.24 ± 0.95
SecondaryChange 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
Reported as:
Mean · scores on a scale
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population
scores on a scalePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline4.16 ± 1.273.82 ± 1.134.02 ± 1.153.99 ± 1.063.89 ± 1.88
Week 125.05 ± 1.225.35 ± 1.215.41 ± 1.065.06 ± 1.195.05 ± 1.29
Change from baseline at Week 120.80 ± 1.021.54 ± 1.181.42 ± 0.971.08 ± 0.971.16 ± 1.01
SecondaryChange 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
Reported as:
Mean · scores on a scale
Change From Baseline in AQLQ Global Score at Week 12: ITT Population
scores on a scalePlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline4.12 ± 1.103.91 ± 1.134.03 ± 1.154.02 ± 1.014.00 ± 1.09
Week 125.00 ± 1.105.13 ± 1.225.22 ± 1.115.04 ± 1.135.03 ± 1.12
Change from baseline at Week 120.86 ± 0.991.25 ± 1.101.19 ± 1.051.03 ± 1.020.98 ± 1.02
SecondaryChange 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
Reported as:
Mean · inhalations per day
Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population
inhalations per dayPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline2.53 ± 2.773.61 ± 3.563.02 ± 2.853.15 ± 2.702.42 ± 2.75
Week 121.88 ± 2.532.14 ± 3.222.15 ± 2.671.85 ± 2.751.36 ± 1.76
Change from baseline at Week 12-0.51 ± 1.74-1.47 ± 2.31-0.93 ± 2.31-1.49 ± 2.37-1.01 ± 2.00
SecondaryChange 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
Reported as:
Mean · inhalations per day
Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population
inhalations per dayPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline2.72 ± 2.733.25 ± 3.152.98 ± 2.743.36 ± 3.433.01 ± 2.87
Week 122.20 ± 2.572.30 ± 3.022.03 ± 2.462.09 ± 2.731.99 ± 2.42
Change from baseline at Week 12-0.44 ± 1.75-0.95 ± 2.05-0.99 ± 2.27-1.35 ± 2.84-0.92 ± 2.16
Post-hocChange 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
Reported as:
Mean · liter
Change From Baseline in FEV1 at Week 12: Subset of ITT Population With Baseline Blood Eosinophil <0.3 G/L
literPlacebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Baseline1.79 ± 0.421.9 ± 0.551.79 ± 0.531.85 ± 0.561.94 ± 0.56
Week 121.92 ± 0.612.12 ± 0.632.02 ± 0.672.05 ± 0.682.06 ± 0.68
Change from baseline at Week 120.09 ± 0.360.19 ± 0.310.23 ± 0.330.16 ± 0.360.17 ± 0.36

Adverse events

Collected over All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 40) regardless of seriousness or relationship to investigational product.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/158 (0%)9/158 (5.7%)88/158 (55.7%)
Dupilumab 300 mg q2w0/156 (0%)13/156 (8.3%)95/156 (60.9%)
Dupilumab 200 mg q2w0/148 (0%)10/148 (6.8%)81/148 (54.7%)
Dupilumab 300 mg q4w2/157 (1.3%)16/157 (10.2%)96/157 (61.1%)
Dupilumab 200 mg q4w0/150 (0%)6/150 (4%)74/150 (49.3%)
Most frequent serious events
Showing 10 of 45
Most frequent serious events
EventPlaceboDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
AsthmaRespiratory, thoracic and mediastinal disorders4/1581/1565/1482/1572/150
Abortion spontaneousPregnancy, puerperium and perinatal conditions0/1580/1562/1481/1570/150
GastroenteritisInfections and infestations0/1582/1560/1480/1570/150
EpiglottitisInfections and infestations0/1580/1561/1480/1570/150
SinusitisInfections and infestations0/1580/1561/1480/1570/150
HypertensionVascular disorders0/1580/1561/1480/1570/150
ColitisGastrointestinal disorders0/1580/1561/1480/1570/150
Procedural painInjury, poisoning and procedural complications0/1580/1561/1480/1570/150
Benign neoplasm of thyroid glandNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1580/1560/1480/1571/150
Atrioventricular block completeCardiac disorders0/1580/1560/1480/1571/150
Most frequent other events
Showing 10 of 15
Most frequent other events
EventPlaceboDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4w
Injection site erythemaGeneral disorders12/15834/15621/14812/15713/150
Upper respiratory tract infectionInfections and infestations28/15820/15622/14819/15722/150
HeadacheNervous system disorders20/15817/15617/14819/1579/150
BronchitisInfections and infestations16/15819/15611/14811/15710/150
NasopharyngitisInfections and infestations15/15816/15615/14819/1579/150
Injection site painGeneral disorders7/15814/1567/1486/1575/150
InfluenzaInfections and infestations5/1589/1566/14813/15710/150
SinusitisInfections and infestations11/1586/1565/14813/15712/150
Back painMusculoskeletal and connective tissue disorders6/15812/1568/1484/1577/150
Injection site pruritusGeneral disorders5/15812/15610/1480/1573/150

Baseline characteristics

Age, Continuous
Age, Continuous(years)Placebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4wTotal
Mean49 ± 12.747.5 ± 12.451 ± 13.447.9 ± 13.147.9 ± 13.148.6 ± 13.0
Sex: Female, Male
Sex: Female, Male(Participants)Placebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4wTotal
Female1041039610087490
Male5454545767286
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Placebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4wTotal
American Indian or Alaska Native001001
Asian2522252320115
Native Hawaiian or Other Pacific Islander000101
Black or African American95912742
White119129114120125607
More than one race000000
Unknown or Not Reported5111210
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Placebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4wTotal
Hispanic Or Latino3129293326148
Not Hispanic Or Latino127128121124128628
Number of Participants According to Blood Eosinophil Count
Number of Participants According to Blood Eosinophil Count(Participants)Placebo q2wDupilumab 300 mg q2wDupilumab 200 mg q2wDupilumab 300 mg q4wDupilumab 200 mg q4wTotal
<0.3 G/L9093859192451
>=0.3 G/L6864656662325
08

Study locations

201 sites
  • Investigational Site Number 840050
    Fullerton, California 92835, United States
  • Investigational Site Number 840041
    Huntington Beach, California 92647, United States
  • Investigational Site Number 840019
    Los Angeles, California 90025, United States
  • Investigational Site Number 840029
    Los Angeles, California 90025, United States
  • Investigational Site Number 840022
    Los Angeles, California 90048, United States
  • Investigational Site Number 840013
    Mission Viejo, California 92691, United States
  • Investigational Site Number 840044
    Newport Beach, California 92663, United States
  • Investigational Site Number 840007
    Riverside, California 92506, United States
  • Investigational Site Number 840014
    Rolling Hills Estates, California 90274, United States
  • Investigational Site Number 840036
    San Jose, California 95117, United States
  • Investigational Site Number 840032
    Colorado Springs, Colorado 80907, United States
  • Investigational Site Number 840040
    Colorado Springs, Colorado 80907, United States
  • Investigational Site Number 840043
    Denver, Colorado 80206, United States
  • Investigational Site Number 840006
    Denver, Colorado 80230, United States
  • Investigational Site Number 840024
    Denver, Colorado 80230, United States
  • Investigational Site Number 840027
    Daytona Beach, Florida 32117, United States
  • Investigational Site Number 840039
    Miami, Florida 33135, United States
  • Investigational Site Number 840048
    Albany, Georgia 31707, United States
  • Investigational Site Number 840026
    River Forest, Illinois 60305, United States
  • Investigational Site Number 840053
    Evansville, Indiana 47713, United States
  • Investigational Site Number 840017
    Louisville, Kentucky 40223-5440, United States
  • Investigational Site Number 840030
    Owensboro, Kentucky 42303, United States
  • Investigational Site Number 840028
    Baltimore, Maryland 21287, United States
  • Investigational Site Number 840052
    Wheaton, Maryland 20902, United States
  • Investigational Site Number 840045
    North Dartmouth, Massachusetts 02747, United States
  • Investigational Site Number 840046
    Novi, Michigan 48375, United States
  • Investigational Site Number 840051
    Novi, Michigan 48375, United States
  • Investigational Site Number 840018
    Minneapolis, Minnesota 55402, United States
  • Investigational Site Number 840002
    Saint Louis, Missouri 63110, United States
  • Investigational Site Number 840003
    Saint Louis, Missouri 63141, United States
  • Investigational Site Number 840037
    Missoula, Montana 59804, United States
  • Investigational Site Number 840004
    Papillion, Nebraska 27103, United States
  • Investigational Site Number 840011
    Princeton, New Jersey 08540, United States
  • Investigational Site Number 840016
    Rochester, New York 14618, United States
  • Investigational Site Number 840025
    Cincinnati, Ohio 45231, United States
  • Investigational Site Number 840015
    Cincinnati, Ohio 45236, United States
  • Investigational Site Number 840020
    Cincinnati, Ohio 45241, United States
  • Investigational Site Number 840001
    Oklahoma City, Oklahoma 73120, United States
  • Investigational Site Number 840031
    Lake Oswego, Oregon 97035, United States
  • Investigational Site Number 840034
    Medford, Oregon 97504, United States
  • Investigational Site Number 840042
    Philadelphia, Pennsylvania 19107, United States
  • Investigational Site Number 840010
    Pittsburgh, Pennsylvania 15213, United States
  • Investigational Site Number 840009
    Upland, Pennsylvania 19013, United States
  • Investigational Site Number 840021
    Spartanburg, South Carolina 29303, United States
  • Investigational Site Number 840023
    Dallas, Texas 75231, United States
  • Investigational Site Number 840005
    El Paso, Texas 79902, United States
  • Investigational Site Number 840008
    San Antonio, Texas 78229, United States
  • Investigational Site Number 840035
    Richmond, Virginia 23225, United States
  • Investigational Site Number 840054
    Everett, Washington 98203, United States
  • Investigational Site Number 840033
    Tacoma, Washington 98405, United States
  • Investigational Site Number 032004
    Buenos Aires, B6500BWQ, Argentina
  • Investigational Site Number 032003
    Buenos Aires, C1121ABE, Argentina
  • Investigational Site Number 032008
    Caba, 1424, Argentina
  • Investigational Site Number 032010
    Caba, 1425, Argentina
  • Investigational Site Number 032001
    Caba, Argentina
  • Investigational Site Number 032002
    La Plata, 1900, Argentina
  • Investigational Site Number 032005
    Rosario, 2000, Argentina
  • Investigational Site Number 032006
    Rosario, 2000, Argentina
  • Investigational Site Number 032007
    Rosario, 2000, Argentina
  • Investigational Site Number 032012
    Santa Fe, 3000, Argentina
  • Investigational Site Number 032009
    Tucumán, 4000, Argentina
  • Investigational Site Number 036004
    Adelaide, 5000, Australia
  • Investigational Site Number 036002
    Brisbane, 4101, Australia
  • Investigational Site Number 036005
    Campbelltown, 2560, Australia
  • Investigational Site Number 036001
    Clayton, 3168, Australia
  • Investigational Site Number 036008
    Frankston, 3199, Australia
  • Investigational Site Number 036003
    Nedlands, 6009, Australia
  • Investigational Site Number 036009
    Prahran, 3004, Australia
  • Investigational Site Number 036006
    Woolloongabba, 4102, Australia
  • Investigational Site Number 152007
    Quillota, 226000, Chile
  • Investigational Site Number 152011
    Santiago, 00000, Chile
  • Investigational Site Number 152001
    Santiago, 7500710, Chile
  • Investigational Site Number 152002
    Santiago, 8380456, Chile
  • Investigational Site Number 152014
    Santiago, 8910131, Chile
  • Investigational Site Number 152003
    Santiago, Chile
  • Investigational Site Number 152005
    Santiago, Chile
  • Investigational Site Number 152012
    Santiago, Chile
  • Investigational Site Number 152013
    Santiago, Chile
  • Investigational Site Number 152008
    Talca, Chile
  • Investigational Site Number 152006
    Viña Del Mar, Chile
  • Investigational Site Number 250009
    Brest Cedex, 29610, France
  • Investigational Site Number 250004
    Grenoble Cedex 09, 38043, France
  • Investigational Site Number 250010
    Lille, 59037, France
  • Investigational Site Number 250006
    Lyon, 69317, France
  • Investigational Site Number 250001
    Marseille, 13915, France
  • Investigational Site Number 250002
    Montpellier, 34295, France
  • Investigational Site Number 250005
    Nantes, 44093, France
  • Investigational Site Number 250007
    Nimes, 30029, France
  • Investigational Site Number 250003
    Pessac, 33604, France
  • Investigational Site Number 250008
    Strasbourg, 67091, France
  • Investigational Site Number 250011
    Vernon, 27200, France
  • Investigational Site Number 380010
    Ancona, 60126, Italy
  • Investigational Site Number 380009
    Catania, 95123, Italy
  • Investigational Site Number 380004
    Ferrara, 44121, Italy
  • Investigational Site Number 380002
    Firenze, 50134, Italy
  • Investigational Site Number 380008
    Foggia, 71100, Italy
  • Investigational Site Number 380003
    Modena, 41124, Italy
  • Investigational Site Number 380007
    Padova, 35128, Italy
  • Investigational Site Number 380001
    Pisa, 56100, Italy
  • Investigational Site Number 380005
    Torino, 10126, Italy

Showing the first 100 of 201 sites across 16 countries.

09

References and documents

Publications

  • Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, Pirozzi G, Sutherland ER, Evans RR, Joish VN, Eckert L, Graham NM, Stahl N, Yancopoulos GD, Louis-Tisserand M, Teper A. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting beta2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016 Jul 2;388(10039):31-44. doi: 10.1016/S0140-6736(16)30307-5. Epub 2016 Apr 27. PubMed 27130691 ↗
  • Wechsler ME, Klion AD, Paggiaro P, Nair P, Staumont-Salle D, Radwan A, Johnson RR, Kapoor U, Khokhar FA, Daizadeh N, Chen Z, Laws E, Ortiz B, Jacob-Nara JA, Mannent LP, Rowe PJ, Deniz Y. Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2022 Oct;10(10):2695-2709. doi: 10.1016/j.jaip.2022.05.019. Epub 2022 May 28. PubMed 35636689 ↗
  • Bourdin A, Papi AA, Corren J, Virchow JC, Rice MS, Deniz Y, Djandji M, Rowe P, Pavord ID. Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline. Allergy. 2021 Jan;76(1):269-280. doi: 10.1111/all.14611. Epub 2020 Oct 21. PubMed 33010038 ↗
  • Maspero JF, Katelaris CH, Busse WW, Castro M, Corren J, Chipps BE, Peters AT, Pavord ID, Ford LB, Sher L, Rabe KF, Rice MS, Rowe P, Lu Y, Harel S, Jagerschmidt A, Khan AH, Kamat S, Pirozzi G, Amin N, Ruddy M, Graham NMH, Mannent LP, Teper A. Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2020 Feb;8(2):527-539.e9. doi: 10.1016/j.jaip.2019.07.016. Epub 2019 Jul 24. PubMed 31351189 ↗
  • Corren J, Castro M, Ford LB, Bernstein JA, Jayawardena S, Maroni J, Rowe P, Amin N, Pirozzi G, Graham NMH, Khan A, Eckert L, Teper A. Dupilumab improves asthma outcomes irrespective of frequency of previous asthma exacerbation history. Ann Allergy Asthma Immunol. 2019 Aug;123(2):222-224.e1. doi: 10.1016/j.anai.2019.04.028. Epub 2019 May 8. No abstract available. PubMed 31075309 ↗
  • Corren J, Castro M, Chanez P, Fabbri L, Joish VN, Amin N, Graham NMH, Mastey V, Abbe A, Taniou C, Mahajan P, Teper A, Pirozzi G, Eckert L. Dupilumab improves symptoms, quality of life, and productivity in uncontrolled persistent asthma. Ann Allergy Asthma Immunol. 2019 Jan;122(1):41-49.e2. doi: 10.1016/j.anai.2018.08.005. Epub 2018 Aug 21. PubMed 30138668 ↗
  • Weinstein SF, Katial R, Jayawardena S, Pirozzi G, Staudinger H, Eckert L, Joish VN, Amin N, Maroni J, Rowe P, Graham NMH, Teper A. Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma. J Allergy Clin Immunol. 2018 Jul;142(1):171-177.e1. doi: 10.1016/j.jaci.2017.11.051. Epub 2018 Jan 31. PubMed 29355679 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 26, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01854047
Lead sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
Responsible party
Sponsor
First posted
May 15, 2013
Start date
Jun 2013
Primary completion
Nov 2014
Completion
Apr 2015
Results posted
Jun 2, 2017
Last update
Jun 26, 2017

Study contacts

Clinical Sciences & Operations
study director · Sanofi

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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