Asthma
Conditions
Brief summary
Primary Objective: To evaluate the effect of dupilumab, compared to placebo, on airway inflammation in participants with persistent asthma. Secondary Objective: To assess the safety, tolerability, and immunogenicity of dupilumab compared to placebo.
Detailed description
The total study duration for each participant was between approximately 29 and maximum of 30 weeks, consisting of a screening period of 5 weeks and optional up to 7 additional days, a treatment period of 12 weeks, and a post-treatment period of 12 weeks. Participants who completed the treatment period could be eligible to participate in an open-label extension study.
Interventions
DRUGPlacebo
Pharmaceutical form:solution Route of administration: subcutaneous
DRUGDupilumab SAR231893/REGN668
Pharmaceutical form:solution Route of administration: subcutaneous
Pharmaceutical form:inhalation aerosol, inhalation powder Route of administration: inhaled
Pharmaceutical form:inhalation aerosol Route of administration: inhaled
DRUGmometasone furoate and formoterol
Pharmaceutical form:inhalation aerosol Route of administration: inhaled
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female adults with a physician diagnosis of persistent asthma for ≥12 months. * Existing treatment with medium to high dose inhaled corticosteroids in combination with a long-acting beta agonist for at least 3 months with a stable dose ≥1 month prior to Visit 1 (Screening Visit). * Treatment with a third asthma controller for at least 3 months with a stable dose \>=1 month prior to Visit 1 was allowed. * Pre-bronchodilator forced expiratory volume (FEV1) 55 to 85% of predicted normal.
Exclusion criteria
* Participants \<18 years or \>65 years. * Fractional exhaled nitric oxide (FeNO) \<26 parts per billion (ppb) at Visit 1 (Screening Visit). * Chronic obstructive pulmonary disease or other lung diseases (eg, idiopathic pulmonary fibrosis, eosinophilic granulomatosis with polyangiitis \[Churg-Strauss Syndrome\]) which could impair lung function. * A participant who experienced an asthma exacerbation that resulted in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids at any time from 1 month prior to Visit 1. * A participant who had experienced an upper or lower respiratory tract infection within the 4 weeks prior to Visit 1. * Evidence of lung disease(s) other than asthma. * Previous smoker (smoking history \>10 pack-years) or current smoker (within 6 months prior to Visit 1). * Comorbid disease that might interfere with the evaluation of investigational medicinal product or conduct of study procedures (e.g., bronchoscopy). * Anti-immunoglobulin E (IgE) therapy (omalizumab) or any other biologic therapy within 6 months of Visit 1. * Exposure to another investigative study medication within a time period prior to Visit 1 that is less than 5 half-lives of the study medication. * Treatment with systemic (oral or injectable) corticosteroids within 28 days of Visit 1. 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 |
|---|---|---|
| Change From Baseline in T-Helper Lymphocytes Count in the Bronchial Submucosa at Week 12 | Baseline, Week 12 | T-helper i.e. CD4 positive lymphocytes were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter. |
| Change From Baseline in Eosinophils Cells Count in the Bronchial Submucosa at Week 12 | Baseline, Week 12 | Inflammatory cells i.e. eosinophils were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter. |
| Change From Baseline in Mucin-Stained Area in the Bronchial Submucosa at Week 12 | Baseline, Week 12 | Mucin was identified by staining with Alcian-blue periodic acid-Schiff and/or immunostaining for MUC5AC and then the mucin-positive area was measured and expressed per square millimeter. |
| Change From Baseline in Mast Cells Count (Chymase Positive) in the Bronchial Submucosa at Week 12 | Baseline, Week 12 | Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter. |
| Change From Baseline in Mast Cells Count (Tryptase Positive) in the Bronchial Submucosa at Week 12 | Baseline, Week 12 | Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter. |
| Change From Baseline in T-Lymphocytes Count in the Bronchial Submucosa at Week 12 | Baseline, Week 12 | T-Lymphocytes i.e. CD3 positive cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 6 Through Week 12 | From Baseline to Week 6 through Week 12 | FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/s, and reported in ppb. The average change in FeNO from baseline to Week 6 through Week 12 was calculated as follows: For each participant the change in FeNO from Baseline to Week 6, Week 8, Week 10 and Week 12 was calculated (value at Week X - value at baseline). Subsequently the weekly mean of these 4 change from baseline values was determined (Weeks 6, 8, 10 and 12). Using these weekly mean values the overall arithmetic mean and standard deviation of the average change in FeNO from baseline to Week 6 through Week 12 was calculated. |
| Number of Participants With Antidrug Antibodies (ADA) | From Baseline up to 24 weeks | Anti-drug antibodies were detected using a validated immunoassay. Incidence of ADA were classified as following: 1) Pre-existing immunoreactivity - an ADA positive response in the assay at baseline with all post treatment ADA results negative or an ADA positive response at baseline with all post treatment ADA responses less than 4-fold over baseline titer levels. 2) Treatment-emergent ADA: an ADA positive response in the assay post first dose, when baseline results were negative or missing. 3) Treatment-boosted ADA: an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive. |
| Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration | Week 0, Week 2, 6, 8, 12, 18, End of study (Week 24) | Serum functional dupilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Baseline up to Week 24 | Adverse event (AE) was defined as any untoward medical occurrence in a participant who received investigational medicinal product (IMP) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during between the first administration of study medication to the end of the 12 week Post-treatment Period. Serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included both serious and non-serious AEs. |
| Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12 | Baseline, Week 12 | FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/second, and reported in ppb. |
Countries
Canada, Denmark, Germany, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 16 sites in 6 countries. A total of 133 participants were screened between January 2016 and January 2018. Of which, 42 participants were randomized. 91 participants were screen failures mainly due to exclusion criteria met and inclusion criteria not met.
Pre-assignment details
Participants were randomized in 1:1 ratio to receive dupilumab 300 mg every 2 weeks (q2w) and placebo q2w by using Interactive Voice/Web Response System (IVRS). Randomization was stratified by inhaled corticosteroids (ICS) dose (medium and high) and region (North America and Europe).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | 22 |
| Dupilumab Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication. | 20 |
| Total | 42 |
Baseline characteristics
| Characteristic | Placebo | Total | Dupilumab |
|---|---|---|---|
| Age, Continuous | 41.0 years STANDARD_DEVIATION 10.3 | 43.1 years STANDARD_DEVIATION 10.6 | 45.5 years STANDARD_DEVIATION 10.6 |
| Baseline Eosinophils Count in Bronchial Tissue | 12.97 cells/mm^2 | 20.73 cells/mm^2 | 34.96 cells/mm^2 |
| Baseline Fractional exhaled nitric oxide (FeNO) | 41.2 parts per billion (ppb) STANDARD_DEVIATION 31.5 | 38.9 parts per billion (ppb) STANDARD_DEVIATION 27.5 | 36.4 parts per billion (ppb) STANDARD_DEVIATION 22.8 |
| Baseline Mast Cells Count (Chymase Positive) in Bronchial Tissue | 74.36 cells/mm^2 STANDARD_DEVIATION 58.63 | 76.59 cells/mm^2 STANDARD_DEVIATION 62.42 | 79.17 cells/mm^2 STANDARD_DEVIATION 68.07 |
| Baseline Mast Cells Count (Tryptase Positive) in Bronchial Tissue | 80.10 cells/mm^2 STANDARD_DEVIATION 64.92 | 91.88 cells/mm^2 STANDARD_DEVIATION 85.49 | 105.53 cells/mm^2 STANDARD_DEVIATION 104.68 |
| Baseline Mucin-Stained Area in The Bronchial Tissue Specimen | 561.12 cells/mm^2 STANDARD_DEVIATION 289 | 542.33 cells/mm^2 STANDARD_DEVIATION 402.61 | 520.57 cells/mm^2 STANDARD_DEVIATION 511.69 |
| Baseline T-Helper Lymphocytes Count in Bronchial Tissue | 237.10 cells/mm^2 | 215.05 cells/mm^2 | 200.85 cells/mm^2 |
| Baseline Total T-Lymphocytes Count in Bronchial Tissue | 301.09 cells/mm^2 | 181.50 cells/mm^2 | 153.33 cells/mm^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 40 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 35 Participants | 16 Participants |
| Sex: Female, Male Female | 8 Participants | 21 Participants | 13 Participants |
| Sex: Female, Male Male | 14 Participants | 21 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 20 |
| other Total, other adverse events | 11 / 22 | 14 / 20 |
| serious Total, serious adverse events | 0 / 22 | 1 / 20 |
Outcome results
Primary
Change From Baseline in Eosinophils Cells Count in the Bronchial Submucosa at Week 12
Inflammatory cells i.e. eosinophils were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time frame: Baseline, Week 12
Population: Analysis was performed on pharmacodynamic (PD) population which consisted of all randomized participants who underwent baseline and Week12/end of treatment (EOT) bronchoscopies and have adequate biopsies for analysis at both baseline and EOT. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Eosinophils Cells Count in the Bronchial Submucosa at Week 12 | 5.80 cells/mm^2 |
| Dupilumab | Change From Baseline in Eosinophils Cells Count in the Bronchial Submucosa at Week 12 | -6.04 cells/mm^2 |
Comparison: Analysis was performed using a rank ANCOVA model stratified by ICS dose level and region.p-value: 0.84Rank ANCOVA
Primary
Change From Baseline in Mast Cells Count (Chymase Positive) in the Bronchial Submucosa at Week 12
Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time frame: Baseline, Week 12
Population: Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mast Cells Count (Chymase Positive) in the Bronchial Submucosa at Week 12 | -14.80 cells/mm^2 | Standard Deviation 76.52 |
| Dupilumab | Change From Baseline in Mast Cells Count (Chymase Positive) in the Bronchial Submucosa at Week 12 | 1.76 cells/mm^2 | Standard Deviation 62.41 |
Comparison: Analysis was performed using a linear fixed-effect model with treatment, region and ICS dose level as fixed effects, and the baseline value as continuous covariate.p-value: 0.479590% CI: [-19, 46.78]Linear fixed-effect model
Primary
Change From Baseline in Mast Cells Count (Tryptase Positive) in the Bronchial Submucosa at Week 12
Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time frame: Baseline, Week 12
Population: Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mast Cells Count (Tryptase Positive) in the Bronchial Submucosa at Week 12 | 2.37 cells/mm^2 | Standard Deviation 90.2 |
| Dupilumab | Change From Baseline in Mast Cells Count (Tryptase Positive) in the Bronchial Submucosa at Week 12 | -20.89 cells/mm^2 | Standard Deviation 59.09 |
Comparison: Analysis was performed using a linear fixed-effect model with treatment, region and ICS dose level as fixed effects, and the baseline value as continuous covariate.p-value: 0.449490% CI: [-60.92, 22.97]Linear fixed-effect model
Primary
Change From Baseline in Mucin-Stained Area in the Bronchial Submucosa at Week 12
Mucin was identified by staining with Alcian-blue periodic acid-Schiff and/or immunostaining for MUC5AC and then the mucin-positive area was measured and expressed per square millimeter.
Time frame: Baseline, Week 12
Population: Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mucin-Stained Area in the Bronchial Submucosa at Week 12 | 64.09 cells/mm^2 | Standard Deviation 391.96 |
| Dupilumab | Change From Baseline in Mucin-Stained Area in the Bronchial Submucosa at Week 12 | -142.74 cells/mm^2 | Standard Deviation 477.89 |
Comparison: Analysis was performed using a linear fixed-effect model with treatment, region and ICS dose level as fixed effects, and the baseline value as continuous covariate.p-value: 0.033690% CI: [-414.19, -55.84]Linear fixed-effect model
Primary
Change From Baseline in T-Helper Lymphocytes Count in the Bronchial Submucosa at Week 12
T-helper i.e. CD4 positive lymphocytes were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time frame: Baseline, Week 12
Population: Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in T-Helper Lymphocytes Count in the Bronchial Submucosa at Week 12 | 7.26 cells/mm^2 |
| Dupilumab | Change From Baseline in T-Helper Lymphocytes Count in the Bronchial Submucosa at Week 12 | 62.34 cells/mm^2 |
Comparison: Analysis was performed using a rank ANCOVA model stratified by ICS dose level and region.p-value: 0.7588Rank ANCOVA
Primary
Change From Baseline in T-Lymphocytes Count in the Bronchial Submucosa at Week 12
T-Lymphocytes i.e. CD3 positive cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time frame: Baseline, Week 12
Population: Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in T-Lymphocytes Count in the Bronchial Submucosa at Week 12 | -36.70 cells/mm^2 |
| Dupilumab | Change From Baseline in T-Lymphocytes Count in the Bronchial Submucosa at Week 12 | 34.21 cells/mm^2 |
Comparison: Analysis was performed using a rank ANCOVA model stratified by ICS dose level and region.p-value: 0.6865Rank ANCOVA
Secondary
Average Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 6 Through Week 12
FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/s, and reported in ppb. The average change in FeNO from baseline to Week 6 through Week 12 was calculated as follows: For each participant the change in FeNO from Baseline to Week 6, Week 8, Week 10 and Week 12 was calculated (value at Week X - value at baseline). Subsequently the weekly mean of these 4 change from baseline values was determined (Weeks 6, 8, 10 and 12). Using these weekly mean values the overall arithmetic mean and standard deviation of the average change in FeNO from baseline to Week 6 through Week 12 was calculated.
Time frame: From Baseline to Week 6 through Week 12
Population: Analysis was performed on secondary PD population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 6 Through Week 12 | 3.5 ppb | Standard Deviation 18 |
| Dupilumab | Average Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 6 Through Week 12 | -16.0 ppb | Standard Deviation 21 |
Comparison: Analysis was performed using a Mixed-effect model with Repeated Measures (MMRM) with treatment, treatment-by-visit interaction, region, and ICS dose level as fixed effects, and baseline biomarker-by-visit interaction as fixed covariate, and assuming an unstructured covariance structure separately by treatment group.p-value: 0.000590% CI: [-31.3, -12.8]MMRM
Secondary
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12
FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/second, and reported in ppb.
Time frame: Baseline, Week 12
Population: Analysis was performed on secondary PD population which consisted of all randomized and treated participants. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12 | 3.9 ppb | Standard Deviation 22.8 |
| Dupilumab | Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12 | -15.1 ppb | Standard Deviation 18.3 |
Comparison: Analysis was performed using a Mixed-effect Model with Repeated Measures (MRMM) with treatment, treatment-by-visit interaction, region, and ICS dose level as fixed effects, and baseline biomarker-by-visit interaction as fixed covariate, and assuming an unstructured covariance structure separately by treatment group.p-value: 0.001290% CI: [-32.9, -11.9]MMRM
Secondary
Number of Participants With Antidrug Antibodies (ADA)
Anti-drug antibodies were detected using a validated immunoassay. Incidence of ADA were classified as following: 1) Pre-existing immunoreactivity - an ADA positive response in the assay at baseline with all post treatment ADA results negative or an ADA positive response at baseline with all post treatment ADA responses less than 4-fold over baseline titer levels. 2) Treatment-emergent ADA: an ADA positive response in the assay post first dose, when baseline results were negative or missing. 3) Treatment-boosted ADA: an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive.
Time frame: From Baseline up to 24 weeks
Population: Analysis was performed on ADA population which consisted of all participants with at least one qualified ADA result in the ADA assay following the first dose of the study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Antidrug Antibodies (ADA) | With treatment-emergent ADA | 0 Participants |
| Placebo | Number of Participants With Antidrug Antibodies (ADA) | With pre-existing immunoreactivity | 1 Participants |
| Placebo | Number of Participants With Antidrug Antibodies (ADA) | With treatment-boosted ADA | 0 Participants |
| Dupilumab | Number of Participants With Antidrug Antibodies (ADA) | With pre-existing immunoreactivity | 0 Participants |
| Dupilumab | Number of Participants With Antidrug Antibodies (ADA) | With treatment-emergent ADA | 1 Participants |
| Dupilumab | Number of Participants With Antidrug Antibodies (ADA) | With treatment-boosted ADA | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse event (AE) was defined as any untoward medical occurrence in a participant who received investigational medicinal product (IMP) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during between the first administration of study medication to the end of the 12 week Post-treatment Period. Serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included both serious and non-serious AEs.
Time frame: Baseline up to Week 24
Population: Analysis was performed on safety population which consisted of all participants randomized and exposed to study medication, regardless of the amount of treatment administered.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to death | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any treatment emergent SAE | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to permanent discontinuation | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 17 Participants |
| Dupilumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to permanent discontinuation | 0 Participants |
| Dupilumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to death | 0 Participants |
| Dupilumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 15 Participants |
| Dupilumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any treatment emergent SAE | 1 Participants |
Secondary
Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Serum functional dupilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method.
Time frame: Week 0, Week 2, 6, 8, 12, 18, End of study (Week 24)
Population: Analysis was performed on PK population which consisted of all participants with at least one non-missing and eligible post-baseline dupilumab serum concentration data. Data for this outcome measure was not planned to be analyzed for placebo arm. Here, number analyzed represents number of subjects with available data for specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration | Week 0 | 0.00 ng/mL | Standard Deviation 0 |
| Placebo | Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration | Week 2 | 52675.00 ng/mL | Standard Deviation 23107.55 |
| Placebo | Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration | Week 8 | 61097.95 ng/mL | Standard Deviation 29775.23 |
| Placebo | Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration | Week 6 | 59969.00 ng/mL | Standard Deviation 27422.27 |
| Placebo | Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration | Week 12 | 67387.00 ng/mL | Standard Deviation 32800.44 |
| Placebo | Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration | Week 18 | 20728.17 ng/mL | Standard Deviation 17718.93 |
| Placebo | Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration | Week 24 | 1851.20 ng/mL | Standard Deviation 2796.78 |