| 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. | 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. | Posted | | Median | Inter-Quartile Range | cells/mm^2 | | Baseline, Week 12 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
| | | Title | Denominators | Categories |
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| | | Title | Measurements |
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| - OG0005.80(-9.18 to 33.41)
- OG001-6.04(-174.71 to 19.41)
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| Analysis was performed using a rank ANCOVA model stratified by ICS dose level and region. | Rank ANCOVA | Rank ANCOVA model stratified by ICS dose level and region | 0.8400 | Threshold for significance at 0.05 level | | | | | | | | | | | | | Superiority | | |
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| 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. | Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure. | Posted | | Mean | Standard Deviation | cells/mm^2 | | Baseline, Week 12 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| 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. | Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure. | Posted | | Mean | Standard Deviation | cells/mm^2 | | Baseline, Week 12 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| 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. | Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure. | Posted | | Mean | Standard Deviation | cells/mm^2 | | Baseline, Week 12 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| 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. | Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure. | Posted | | Median | Inter-Quartile Range | cells/mm^2 | | Baseline, Week 12 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| 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. | Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure. | Posted | | Median | Inter-Quartile Range | cells/mm^2 | | Baseline, Week 12 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| 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. | 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. | Posted | | Mean | Standard Deviation | ppb | | Baseline, Week 12 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| 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. | Analysis was performed on secondary PD population. | Posted | | Mean | Standard Deviation | ppb | | From Baseline to Week 6 through Week 12 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| 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. | 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. | Posted | | Count of Participants | | Participants | | From Baseline up to 24 weeks | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| Secondary | Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration | Serum functional dupilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method. | 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. | Posted | | Mean | Standard Deviation | ng/mL | | Week 0, Week 2, 6, 8, 12, 18, End of study (Week 24) | | | | ID | Title | Description |
|---|
| OG000 | 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. |
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| 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. | Analysis was performed on safety population which consisted of all participants randomized and exposed to study medication, regardless of the amount of treatment administered. | Posted | | Count of Participants | | Participants | | Baseline up to Week 24 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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