Trial Outcomes & Findings for Evaluation of Dupilumab's Effects on Airway Inflammation in Patients With Asthma (NCT NCT02573233)
NCT ID: NCT02573233
Last Updated: 2022-04-04
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
42 participants
Primary outcome timeframe
Baseline, Week 12
Results posted on
2022-04-04
Participant Flow
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.
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).
Participant milestones
| Measure |
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 inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
20
|
|
Overall Study
COMPLETED
|
22
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Here, number analyzed = participants with available data at baseline.
Baseline characteristics by cohort
| Measure |
Placebo
n=22 Participants
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.
|
Dupilumab
n=20 Participants
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.
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.0 years
STANDARD_DEVIATION 10.3 • n=22 Participants
|
45.5 years
STANDARD_DEVIATION 10.6 • n=20 Participants
|
43.1 years
STANDARD_DEVIATION 10.6 • n=42 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=22 Participants
|
13 Participants
n=20 Participants
|
21 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=22 Participants
|
7 Participants
n=20 Participants
|
21 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=22 Participants
|
1 Participants
n=20 Participants
|
2 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
21 Participants
n=22 Participants
|
19 Participants
n=20 Participants
|
40 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=22 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=22 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=22 Participants
|
1 Participants
n=20 Participants
|
1 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=22 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=22 Participants
|
3 Participants
n=20 Participants
|
6 Participants
n=42 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=22 Participants
|
16 Participants
n=20 Participants
|
35 Participants
n=42 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=22 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=22 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=42 Participants
|
|
Baseline Eosinophils Count in Bronchial Tissue
|
12.97 cells/mm^2
n=21 Participants • Here, number analyzed = participants with available data at baseline.
|
34.96 cells/mm^2
n=19 Participants • Here, number analyzed = participants with available data at baseline.
|
20.73 cells/mm^2
n=40 Participants • Here, number analyzed = participants with available data at baseline.
|
|
Baseline Mucin-Stained Area in The Bronchial Tissue Specimen
|
561.12 cells/mm^2
STANDARD_DEVIATION 289.00 • n=22 Participants • Here, number analyzed = participants with available data at baseline.
|
520.57 cells/mm^2
STANDARD_DEVIATION 511.69 • n=19 Participants • Here, number analyzed = participants with available data at baseline.
|
542.33 cells/mm^2
STANDARD_DEVIATION 402.61 • n=41 Participants • Here, number analyzed = participants with available data at baseline.
|
|
Baseline Mast Cells Count (Chymase Positive) in Bronchial Tissue
|
74.36 cells/mm^2
STANDARD_DEVIATION 58.63 • n=22 Participants
|
79.17 cells/mm^2
STANDARD_DEVIATION 68.07 • n=20 Participants
|
76.59 cells/mm^2
STANDARD_DEVIATION 62.42 • n=42 Participants
|
|
Baseline Mast Cells Count (Tryptase Positive) in Bronchial Tissue
|
80.10 cells/mm^2
STANDARD_DEVIATION 64.92 • n=22 Participants • Here, number analyzed = participants with available data at baseline.
|
105.53 cells/mm^2
STANDARD_DEVIATION 104.68 • n=19 Participants • Here, number analyzed = participants with available data at baseline.
|
91.88 cells/mm^2
STANDARD_DEVIATION 85.49 • n=41 Participants • Here, number analyzed = participants with available data at baseline.
|
|
Baseline Total T-Lymphocytes Count in Bronchial Tissue
|
301.09 cells/mm^2
n=22 Participants • Here, number analyzed = participants with available data at baseline.
|
153.33 cells/mm^2
n=19 Participants • Here, number analyzed = participants with available data at baseline.
|
181.50 cells/mm^2
n=41 Participants • Here, number analyzed = participants with available data at baseline.
|
|
Baseline T-Helper Lymphocytes Count in Bronchial Tissue
|
237.10 cells/mm^2
n=22 Participants • Here, number analyzed = participants with available data at baseline.
|
200.85 cells/mm^2
n=19 Participants • Here, number analyzed = participants with available data at baseline.
|
215.05 cells/mm^2
n=41 Participants • Here, number analyzed = participants with available data at baseline.
|
|
Baseline Fractional exhaled nitric oxide (FeNO)
|
41.2 parts per billion (ppb)
STANDARD_DEVIATION 31.5 • n=22 Participants
|
36.4 parts per billion (ppb)
STANDARD_DEVIATION 22.8 • n=20 Participants
|
38.9 parts per billion (ppb)
STANDARD_DEVIATION 27.5 • n=42 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=20 Participants
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.
|
Dupilumab
n=17 Participants
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.
|
|---|---|---|
|
Change From Baseline in Eosinophils Cells Count in the Bronchial Submucosa at Week 12
|
5.80 cells/mm^2
Interval -9.18 to 33.41
|
-6.04 cells/mm^2
Interval -174.71 to 19.41
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
Placebo
n=20 Participants
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.
|
Dupilumab
n=16 Participants
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.
|
|---|---|---|
|
Change From Baseline in Mucin-Stained Area in the Bronchial Submucosa at Week 12
|
64.09 cells/mm^2
Standard Deviation 391.96
|
-142.74 cells/mm^2
Standard Deviation 477.89
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
Placebo
n=20 Participants
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.
|
Dupilumab
n=17 Participants
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.
|
|---|---|---|
|
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
|
1.76 cells/mm^2
Standard Deviation 62.41
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
Placebo
n=21 Participants
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.
|
Dupilumab
n=17 Participants
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.
|
|---|---|---|
|
Change From Baseline in Mast Cells Count (Tryptase Positive) in the Bronchial Submucosa at Week 12
|
2.37 cells/mm^2
Standard Deviation 90.20
|
-20.89 cells/mm^2
Standard Deviation 59.09
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
Placebo
n=20 Participants
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.
|
Dupilumab
n=16 Participants
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.
|
|---|---|---|
|
Change From Baseline in T-Lymphocytes Count in the Bronchial Submucosa at Week 12
|
-36.70 cells/mm^2
Interval -200.25 to 267.51
|
34.21 cells/mm^2
Interval -95.08 to 232.99
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Analysis was performed on PD population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
Placebo
n=20 Participants
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.
|
Dupilumab
n=16 Participants
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.
|
|---|---|---|
|
Change From Baseline in T-Helper Lymphocytes Count in the Bronchial Submucosa at Week 12
|
7.26 cells/mm^2
Interval -179.43 to 224.96
|
62.34 cells/mm^2
Interval -100.62 to 159.09
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=21 Participants
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.
|
Dupilumab
n=18 Participants
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.
|
|---|---|---|
|
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12
|
3.9 ppb
Standard Deviation 22.8
|
-15.1 ppb
Standard Deviation 18.3
|
SECONDARY outcome
Timeframe: From Baseline to Week 6 through Week 12Population: Analysis was performed on secondary PD population.
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.
Outcome measures
| Measure |
Placebo
n=22 Participants
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.
|
Dupilumab
n=20 Participants
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.
|
|---|---|---|
|
Average Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 6 Through Week 12
|
3.5 ppb
Standard Deviation 18.0
|
-16.0 ppb
Standard Deviation 21.0
|
SECONDARY outcome
Timeframe: From Baseline up to 24 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=21 Participants
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.
|
Dupilumab
n=19 Participants
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.
|
|---|---|---|
|
Number of Participants With Antidrug Antibodies (ADA)
With pre-existing immunoreactivity
|
1 Participants
|
0 Participants
|
|
Number of Participants With Antidrug Antibodies (ADA)
With treatment-emergent ADA
|
0 Participants
|
1 Participants
|
|
Number of Participants With Antidrug Antibodies (ADA)
With treatment-boosted ADA
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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.
Serum functional dupilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method.
Outcome measures
| Measure |
Placebo
n=20 Participants
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.
|
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.
|
|---|---|---|
|
Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Week 0
|
0.00 ng/mL
Standard Deviation 0.00
|
—
|
|
Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Week 2
|
52675.00 ng/mL
Standard Deviation 23107.55
|
—
|
|
Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Week 6
|
59969.00 ng/mL
Standard Deviation 27422.27
|
—
|
|
Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Week 8
|
61097.95 ng/mL
Standard Deviation 29775.23
|
—
|
|
Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Week 12
|
67387.00 ng/mL
Standard Deviation 32800.44
|
—
|
|
Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Week 18
|
20728.17 ng/mL
Standard Deviation 17718.93
|
—
|
|
Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Week 24
|
1851.20 ng/mL
Standard Deviation 2796.78
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: Analysis was performed on safety population which consisted of all participants randomized and exposed to study medication, regardless of the amount of treatment administered.
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.
Outcome measures
| Measure |
Placebo
n=22 Participants
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.
|
Dupilumab
n=20 Participants
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.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Any TEAE
|
17 Participants
|
15 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Any treatment emergent SAE
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Any TEAE leading to death
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Any TEAE leading to permanent discontinuation
|
0 Participants
|
0 Participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Dupilumab
Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=22 participants at risk
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.
|
Dupilumab
n=20 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/22 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
5.0%
1/20 • Number of events 1 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
Other adverse events
| Measure |
Placebo
n=22 participants at risk
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.
|
Dupilumab
n=20 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
4.5%
1/22 • Number of events 1 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
15.0%
3/20 • Number of events 3 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/22 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
10.0%
2/20 • Number of events 2 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
General disorders
Injection Site Erythema
|
9.1%
2/22 • Number of events 8 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
15.0%
3/20 • Number of events 8 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
General disorders
Injection Site Inflammation
|
9.1%
2/22 • Number of events 3 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
5.0%
1/20 • Number of events 3 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
General disorders
Injection Site Pruritus
|
4.5%
1/22 • Number of events 1 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
10.0%
2/20 • Number of events 3 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Infections and infestations
Nasopharyngitis
|
18.2%
4/22 • Number of events 6 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
10.0%
2/20 • Number of events 2 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
4.5%
1/22 • Number of events 1 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
15.0%
3/20 • Number of events 3 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Injury, poisoning and procedural complications
Accidental Overdose
|
4.5%
1/22 • Number of events 1 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
10.0%
2/20 • Number of events 3 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Injury, poisoning and procedural complications
Road Traffic Accident
|
0.00%
0/22 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
10.0%
2/20 • Number of events 2 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/22 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
15.0%
3/20 • Number of events 3 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Nervous system disorders
Headache
|
13.6%
3/22 • Number of events 9 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
25.0%
5/20 • Number of events 11 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
4.5%
1/22 • Number of events 1 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
10.0%
2/20 • Number of events 2 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.1%
2/22 • Number of events 2 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
5.0%
1/20 • Number of events 1 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
9.1%
2/22 • Number of events 2 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
0.00%
0/20 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
|
Vascular disorders
Hypertension
|
9.1%
2/22 • Number of events 3 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
5.0%
1/20 • Number of events 1 • All AEs were collected from signature of the informed consent form up to the end of study (i.e. up to the end of Post-treatment period [Week 24]) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during 'treatment-emergent period' (from first dose of investigational product injection up to the end of Post-treatment period \[Week 24\]). Analysis was performed on safety population.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
- Publication restrictions are in place
Restriction type: OTHER