Clinical Trial Results:
Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Dupilumab on Airway Inflammation Through Assessments of Lung Function, Mucus Plugging and Other Lung Imaging Parameters in Patients with Asthma
Summary
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EudraCT number |
2019-004647-74 |
Trial protocol |
GB DK SE PT ES BG FR IT RO |
Global end of trial date |
21 Aug 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Jul 2024
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First version publication date |
28 Jul 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LPS15834
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04400318 | ||
WHO universal trial number (UTN) |
U1111-1238-4679 | ||
Sponsors
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Sponsor organisation name |
Sanofi SAG
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Sponsor organisation address |
54-56 Rue la Boétie, Paris, France, 75008
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Sep 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Aug 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the effect of dupilumab on lung inflammation and related changes in airway volumes detectable by functional respiratory imaging.
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Protection of trial subjects |
Participants were fully informed of all pertinent aspects of clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the participant and considering the local culture. During the course of the trail, participants were provided with individual participant cards indicating the nature of the trial the participant is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Jun 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Bulgaria: 36
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Country: Number of subjects enrolled |
Denmark: 7
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Italy: 1
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Country: Number of subjects enrolled |
Portugal: 1
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Country: Number of subjects enrolled |
Romania: 11
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Country: Number of subjects enrolled |
Saudi Arabia: 4
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Country: Number of subjects enrolled |
Spain: 7
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Country: Number of subjects enrolled |
Taiwan: 5
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Country: Number of subjects enrolled |
Ukraine: 23
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
United States: 11
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Worldwide total number of subjects |
109
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EEA total number of subjects |
64
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
96
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From 65 to 84 years |
13
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 317 participants were screened from 20 Jun 2020 to 06 Jan 2023 at 72 study sites in 14 countries of which 208 participants were screen failures. Screen failures were mainly due to not meeting the eligibility criteria. | |||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 109 participants were randomized in a ratio of 2:1 to receive dupilumab 300 milligrams (mg) or matching placebo every 2 weeks (Q2W) for 24 weeks. Randomization was stratified by inhaled corticosteroids (ICS) dose level (medium/high no less than 40% in ‘high ICS’ stratum) and region (Eastern Europe/Rest of the World [ROW]). | |||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Dupilumab 300 mg Q2W | |||||||||||||||||||||
Arm description |
Participants received a loading dose of dupilumab 600 mg as 2 subcutaneous (SC) injections on Day 1, followed by a single dupilumab 300 mg SC injection Q2W for 24 weeks along with a stable dose of medium to high ICS dose in combination with a second controller medication +/- a third controller. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Dupilumab
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Investigational medicinal product code |
SAR231893
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Dupilumab was supplied as a 150 milligram per milliliter (mg/mL) solution in prefilled glass syringe to deliver 300 mg in a 2 mL injection. SC injection sites were alternated between the upper thighs, 4 quadrants of the abdomen or the upper arms, so that the same site was not injected twice during consecutive administrations.
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
Participants received placebo matched to dupilumab as 2 x 2 milliliter (mL) SC injections on Day 1, followed by a single SC injection Q2W for 24 weeks along with a stable dose of medium to high ICS dose in combination with a second controller medication +/- a third controller. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Matching placebo was supplied as an identical formulation to the active formulation without dupilumab, in a prefilled syringe to deliver placebo in a 2 mL injection. SC injection sites were alternated between the upper thighs, 4 quadrants of the abdomen or the upper arms, so that the same site was not injected twice during consecutive administrations.
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Baseline characteristics reporting groups
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Reporting group title |
Dupilumab 300 mg Q2W
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Reporting group description |
Participants received a loading dose of dupilumab 600 mg as 2 subcutaneous (SC) injections on Day 1, followed by a single dupilumab 300 mg SC injection Q2W for 24 weeks along with a stable dose of medium to high ICS dose in combination with a second controller medication +/- a third controller. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo matched to dupilumab as 2 x 2 milliliter (mL) SC injections on Day 1, followed by a single SC injection Q2W for 24 weeks along with a stable dose of medium to high ICS dose in combination with a second controller medication +/- a third controller. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Dupilumab 300 mg Q2W
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Reporting group description |
Participants received a loading dose of dupilumab 600 mg as 2 subcutaneous (SC) injections on Day 1, followed by a single dupilumab 300 mg SC injection Q2W for 24 weeks along with a stable dose of medium to high ICS dose in combination with a second controller medication +/- a third controller. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo matched to dupilumab as 2 x 2 milliliter (mL) SC injections on Day 1, followed by a single SC injection Q2W for 24 weeks along with a stable dose of medium to high ICS dose in combination with a second controller medication +/- a third controller. |
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End point title |
Percentage of Participants who Achieved Fractional Exhaled Nitric Oxide (FeNO) Less Than (<) 25 Parts Per Billion (ppb) at Week 24 | ||||||||||||
End point description |
FeNO was analyzed using a NIOX instrument using a flow rate of 50 milliliters per second (mL/s). This assessment was conducted prior to spirometry and following a fast of greater than or equal to (≥1) hour. The test was performed after a wash out period of bronchodilators. The ITT analysis set consisted of randomized participants (participants with a study intervention kit number allocated and recorded in the IVRS/IWRS database, regardless of whether the study intervention kit was used or not).
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End point type |
Primary
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End point timeframe |
Week 24
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Statistical analysis title |
Dupilumab 300 mg Q2W versus Placebo | ||||||||||||
Statistical analysis description |
Odds Ratio, 95% confidence interval (CI) of the odds ratio and p-value between the dupilumab and placebo group based on the Cochran-Mantel-Haenszel (CMH) test adjusted by ICS dose level (medium/high) and region (Eastern Europe/ROW).
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Comparison groups |
Dupilumab 300 mg Q2W v Placebo
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Number of subjects included in analysis |
109
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
9.81
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
3.13 | ||||||||||||
upper limit |
30.82 |
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End point title |
Percent Change From Baseline to Week 24 in Untrimmed Distal Specific Airway Volumes ([s]iVaw) at Total Lung Capacity (TLC) | ||||||||||||
End point description |
Specific airway volume [(s)iVaw] is the change of volume of the airways (in mL), taking into account the lung volume changes (in liter [L]) as well. It corresponds to the ratio between the airway volume (iVaw) and the lobar volume. This way the airway volumes are normalized across participants and become specific. Untrimmed distal [s]iVaw at TLC was assessed based on 3-dimensional (D) rendering of high-resolution computed tomography (HRCT) scans. Baseline was defined as the last available valid (non-missing) value up to and including the day of first dose of investigational medicinal product (IMP). The ITT analysis set consisted of randomized participants (participants with a study intervention kit number allocated and recorded in the IVRS/IWRS database, regardless of whether the study intervention kit was used or not). Only participants with data collected at Week 24 are reported.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1) to Week 24
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Statistical analysis title |
Dupilumab 300 mg Q2W versus Placebo | ||||||||||||
Statistical analysis description |
The mixed model for repeated measures (MMRM) included study intervention, baseline value, region, ICS dose level, visits, study intervention by visit interaction, and baseline by visit interaction terms all as fixed effects. Region, ICS, study intervention and visits were considered as categorical parameters.
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Comparison groups |
Dupilumab 300 mg Q2W v Placebo
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Number of subjects included in analysis |
102
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.138 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Least square mean difference | ||||||||||||
Point estimate |
21.76
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-7.73 | ||||||||||||
upper limit |
51.25 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
14.022
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End point title |
Change From Baseline to Week 24 in Global Lung Mucus Score (University of California, San Francisco [UCSF] Mucus Scoring) | ||||||||||||
End point description |
The mucus scoring system was derived, with very minor differences, from UCSF mucus score. The mucus score was calculated by counting the number of bronchopulmonary segments which contained 1 or more mucus plug, up to a maximum score of 18 corresponding to the 18 bronchopulmonary segments present in most people. In this system, a mucus plug is defined as a complete occlusion of the airway visible at TLC. Each bronchopulmonary segment is given a score of 1 (mucus plug[s] present) or 0 (mucus plug[s] absent). The segment scores of each lobe are summed to generate a total mucus score for both lungs, yielding a mucus score ranging from 0-18. Higher scores indicate worse outcome. Baseline was defined as the last available valid (non-missing) value up to and including the date of first dose of IMP. Results are based on the ITT analysis set. Only participants with data collected at Week 24 are reported.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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Statistical analysis title |
Dupilumab 300 mg Q2W versus Placebo | ||||||||||||
Statistical analysis description |
MMRM model included study intervention (dupilumab, placebo), baseline value of global lung UCSF mucus scoring, region (Eastern Europe/ROW), ICS dose level (medium/high), visit (up to Week 24), study intervention-by-visit interaction and baseline-by-visit interaction as covariates.
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Comparison groups |
Dupilumab 300 mg Q2W v Placebo
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Number of subjects included in analysis |
102
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Least square mean difference | ||||||||||||
Point estimate |
-4.92
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-6.5 | ||||||||||||
upper limit |
-3.34 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.798
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Notes [1] - A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the endpoint is reported and continued when previous endpoint was statistically significant at two-sided 0.05. Only 2 endpoints measures (#4 and #5) were included in this procedure. |
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End point title |
Percent Change From Baseline to Week 24 in Trimmed Distal Specific Airway Resistance ([s]iRaw) at TLC | ||||||||||||
End point description |
iRaw is defined as the total pressure drop over an airway, divided by the flow rate through that airway. The specific airway resistance (s)iRaw is derived from iRaw by multiplying the airway resistance with the lobar volume. This way the airway resistances are normalized across participants and become specific. Trimmed distal ([s]iRaw) at TLC was assessed using HRCT scan. Baseline was defined as the last available valid (non-missing) value up to and including the day of first dose of IMP. The ITT analysis set consisted of randomized participants (participants with a study intervention kit number allocated and recorded in the IVRS/IWRS database, regardless of whether the study intervention kit was used or not). Only participants with data collected at Week 24 are reported.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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Statistical analysis title |
Dupilumab 300 mg Q2W versus Placebo | ||||||||||||
Statistical analysis description |
MMRM model included study intervention (dupilumab, placebo), baseline value of trimmed distal [s]iRaw at TLC, region (Eastern Europe/ROW), ICS dose level (medium/high), visit (up to Week 24), study intervention-by-visit interaction, and baseline-by-visit interaction as covariates.
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Comparison groups |
Dupilumab 300 mg Q2W v Placebo
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Number of subjects included in analysis |
102
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Analysis specification |
Pre-specified
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Analysis type |
superiority [2] | ||||||||||||
P-value |
= 0.18 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Least square mean difference | ||||||||||||
Point estimate |
-53.45
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-132.09 | ||||||||||||
upper limit |
25.19 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
39.562
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Notes [2] - A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the endpoint is reported and continued when previous endpoint was statistically significant at two-sided 0.05. Only 2 secondary endpoints (#4 and #5) were included in this procedure. |
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End point title |
Percent Change From Baseline to Week 24 in Untrimmed Distal Specific Airway Volumes ([s]iVaw) at Functional Residual Capacity (FRC) | ||||||||||||
End point description |
(s)iVaw is the change of volume of the airways (mL), taking into account the lung volume changes (in L) as well. It corresponds to the ratio between the airway volume (iVaw) and the lobar volume. Untrimmed distal [s]iVaw at FRC was assessed based on 3D rendering of HRCT scans. Baseline was defined as the last available valid (non-missing) value up to and including the day of first dose of IMP. The ITT analysis set consisted of randomized participants (participants with a study intervention kit number allocated and recorded in the IVRS/IWRS database, regardless of whether the study intervention kit was used or not). Only participants with data collected at Week 24 are reported.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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No statistical analyses for this end point |
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End point title |
Percent Change From Baseline to Week 24 in Trimmed Distal Specific Airway Resistance ([s]iRaw) at FRC | ||||||||||||
End point description |
iRaw is defined as the total pressure drop over an airway, divided by the flow rate through that airway. The specific airway resistance (s)iRaw is derived from iRaw by multiplying the airway resistance with the lobar volume. This way, the airway resistances are normalized across participants and become specific. Trimmed distal [s]iRaw at FRC was assessed using HRCT scan. Baseline was defined as the last available valid (non-missing) value up to and including the day of the first dose of IMP. The ITT analysis set consisted of randomized participants (participants with a study intervention kit number allocated and recorded in the IVRS/IWRS database, regardless of whether the study intervention kit was used or not). Only participants with data collected at Week 24 are reported.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Week 24 in HRCT-Based Internal Airflow Distribution (IAD) for Each Lung Zone | ||||||||||||||||||
End point description |
The IAD was assessed in the upper and lower lung using HRCT scan. By segmenting the lobes at FRC and TLC for each participant, the participant-specific airflow distribution can be established by assessing lobar and volume expansion. Baseline was defined as the last available valid (non-missing) value up to and including the date of the first dose of IMP. The ITT analysis set consisted of randomized participants (participants with a study intervention kit number allocated and recorded in the IVRS/IWRS database, regardless of whether the study intervention kit was used or not). Only participants with data collected at Week 24 are reported.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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No statistical analyses for this end point |
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End point title |
Percent Change From Baseline to Week 24 in Global Lung Lobar Volumes (iVlobes) at TLC | ||||||||||||
End point description |
The lung volume was determined from the HRCT scan at TLC, by identifying and grouping the voxels that represent the air in the lungs. The total lung volume along with the volume of each lobe individually was determined which allowed to pick up substantial regional physiological changes of the airways and the lobe volumes. Baseline was defined as the last available valid (non-missing) value up to and including the day of first dose of IMP. The ITT analysis set consisted of randomized participants (participants with a study intervention kit number allocated and recorded in the IVRS/IWRS database, regardless of whether the study intervention kit was used or not). Only participants with data collected at Week 24 are reported.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Week 24 in Image-Based Ventilation/Perfusion (iV/Q) at TLC for Each Lung Zone | ||||||||||||||||||
End point description |
Blood vessel density can be considered a surrogate for perfusion, hence image-based perfusion (IQ) is calculated by blood vessel density at TLC multiplied by image-based volume at TLC. Image-based ventilation (IV) is calculated by the imaged volume at TLC subtracted from the image-based volume at FRC. The ventilation/perfusion ratio IV/Q is then the ratio IV/IQ. The iV/Q was assessed in the upper and lower lung using HRCT scan at TLC. Baseline was defined as the last available valid (non-missing) value up to and including the day of the first dose of IMP. The ITT analysis set consisted of randomized participants (participants with a study intervention kit number allocated and recorded in the IVRS/IWRS database, regardless of whether the study intervention kit was used or not). Only participants with data collected at Week 24 are reported.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Week 24 in FeNO | ||||||||||||
End point description |
FeNO was analyzed using a NIOX instrument using a flow rate of 50 mL/s. This assessment was conducted prior to spirometry and following a fast of ≥1 hour. The test was performed after a wash out period of bronchodilators. Baseline was defined as the last available valid (non-missing) value up to and including the day of the first dose of IMP. The ITT analysis set consisted of randomized participants (participants with a study intervention kit number allocated and recorded in the IVRS/IWRS database, regardless of whether the study intervention kit was used or not).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Week 24 in Pre-Bronchodilator and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | ||||||||||||||||||
End point description |
FEV1 was the volume of air exhaled in the first second of a forced expiration. Lung function parameters: pre- and post-bronchodilator FEV1 were measured by spirometry before IMP administration. Spirometry was performed after a wash out period of bronchodilators. Post-BD FEV1 was measured within 30 minutes after short-acting beta-2 agonists (2 to up to 4 puffs of albuterol/salbutamol) administration. Baseline was defined as the last available valid (non-missing) value up to and including the date of the first dose of IMP. The ITT analysis set consisted of randomized participants (participants with a study intervention kit number allocated and recorded in the IVRS/IWRS database, regardless of whether the study intervention kit was used or not).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Week 24 in 7 Item Asthma Control Questionnaire (ACQ-7) | ||||||||||||
End point description |
The ACQ-7 comprises of 7 items: first 5 items assess most common asthma symptoms:1.frequency in past week awoken by asthma during night;2.severity of asthma symptoms in morning; 3.limitation of daily activities due to asthma; 4.shortness of breath due to asthma;5.wheeze; plus questions 6.short-acting bronchodilator use; and 7.FEV1 (pre-bronchodilator use, % and % predicted use).Participants are asked to recall how their asthma has been during previous week,to respond to symptom questions on a 7-point scale (0=no impairment,6=maximum impairment).Clinic staff scores the FEV1% predicted on a 7-point scale.A global score is calculated:questions are equally weighted;overall ACQ-7 score is mean of 7 questions, between 0 (totally controlled) and 6 (severely uncontrolled).Higher score indicates lower asthma control.Baseline=last available valid (non-missing) value up to and including day of first dose of IMP. ITT analysis set.Only participants with data collected at Week 24 are reported.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 24
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No statistical analyses for this end point |
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End point title |
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events of Special Interest (AESIs) | ||||||||||||||||||
End point description |
AE:any untoward medical occurrence in participant/clinical study participant, temporally associated with use of study intervention, whether or not considered related to study intervention. TEAEs:AEs that developed or worsened or became serious during TEAE period, defined as time from first administration of IMP (Day 1) to last administration of IMP+98 days and up to end of study follow-up. Serious adverse events(SAE):AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, was medically important event. AESI:AE (serious or nonserious) of scientific and medical concern specific to Sponsor’s product or program, for which ongoing monitoring and immediate notification by Investigator to Sponsor is required. The safety analysis set included all randomized participants who received at least 1 injection of IMP.
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End point type |
Secondary
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End point timeframe |
From first dose of study drug (Day 1) up to end of study (up to 36 weeks)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of study drug (Day 1) up to end of study (up to 36 weeks)
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Adverse event reporting additional description |
Analysis was performed on safety analysis set.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
Dupilumab 300 mg Q2W
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Reporting group description |
Participants received a loading dose of dupilumab 600 mg as 2 SC injections on Day 1, followed by a single dupilumab 300 mg SC injection Q2W for 24 weeks along with a stable dose of medium to high ICS dose in combination with a second controller medication +/- a third controller. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo matched to dupilumab as 2 x 2 mL SC injections on Day 1, followed by a single SC injection Q2W for 24 weeks along with a stable dose of medium to high ICS dose in combination with a second controller medication +/- a third controller. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Mar 2020 |
The main reason for this amendment was to meet requirements for Regulatory Agency. |
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15 Mar 2021 |
The main reasons for this amendment were to introduce some clarifications in the eligibility criteria, to decrease the participant burden and to allow more flexibility for some of the study procedures (e.g., FeNO assessment, complete clinical examination, the sequence of the study procedures). The safety reporting (AESI) were aligned with the updated Investigator’s brochure and contingency measures were incorporated in case of a regional or national emergency. The stratification factor related to regions was changed to Eastern Europe/ROW. In total, no more than 40% participants should be in "Eastern Europe" strata. |
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13 Apr 2023 |
The main reason for this amendment was evolving interest to evaluate FeNO as an airway inflammatory biomarker related to structural lung changes. Therefore, the primary endpoint FEV1 was proposed to be replaced with the secondary endpoint of FeNO, leading to an overall reduction in sample size. Objectives and
Endpoints section was updated. Updates were made to the sample size calculation and hypotheses reflecting the change to the primary endpoint. The efficacy analyses were updated based on changes to the endpoints. Minor grammatical, editorial, and/or administrative changes were made. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |