Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Severe Steroid Dependent Asthma
Summary
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EudraCT number |
2015-001573-40 |
Trial protocol |
NL ES BE PL HU IT |
Global end of trial date |
13 Nov 2017
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Results information
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Results version number |
v2(current) |
This version publication date |
03 Nov 2019
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First version publication date |
28 May 2018
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Other versions |
v1 |
Version creation reason |
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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 |
EFC13691
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02528214 | ||
WHO universal trial number (UTN) |
U1111-1170-7152 | ||
Other trial identifiers |
Study Name: LIBERTY ASTHMA VENTURE | ||
Sponsors
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Sponsor organisation name |
Sanofi aventis recherche & développement
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Sponsor organisation address |
1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
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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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Dec 2017
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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 |
13 Nov 2017
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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 evaluate the efficacy of dupilumab, compared with placebo, for reducing the use of maintenance oral corticosteroids (OCS) in subjects with severe steroid-dependent asthma.
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Protection of trial subjects |
Paediatric Subjects: The study was conducted by investigators experienced in the treatment of paediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anaesthesia may have been used to minimize distress and discomfort. Adult Subjects: Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. The following applies to both Paediatric and Adult Subjects: During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject 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 |
Oral corticosteroids (OCS [(prednisone or prednisolone]) therapy and stable high dose of inhaled corticosteroid (ICS) in combination with a second or third controller medication for at least 1 month prior to screening and continued throughout the study. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Oct 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Netherlands: 5
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Country: Number of subjects enrolled |
Poland: 41
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Country: Number of subjects enrolled |
Romania: 12
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Country: Number of subjects enrolled |
Spain: 10
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Country: Number of subjects enrolled |
Belgium: 5
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Country: Number of subjects enrolled |
Hungary: 7
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Country: Number of subjects enrolled |
Argentina: 17
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Country: Number of subjects enrolled |
Brazil: 6
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Country: Number of subjects enrolled |
Canada: 12
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Country: Number of subjects enrolled |
Chile: 17
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Country: Number of subjects enrolled |
Israel: 9
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Country: Number of subjects enrolled |
Italy: 12
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Country: Number of subjects enrolled |
Mexico: 17
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Country: Number of subjects enrolled |
Russian Federation: 12
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Country: Number of subjects enrolled |
Ukraine: 19
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Country: Number of subjects enrolled |
United States: 9
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Worldwide total number of subjects |
210
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EEA total number of subjects |
92
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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) |
3
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Adults (18-64 years) |
179
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From 65 to 84 years |
28
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 68 centers in 17 countries. A total of 390 subjects were screened between October 2015 & April 2017, of which 210 were randomized & treated. 180 subjects were screen failures mainly due to exclusion criteria met & inclusion criteria not met. Assignment was done by Interactive Voice/Web Response System(IVRS/IWRS). | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
The screening period included an OCS optimization phase(up to 10 weeks)where subjects using OCS other than prednisone/prednisolone switched to these OCS. At the end of period, subjects were randomized in 1:1 ratio for dupilumab & placebo. Randomization was stratified by optimized OCS dose(=<10mg/day & >10mg/day) at randomization visit & by country. | ||||||||||||||||||||||||
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 |
Investigator, Carer, Subject | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo q2w | ||||||||||||||||||||||||
Arm description |
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until week 20. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo (for Dupilumab)
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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 |
Subcutaneous injection (2 ml) in the abdomen or upper thigh or upper arm.
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Arm title
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Dupilumab 300 mg q2w | ||||||||||||||||||||||||
Arm description |
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until week 20. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Dupilumab
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Investigational medicinal product code |
SAR231893, REGN668
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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 |
Subcutaneous injection (300 mg/2 ml) in the abdomen, upper thigh or upper arm.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo q2w
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Reporting group description |
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until week 20. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Dupilumab 300 mg q2w
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Reporting group description |
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until week 20. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo q2w
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Reporting group description |
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until week 20. | ||
Reporting group title |
Dupilumab 300 mg q2w
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Reporting group description |
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until week 20. |
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End point title |
Percentage Reduction From Baseline in Oral Corticosteroids (OCS) Dose at Week 24 While Maintaining Asthma Control | ||||||||||||
End point description |
Percentage reduction of OCS dose was calculated as (optimized OCS dose [mg/day] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100. Result is presented as Least Squares Mean (Standard Error) percentage reduction from baseline derived from ANCOVA model with missing data multiply imputed. Analysis was performed on intent-to- treat (ITT) population which included randomized population analyzed according to the treatment group allocated by randomization regardless of whether the treatment kit was used or not.
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End point type |
Primary
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End point timeframe |
Baseline, Week 24
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Statistical analysis title |
Dupilumab vs. Placebo | ||||||||||||
Statistical analysis description |
The endpoint was analyzed using analysis of covariance (ANCOVA) model which included percentage reduction of OCS dose at Week 24 as the response variable, and treatment group, baseline eosinophil level, optimized OCS dose at baseline, region as covariates. Missing data was imputed using a pattern mixture model by multiple imputation approach.
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Comparison groups |
Dupilumab 300 mg q2w v Placebo q2w
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Number of subjects included in analysis |
210
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
< 0.0001 [2] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Least square (LS) mean difference | ||||||||||||
Point estimate |
28.24
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
15.81 | ||||||||||||
upper limit |
40.67 | ||||||||||||
Notes [1] - A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the endpoints are reported and continued when previous endpoint was statistically significant at two-sided 0.05. Only the primary and the first 4 secondary endpoints were included in the procedure. [2] - Threshold for significance at two-sided 0.05 level. LS mean difference represents reduction difference i.e. dupilumab - placebo. |
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End point title |
Supplementary Presentation of Primary Endpoint Data: Median Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control [3] | ||||||||||||
End point description |
The Primary Endpoint (Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control) is summarized above, as LS Mean (SE). Table below provides a supplementary presentation of the Primary Endpoint data; result is presented as median (inter-quartile range). Percentage reduction of OCS dose was calculated as (optimized OCS dose [mg/day] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100. Analysis population included ITT patients with available data.
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End point type |
Primary
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End point timeframe |
Baseline, Week 24
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The Primary Endpoint (Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control) is summarized separately above, as LS Mean (SE), with accompanying ANCOVA statistical analysis. This supplementary presentation of the Primary Endpoint data as median (inter-quartile range) has no separate statistical analysis. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Achieving >= 50% Reduction in Oral Corticosteroids dose at Week 24 While Maintaining Asthma Control | ||||||||||||
End point description |
Subjects were classified according to the binary status of whether or not the 50% OCS dose reduction criterion was achieved at week 24. Analysis was performed on ITT population.
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End point type |
Secondary
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End point timeframe |
Week 24
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Statistical analysis title |
Dupilumab 300 mg q2w vs. Placebo q2w | ||||||||||||
Statistical analysis description |
The endpoint was analyzed using a logistic regression model. The model included the binary status of whether or not a subject achieved the 50% OCS dose reduction criterion as the response variable, and treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed by using a pattern mixture model by multiple imputation approach.
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Comparison groups |
Dupilumab 300 mg q2w v Placebo q2w
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Number of subjects included in analysis |
210
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Analysis specification |
Pre-specified
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Analysis type |
superiority [4] | ||||||||||||
P-value |
< 0.0001 [5] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
3.98
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
2.06 | ||||||||||||
upper limit |
7.67 | ||||||||||||
Notes [4] - Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant). [5] - Threshold for significance at 0.05. |
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End point title |
Percentage of Subjects Achieving a Reduction in Oral Corticosteroids dose to <5 mg/day at Week 24 While Maintaining Asthma Control | ||||||||||||
End point description |
Subjects were classified according to the binary status of whether or not the reduction of OCS dose to <5 mg/day was achieved at week 24. Analysis was performed on ITT population.
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End point type |
Secondary
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End point timeframe |
Week 24
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Statistical analysis title |
Dupilumab 300 mg q2w vs. Placebo q2w | ||||||||||||
Statistical analysis description |
The endpoint was analyzed using a logistic regression model. The model included the binary status of whether or not a subject achieved a reduction of OCS dose to <5 mg/day at Week 24 as the response variable, treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed by using a pattern mixture model by multiple imputation approach.
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Comparison groups |
Dupilumab 300 mg q2w v Placebo q2w
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Number of subjects included in analysis |
210
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Analysis specification |
Pre-specified
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Analysis type |
superiority [6] | ||||||||||||
P-value |
< 0.0001 [7] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
4.48
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
2.39 | ||||||||||||
upper limit |
8.39 | ||||||||||||
Notes [6] - Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant). [7] - Threshold for significance at 0.05. |
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End point title |
Percentage of Subjects Achieving Maximum Possible Reduction in Oral Corticosteroids Dose Per Protocol at Week 24 While Maintaining Asthma Control | ||||||||||||
End point description |
For all subjects except those with baseline OCS dose at 35 mg/day, the maximum possible reduction corresponds to reduction to 0 mg/day (no longer requiring OCS). For subjects starting with 35 mg/day at baseline, the maximum possible reduction is 32.5 mg/day (i.e., minimum dose per protocol is 2.5 mg). Analysis was performed on ITT population.
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End point type |
Secondary
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End point timeframe |
Week 24
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Statistical analysis title |
Dupilumab 300 mg q2w vs. Placebo q2w | ||||||||||||
Statistical analysis description |
The endpoint was analyzed using a logistic regression model. The model included binary status of whether or not a subject achieved their maximum possible reduction of OCS dose per protocol at Week 24 as the response variable, treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed by using a pattern mixture model by multiple imputation approach.
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Comparison groups |
Dupilumab 300 mg q2w v Placebo q2w
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Number of subjects included in analysis |
210
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Analysis specification |
Pre-specified
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Analysis type |
superiority [8] | ||||||||||||
P-value |
= 0.0024 [9] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
2.57
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.4 | ||||||||||||
upper limit |
4.73 | ||||||||||||
Notes [8] - Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant). [9] - Threshold for significance at 0.05. |
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End point title |
Percentage of Subjects Who No Longer Require Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control | ||||||||||||
End point description |
Subjects were classified according to the binary status of whether or not the subject still requires OCS at week 24 while maintaining asthma control. Analysis was performed on ITT population with baseline OCS dose less than or equal to 30 mg/day.
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End point type |
Secondary
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End point timeframe |
Week 24
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Statistical analysis title |
Dupilumab 300 mg q2w vs. Placebo q2w | ||||||||||||
Statistical analysis description |
The endpoint was analyzed using a logistic regression model. The model included the binary status of whether or not a subject no longer required OCS at Week 24 as the response variable, and treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed using a pattern mixture model by multiple imputation approach.
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Comparison groups |
Dupilumab 300 mg q2w v Placebo q2w
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Number of subjects included in analysis |
209
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Analysis specification |
Pre-specified
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Analysis type |
superiority [10] | ||||||||||||
P-value |
= 0.0015 [11] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
2.74
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.47 | ||||||||||||
upper limit |
5.1 | ||||||||||||
Notes [10] - Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant). [11] - Threshold for significance at 0.05. |
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End point title |
Absolute Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control | |||||||||||||||||||||
End point description |
Absolute reduction was calculated by subtracting Week 24 value from baseline value . Analysis was performed on ITT population but not included in the hierarchical testing procedure. Here, "n"= subjects with available data for specified categories.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Asthma Control Questionnaire 5-Question Version (ACQ-5) Score at Weeks 2, 4, 8, 12, 16, 20, and 24 | |||||||||||||||||||||||||||||||||
End point description |
The ACQ-5 has 5 questions, reflecting top-scoring 5 asthma symptoms: woken at night by symptoms, wake in mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Subjects were asked to recall how their asthma had been during previous week and to respond to each of 5 symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total score was mean of scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control. Analysis was performed on ITT population. Here, n= subjects with available data for specified categories.
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End point type |
Other pre-specified
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End point timeframe |
Baseline and at Weeks 2, 4, 8, 12, 16, 20, and 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12 and Week 24 | ||||||||||||||||||
End point description |
AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that were most important to subjects with asthma. AQLQ comprised of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item was scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire were averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life. Analysis was performed on ITT population. Here, n= subjects with available data for specified categories.
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End point type |
Other pre-specified
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End point timeframe |
Baseline, Week 12 and Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Scores at Week 12 and Week 24 | ||||||||||||||||||||||||
End point description |
EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L-VAS records subject’s self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable). Analysis was performed on ITT population. Here, “n”=subjects with available data for specified categories.
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End point type |
Other pre-specified
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End point timeframe |
Baseline, Week 12 and Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 12 and Week 24 | ||||||||||||||||||
End point description |
The HADS is a general scale to detect states of anxiety and depression already used and validated in asthma, which includes HADS-A and HADS-D subscales. The instrument is comprised of 14 items: 7 related to anxiety (HADS-A) and 7 to depression (HADS-D). Each item on the questionnaire is scored from 0-3. And, the total score is the sum of the scores of the 14 items ranging from 0 (no symptoms) to 42 (severe symptoms), with higher scores indicating higher anxiety/depression complains. Analysis was performed on ITT population. Here, "n" signifies number of subjects with available data for specified categories.
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End point type |
Other pre-specified
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End point timeframe |
Baseline, Week 12 and Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Sino Nasal Outcome Test-22 (SNOT-22) Global Score at Week 12 and Week 24 | ||||||||||||||||||
End point description |
The SNOT-22 is a validated measure of health related quality of life in sino nasal disease. It is a 22 item questionnaire with each item assigned a score ranging from 0-5. The total score may range from 0 (no disease) -110 (worst disease), lower scores represent better health related quality of life. Analysis was performed on ITT population with bilateral nasal polyposis/chronic rhinosinusitis. Here "n" = subjects with available data for specified categories.
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End point type |
Other pre-specified
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End point timeframe |
Baseline, Week 12 and Week 24
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No statistical analyses for this end point |
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End point title |
Annualized Rate of Severe Exacerbation Events During The 24-Week Treatment Period | ||||||||||||
End point description |
A severe asthma exacerbation event was defined as a deterioration of asthma during the 24-week treatment period requiring: use of systemic corticosteroids for >=3 days (at least double the dose currently used); and/or hospitalization related to asthma symptoms or emergency room visit because of asthma requiring intervention with a systemic corticosteroid treatment. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of subject-years treated. Analysis was performed on ITT population.
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End point type |
Other pre-specified
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End point timeframe |
Baseline to Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Weeks 12 and 24 | |||||||||||||||||||||||||||
End point description |
FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Analysis was performed on ITT population. Here, “n”= subjects with available data for specified categories.
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End point type |
Other pre-specified
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End point timeframe |
Baseline, Week 12 and Week 24
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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 |
All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 36) regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
Reported AEs were treatment emergent (TE) AEs developed/worsened during 'TE period' (from first dose of study drug injection until 98 days after last dose of drug or entry in LTS12551 study). Safety population included all subjects who actually received at least 1 dose/part of a dose of IMP and analyzed according to treatment actually received.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Placebo q2w
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Reporting group description |
Subjects who received Placebo (for Dupilumab) in combination with OCS and stable ICS (mean exposure of 24 weeks). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Dupilumab 300mg q2w
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Reporting group description |
Subjects who received Dupilumab 300 mg q2w in combination with OCS and stable ICS (mean exposure of 24 weeks). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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20 Jul 2016 |
Following changes were made: - Added instructions to allow the investigator to stop the downward titration of OCS in case of a
safety concern; - Modified the forced expiratory volume in 1 second (FEV1) inclusion criteria for screening period and prior to randomization; - Deleted the exclusion criteria on birth control for male subjects with a female partner of childbearing potential; - Modification of the definition of the adverse events of special interest (AESIs) for infections, opportunistic infections, and the reporting requirements for systemic allergic reactions related to IMP and requiring treatment; - Updated the list of controller medications; - Modified the criteria for temporary treatment discontinuation to include infection and infestation that do not respond to medical treatment and updated the list of criteria for permanent
treatment discontinuation to be consistent with changes to AESI criteria; - Provided clarification of hepatitis serology testing and interpretation of the results in context of eligibility criteria; - Added chest X-Ray or magnetic resonance imaging (MRI) at Visit 10 for subjects who planned to roll over into a long term study. |
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25 Jan 2017 |
Following changes were made: Increased the number of subjects to be enrolled from 150 to 180. |
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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 |