Clinical Trial Results:
Open-label, Interventional, Cohort Study to Evaluate Long-term Safety of Dupilumab in Patients with Moderate to Severe Asthma who Completed the TRAVERSE-LTS12551 Clinical Trial
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Summary
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EudraCT number |
2017-002134-23 |
Trial protocol |
FR BE DE NL Outside EU/EEA |
Global end of trial date |
18 Feb 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Sep 2022
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First version publication date |
02 Sep 2022
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Other versions |
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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 |
LPS15023
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03620747 | ||
WHO universal trial number (UTN) |
U1111-1196-5369 | ||
Other trial identifiers |
Study name: TRAVERSE-LPS15023 | ||
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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 |
28 Mar 2022
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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 |
18 Feb 2022
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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 describe the long-term safety of dupilumab in treatment of subjects with moderate to severe asthma who completed the previous asthma clinical trial (TRAVERSE-LTS12551 [EudraCT number: 2013-003856-19]).
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Protection of trial subjects |
The study was conducted by investigators experienced in the treatment of adult and adolescent subjects. The parent(s) or guardian(s) 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 minimised. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimise distress and discomfort. Adult 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. 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 |
Subjects continued background therapy of moderate or high-dose inhaled corticosteroid (ICS) as maintained in TRAVERSE-LTS12551. Background therapy was modified during the study based on Investigator's judgment. Subjects used additional asthma controller therapies initiated during TRAVERSE-LTS12551. Subjects received salbutamol/albuterol hydrofluoroalkane pressurised metered dose inhalers (MDI) or levosalbutamol/levalbuterol hydrofluoroalkane pressurised MDI as reliever medication during the LPS15023 study. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Aug 2018
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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 |
Netherlands: 1
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
France: 23
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Country: Number of subjects enrolled |
Germany: 19
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Country: Number of subjects enrolled |
South Africa: 33
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Country: Number of subjects enrolled |
Israel: 7
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Country: Number of subjects enrolled |
Canada: 26
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Country: Number of subjects enrolled |
Argentina: 113
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Country: Number of subjects enrolled |
Japan: 103
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Country: Number of subjects enrolled |
United States: 67
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Worldwide total number of subjects |
393
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EEA total number of subjects |
44
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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) |
8
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Adults (18-64 years) |
306
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From 65 to 84 years |
79
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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 138 sites in 10 countries. A total of 393 subjects were enrolled in the study between 30 August 2018 and 27 August 2020. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects with moderate to severe asthma who had completed the parent study TRAVERSE-LTS12551 were enrolled in this current study (LPS15023). | ||||||||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Dupilumab | ||||||||||||||||||
Arm description |
Subjects received subcutaneous (SC) dose of dupilumab 300 milligrams (mg) every 2 weeks (q2w) from Week 0 up to Week 132. Subjects who discontinued treatment for greater than or equal to [>=] 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Subjects were also on background dose of medium or high dose ICS as maintained in study LTS12551 in combination with controllers (and/or oral corticosteroid [OCS] for those subjects from the original parent study EFC13691 [EudraCT number: 2015-001573-40]). Salbutamol/albuterol hydrofluoroalkane pressurised MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurised MDI were given as reliever medication as needed during the study. | ||||||||||||||||||
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 |
Subjects received dupilumab 300 mg SC injection q2w for up to 132 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Dupilumab
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Reporting group description |
Subjects received subcutaneous (SC) dose of dupilumab 300 milligrams (mg) every 2 weeks (q2w) from Week 0 up to Week 132. Subjects who discontinued treatment for greater than or equal to [>=] 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Subjects were also on background dose of medium or high dose ICS as maintained in study LTS12551 in combination with controllers (and/or oral corticosteroid [OCS] for those subjects from the original parent study EFC13691 [EudraCT number: 2015-001573-40]). Salbutamol/albuterol hydrofluoroalkane pressurised MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurised MDI were given as reliever medication as needed during the study. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Dupilumab
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Reporting group description |
Subjects received subcutaneous (SC) dose of dupilumab 300 milligrams (mg) every 2 weeks (q2w) from Week 0 up to Week 132. Subjects who discontinued treatment for greater than or equal to [>=] 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Subjects were also on background dose of medium or high dose ICS as maintained in study LTS12551 in combination with controllers (and/or oral corticosteroid [OCS] for those subjects from the original parent study EFC13691 [EudraCT number: 2015-001573-40]). Salbutamol/albuterol hydrofluoroalkane pressurised MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurised MDI were given as reliever medication as needed during the study. | ||
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End point title |
Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs) [1] | ||||||||
End point description |
An Adverse Event (AE) was defined as any untoward medical occurrence in a subject who received study drug and did not necessarily had to have a causal relationship with the treatment. TEAEs were the AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the investigational medicinal product [IMP] up to 12 weeks after the last dose of the IMP [maximum duration: up to 144 weeks]). Analysis was performed on safety population that included all subjects who had received at least one dose or part of a dose of IMP during the current study.
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End point type |
Primary
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End point timeframe |
From first dose of (IMP) up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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| Notes [1] - 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: As the endpoint was descriptive in nature, no statistical analysis was reported. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Treatment-emergent Adverse Event Rate (Events/100 Person-years) [2] | ||||||||
End point description |
An AE was defined as any untoward medical occurrence in a subject who received study drug and did not necessarily had to have a causal relationship with the treatment. TEAEs were the AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the IMP up to 12 weeks after last dose of the IMP [maximum duration: up to 144 weeks]). TEAE event rate was defined as the number of TEAE events per 100 person-years. Analysis was performed on safety population.
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End point type |
Primary
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End point timeframe |
From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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| Notes [2] - 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: As the endpoint was descriptive in nature, no statistical analysis was reported. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Adverse Events of Special Interest (AESIs) Event Rate (Events/100 Person-years) | ||||||||
End point description |
An AE was defined as any untoward medical occurrence in a subject who received study drug and did not necessarily had to have a causal relationship with the treatment. AESI were AEs (serious or non-serious) of scientific and medical concern specific to the Sponsor’s product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. AESI event rate was defined as the number of AESI events per 100 person-years. Analysis was performed on safety population.
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End point type |
Secondary
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End point timeframe |
From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Treatment-emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and AEs Leading to Study Discontinuation | ||||||||||||||
End point description |
AE: any untoward medical occurrence in subjects that received IMP and did not necessarily had to have causal relationship with treatment. TEAEs: AEs developed/worsened in grade/become serious during TEAE period (from first dose of IMP up to 12 weeks after last dose of IMP [maximum duration: up to 144 Weeks]). SAE: any untoward medical occurrence at any dose resulted in death, was life-threatening, required inpatient hospitalisation, prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically important event. AESI:AE (serious/non-serious) of scientific and medical concern specific to Sponsor's product/program, for which ongoing monitoring and immediate notification by Investigator to Sponsor required. Analysis was performed on safety population.
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End point type |
Secondary
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End point timeframe |
From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 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 IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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Adverse event reporting additional description |
Reported AEs and deaths were TEAEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the IMP up to 12 weeks after last dose of the IMP). Analysis was performed on safety population.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
Dupilumab
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Reporting group description |
Subjects received SC dose of dupilumab 300 mg q2w from Week 0 up to Week 132. Subjects who discontinued treatment for >= 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Subjects were also on background dose of medium or high dose ICS as maintained in study LTS12551 in combination with controllers (and/or OCS for those subjects from the original parent study EFC13691). Salbutamol/albuterol hydrofluoroalkane pressurised MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurised MDI were given as reliever medication as needed during the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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 | |||
