Trial Outcomes & Findings for Continuation of TRAVERSE- LTS12551 Evaluating Dupilumab Safety in Patients With Asthma (Long-Term Follow-Up) (NCT NCT03620747)
NCT ID: NCT03620747
Last Updated: 2023-03-16
Results Overview
An adverse event (AE) was defined as any untoward medical occurrence in a participant 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).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
393 participants
Primary outcome timeframe
From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
Results posted on
2023-03-16
Participant Flow
The study was conducted at 138 sites in 10 countries. A total of 393 participants were enrolled in the study between 30 August 2018 and 27 August 2020.
Participants with moderate to severe asthma who had completed the parent study TRAVERSE-LTS12551 (NCT02134028) were enrolled in this current study (LPS15023).
Participant milestones
| Measure |
Dupilumab
Participants received subcutaneous (SC) dose of dupilumab 300 milligrams (mg) every 2 weeks (q2w) from Week 0 up to Week 132. Participants 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. Participants were also on background dose of medium or high dose inhaled corticosteroid (ICS) as maintained in study LTS12551 in combination with controllers (and/or oral corticosteroid \[OCS\] for those participants from the original parent study EFC13691 \[NCT02528214\]). Salbutamol/albuterol hydrofluoroalkane pressurized metered dose inhalers (MDI) or levosalbutamol/levalbuterol hydrofluoroalkane pressurized MDI were given as reliever medication as needed during the study.
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|---|---|
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Overall Study
STARTED
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393
|
|
Overall Study
COMPLETED
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374
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Overall Study
NOT COMPLETED
|
19
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Reasons for withdrawal
| Measure |
Dupilumab
Participants received subcutaneous (SC) dose of dupilumab 300 milligrams (mg) every 2 weeks (q2w) from Week 0 up to Week 132. Participants 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. Participants were also on background dose of medium or high dose inhaled corticosteroid (ICS) as maintained in study LTS12551 in combination with controllers (and/or oral corticosteroid \[OCS\] for those participants from the original parent study EFC13691 \[NCT02528214\]). Salbutamol/albuterol hydrofluoroalkane pressurized metered dose inhalers (MDI) or levosalbutamol/levalbuterol hydrofluoroalkane pressurized MDI were given as reliever medication as needed during the study.
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|---|---|
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Overall Study
Participant decision
|
7
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Overall Study
Adverse Event
|
6
|
|
Overall Study
Lack of Efficacy
|
1
|
|
Overall Study
Poor compliance to protocol
|
2
|
|
Overall Study
Other-unspecified
|
3
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Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Dupilumab
n=393 Participants
Participants received SC dose of dupilumab 300 mg q2w from Week 0 up to Week 132. Participants who discontinued treatment for \>= 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Participants 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 participants from the original parent study EFC13691). Salbutamol/albuterol hydrofluoroalkane pressurized MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurized MDI were given as reliever medication as needed during the study.
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|---|---|
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Age, Continuous
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52.1 years
STANDARD_DEVIATION 14.19 • n=393 Participants
|
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Sex: Female, Male
Female
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231 Participants
n=393 Participants
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Sex: Female, Male
Male
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162 Participants
n=393 Participants
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PRIMARY outcome
Timeframe: From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)Population: Analysis was performed on safety population that included all participants who had actually received at least one dose or part of a dose of IMP.
An adverse event (AE) was defined as any untoward medical occurrence in a participant 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).
Outcome measures
| Measure |
Dupilumab
n=393 Participants
Participants received SC dose of dupilumab 300 mg q2w from Week 0 up to Week 132. Participants who discontinued treatment for \>= 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Participants 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 participants from the original parent study EFC13691). Salbutamol/albuterol hydrofluoroalkane pressurized MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurized MDI were given as reliever medication as needed during the study.
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|---|---|
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Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
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54.5 percentage of participants
Interval 47.4 to 62.26
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PRIMARY outcome
Timeframe: From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)Population: Analysis was performed on safety population.
An AE was defined as any untoward medical occurrence in a participant 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). TEAE event rate was defined as the number of TEAE events per 100 participant-years.
Outcome measures
| Measure |
Dupilumab
n=393 Participants
Participants received SC dose of dupilumab 300 mg q2w from Week 0 up to Week 132. Participants who discontinued treatment for \>= 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Participants 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 participants from the original parent study EFC13691). Salbutamol/albuterol hydrofluoroalkane pressurized MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurized MDI were given as reliever medication as needed during the study.
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|---|---|
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Treatment-emergent Adverse Event Rate (Event Per 100 Participant-years)
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171.4 events per 100 participant-years
Interval 162.71 to 180.43
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SECONDARY outcome
Timeframe: From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)Population: Analysis was performed on safety population.
An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. AESIs were AE (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 participant-years.
Outcome measures
| Measure |
Dupilumab
n=393 Participants
Participants received SC dose of dupilumab 300 mg q2w from Week 0 up to Week 132. Participants who discontinued treatment for \>= 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Participants 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 participants from the original parent study EFC13691). Salbutamol/albuterol hydrofluoroalkane pressurized MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurized MDI were given as reliever medication as needed during the study.
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|---|---|
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Adverse Events of Special Interest (AESIs) Event Rate (Event Per100 Participant-years)
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6.0 events per 100 participant-years
Interval 4.4 to 7.99
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SECONDARY outcome
Timeframe: From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)Population: Analysis was performed on safety population.
AE: any untoward medical occurrence in participants that received IMP and did not necessarily had to have causal relationship with treatment. TEAEs: AEs developed/worsened in grade/become serious during the TEAE period (from first dose of IMP up to 12 weeks after last dose of IMP).SAE: any untoward medical occurrence at any dose resulted in death, was life-threatening, required inpatient hospitalization, prolongation of existing hospitalization, 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.
Outcome measures
| Measure |
Dupilumab
n=393 Participants
Participants received SC dose of dupilumab 300 mg q2w from Week 0 up to Week 132. Participants who discontinued treatment for \>= 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Participants 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 participants from the original parent study EFC13691). Salbutamol/albuterol hydrofluoroalkane pressurized MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurized MDI were given as reliever medication as needed during the study.
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Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and AEs Leading to Study Discontinuation
TESAEs
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5.6 percentage of participants
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Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and AEs Leading to Study Discontinuation
AESIs
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6.1 percentage of participants
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Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and AEs Leading to Study Discontinuation
AEs leading to study discontinuation
|
1.5 percentage of participants
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Adverse Events
Dupilumab
Serious events: 22 serious events
Other events: 93 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Dupilumab
n=393 participants at risk
Participants received SC dose of dupilumab 300 mg q2w from Week 0 up to Week 132. Participants who discontinued treatment for \>= 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Participants 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 participants from the original parent study EFC13691). Salbutamol/albuterol hydrofluoroalkane pressurized MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurized MDI were given as reliever medication as needed during the study.
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|---|---|
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Cardiac disorders
Cardiac failure congestive
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Cardiac disorders
Myocardial infarction
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Nervous system disorders
Epilepsy
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Nervous system disorders
Pudendal canal syndrome
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Eye disorders
Cataract
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Respiratory, thoracic and mediastinal disorders
Asthma
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1.0%
4/393 • Number of events 5 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Respiratory, thoracic and mediastinal disorders
Respiratory failure
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Respiratory, thoracic and mediastinal disorders
Tracheal stenosis
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Gastrointestinal disorders
Abdominal pain
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Gastrointestinal disorders
Enterovesical fistula
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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|
Gastrointestinal disorders
Hiatus hernia
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Gastrointestinal disorders
Pancreatitis
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Infections and infestations
Bronchitis
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Infections and infestations
COVID-19
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0.76%
3/393 • Number of events 3 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Infections and infestations
COVID-19 pneumonia
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0.76%
3/393 • Number of events 3 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Infections and infestations
Pneumonia
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Infections and infestations
Urinary tract infection
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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General disorders
Non-cardiac chest pain
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Immune system disorders
Anaphylactic reaction
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0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.25%
1/393 • Number of events 1 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Other adverse events
| Measure |
Dupilumab
n=393 participants at risk
Participants received SC dose of dupilumab 300 mg q2w from Week 0 up to Week 132. Participants who discontinued treatment for \>= 6 weeks after study LTS12551, received a 600 mg loading dose of dupilumab on Week 0. Participants 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 participants from the original parent study EFC13691). Salbutamol/albuterol hydrofluoroalkane pressurized MDI or levosalbutamol/levalbuterol hydrofluoroalkane pressurized MDI were given as reliever medication as needed during the study.
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|---|---|
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Respiratory, thoracic and mediastinal disorders
Asthma
|
13.2%
52/393 • Number of events 77 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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.
|
|
Infections and infestations
COVID-19
|
5.6%
22/393 • Number of events 24 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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.
|
|
Infections and infestations
Nasopharyngitis
|
8.4%
33/393 • Number of events 36 • From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks)
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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Additional Information
Trial Transparency Team
Sanofi aventis recherche & développement
Phone: 800-633-1610
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
- Publication restrictions are in place
Restriction type: OTHER