Asthma
Conditions
Brief summary
Primary Objective: To describe the long-term safety of dupilumab in treatment of participants with moderate to severe asthma who completed the previous asthma clinical trial (TRAVERSE-LTS12551).
Detailed description
Duration per participant was until dupilumab approval for use in asthma and market availability to the participant, or a maximum of 144 weeks (i.e., about 3 years) after the start of treatment (Visit 1), whichever came first.
Interventions
Pharmaceutical form: prefilled syringes Route of administration: subcutaneous
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with asthma who completed the treatment period in the previous dupilumab asthma clinical study LTS12551. * Signed written informed consent.
Exclusion criteria
* Participants who experienced any systemic hypersensitivity reactions to the investigational medicinal product in the previous dupilumab asthma study LTS12551, which, in the opinion of the Investigator, could indicate that continued treatment with dupilumab might present an unreasonable risk for the participant. * Clinically significant comorbidity/lung disease other than asthma. * Participants with active autoimmune disease or participants who, as per Investigator's medical judgment, were suspected of having high risk for developing autoimmune disease. * History of malignancy within 5 years before enrollment except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks) | 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). |
| Treatment-emergent Adverse Event Rate (Event Per 100 Participant-years) | From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events of Special Interest (AESIs) Event Rate (Event Per100 Participant-years) | From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks) | 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. |
| Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and AEs Leading to Study Discontinuation | From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks) | 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. |
Countries
Argentina, Belgium, Canada, France, Germany, Israel, Japan, Netherlands, South Africa, United States
Participant flow
Recruitment details
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.
Pre-assignment details
Participants with moderate to severe asthma who had completed the parent study TRAVERSE-LTS12551 (NCT02134028) were enrolled in this current study (LPS15023).
Participants by arm
| Arm | Count |
|---|---|
| Dupilumab 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. | 393 |
| Total | 393 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Other-unspecified | 3 |
| Overall Study | Participant decision | 7 |
| Overall Study | Poor compliance to protocol | 2 |
Baseline characteristics
| Characteristic | Dupilumab | — |
|---|---|---|
| Age, Continuous | 52.1 years STANDARD_DEVIATION 14.19 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 231 Participants | — |
| Sex: Female, Male Male | 162 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 393 |
| other Total, other adverse events | 93 / 393 |
| serious Total, serious adverse events | 22 / 393 |
Outcome results
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
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).
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 54.5 percentage of participants |
Primary
Treatment-emergent Adverse Event Rate (Event Per 100 Participant-years)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Treatment-emergent Adverse Event Rate (Event Per 100 Participant-years) | 171.4 events per 100 participant-years |
Secondary
Adverse Events of Special Interest (AESIs) Event Rate (Event Per100 Participant-years)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Adverse Events of Special Interest (AESIs) Event Rate (Event Per100 Participant-years) | 6.0 events per 100 participant-years |
Secondary
Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and AEs Leading to Study Discontinuation
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dupilumab | Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and AEs Leading to Study Discontinuation | TESAEs | 5.6 percentage of participants |
| Dupilumab | Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and AEs Leading to Study Discontinuation | AESIs | 6.1 percentage of participants |
| Dupilumab | 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 |