Asthma
Conditions
Brief summary
Primary Objective: * To evaluate the long-term safety and tolerability of dupilumab in pediatric patients with asthma who participated in a previous dupilumab asthma clinical study. * To evaluate the efficacy of dupilumab in children of 6 to \<12 years of age with uncontrolled persistent asthma in the Japan sub-study. Secondary Objectives: * To evaluate the long-term efficacy of dupilumab in pediatric patients with asthma who participated in a previous dupilumab asthma clinical study. * To evaluate dupilumab in pediatric patients with asthma who participated in a previous dupilumab asthma clinical study with regard to: * Systemic exposure. * Anti-drug antibodies (ADAs). * Biomarkers. * To evaluate the safety and tolerability of dupilumab in pediatric patients with asthma in the Japan sub-study * To evaluate dupilumab in pediatric patients with asthma in the Japan substudy with regard to: * Systemic exposure, * Anti-drug antibodies (ADAs), * Biomarkers
Detailed description
Study duration per participant is approximatively 64 weeks including a 52 weeks treatment period and 12 weeks post treatment follow-up. Japan substudy: Study duration per participant is approximately 68 weeks including 3-5 weeks screening period, 52 weeks treatment period and 12 weeks post treatment follow-up period.
Interventions
DRUGDupilumab (SAR231893/REGN668)
Pharmaceutical form: solution for injection Route of administration: subcutaneous (sc)
DRUGAsthma controller therapies (incl. prednisone/prednisolone)
Pharmaceutical form: powder, or solution, or pill Route of administration: inhaled, oral or parenteral
Pharmaceutical form: powder or solution Route of administration: inhaled
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
: * Pediatric patients with asthma who completed the treatment in a dupilumab asthma trial (EFC14153). * Signed written informed consent/assent. Specific for Brazil: EFC14153 patients from Brazil, who prematurely discontinued Investigational Medicinal Product (IMP) to receive Yellow Fever vaccine (a live attenuated vaccine) during Yellow Fever outbreak, are allowed to be enrolled in LTS14424 after completing the required procedures in EFC14153 (completion of remaining visits and procedures until end of treatment (EOT) V28, considered as V1 for LTS14424). Patients who are not able to complete their treatment in Study EFC14153 due to the COVID-19 pandemic will be allowed to enroll into Study LTS14424. Patients who enroll in LTS14424 after completing the EFC14153 EOS visit should have eligibility for LTS14424 reevaluated including background medication check and laboratory assessments (including complete blood count \[CBC\] with differential and basic chemistry) within 1 month prior to LTS14424 Visit 1. For Japan sub-study * Signed written inform consent/assent * Children 6 to \<12 years of age, with a physician diagnosis of persistent asthma for ≥12 months prior to screening * Blood eosinophil count ≥150 cells/μL or fractional exhaled nitric oxide (FeNO) ≥20 parts per billion (ppb) at screening visit (Visit 0).
Exclusion criteria
* Any chronic lung disease other than asthma (eg, cystic fibrosis, bronchopulmonary dysplasia) which may impair lung function. * Inability to follow the procedures of the study/noncompliance (eg, due to language problems or psychological disorders). * Patients receiving concomitant treatment or required a new concomitant treatment prohibited in the study. * Patients or his/her parent(s)/caregiver(s)/legal guardian(s) is related to the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff thereof directly involved in the conduct of the study. * Patients who experienced any hypersensitivity reactions to dupilumab in a previous dupilumab study, which, in the opinion of the Investigator, could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient. * Any abnormalities or adverse events at screening (last treatment visit in the study EFC14153 will be the screening visit) that per Investigator judgment would adversely affect patient's participation in this study or would require permanent IMP discontinuation. * For female patients who have commenced menstruating at any time during the study and are either: * Found to have a positive urine pregnancy test, or * Sexually active, not using an established acceptable contraceptive method. * Planned live, attenuated vaccinations during the study. * Patients with active autoimmune disease or patients using immunosuppressive therapy for autoimmune disease (eg, juvenile idiopathic arthritis, inflammatory bowel disease, systemic lupus erythematosus) at enrollment. For Japan sub-study: * Any chronic lung disease other than asthma (eg, cystic fibrosis, bronchopulmonary dysplasia) which may impair lung function. * Inability to follow the procedures of the study/noncompliance (eg, due to language problems or psychological disorders). * Patients receiving concomitant treatment or required a new concomitant treatment prohibited in the study at the screening and enrollment visits. * Patients who previously have been treated with dupilumab * Diagnosed with active parasitic infection (helminthes); suspected or high risk of parasitic infection, unless clinical and (if necessary) laboratory assessments have ruled out active infection before randomization * Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis), despite infection resolution; or unusually frequent, recurrent, or prolonged infections, per Investigator's judgment. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Main Study: Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs) | From first dose of study treatment (Day 1) up to 112 days post last dose of study treatment, approximately 64 weeks | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. TEAEs were AEs that developed or worsened or became serious during the TEAE period. |
| Japan Sub-study: Change From Baseline to Week 12 in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) | Baseline (Day 1) to Week 12 | FEV1 was the volume of air (in liters) exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration. Baseline was defined as the last available measurement prior to the first study treatment dose if the participant was treated, or the last available value up to enrollment if the participant was not exposed to study treatment in the current study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Baseline (Day 1) and Weeks 2, 4 (Japan sub-study), 8, 12, 24, 52 and 64 | FEV1 was volume of air (in liters) exhaled from the lungs in first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration. Baseline (main study): original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in current study. |
| Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Baseline (Day 1) and Weeks 2, 4 (Japan sub-study), 8, 12, 24, 52 and 64 | FEV1 was volume of air (in liters) exhaled from the lungs in first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration. Baseline (main study): original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in current study. |
| Change From Baseline in Forced Vital Capacity (FVC) Over Time | Baseline (Day 1) and Weeks 2, 4 (Japan sub-study), 8, 12, 24, 52 and 64 | FVC was defined as volume of air (in liters) that could be forcibly blown out after full inspiration in upright position as measured by spirometer. Spirometry was performed after wash out period of bronchodilators according to their action duration. Baseline (main study):original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated or last available value up to enrollment if participant was not exposed to study treatment in current study. |
| Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Baseline (Day 1) and Weeks 2, 4 (Japan sub-study), 8, 12, 24, 52 and 64 | FEF was defined as amount of air which can be forcibly exhaled from lungs in first second of forced exhalation. FEF 25-75% was the mean FEF between 25% and 75% of FVC. FVC was defined as volume of air that could be forcibly blown out after full inspiration in upright position. Spirometry was performed after wash out period of bronchodilators. Baseline (main study): original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated or last available value up to enrollment if participant was not exposed to study treatment in current study. |
| Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Baseline (Day 1) and Weeks 2, 8, 12, 24, 52 and 64 | FVC was defined as volume of air (in liters) that could be forcibly blown out after full inspiration in upright position as measured by spirometer. Spirometry was performed after wash out period of bronchodilators according to their action duration. Baseline was defined as the original baseline of parent study EFC14153. |
| Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-Question Version (ACQ-7-IA) Over Time | Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, 52 and 64 | ACQ-7-IA had 7 questions with first 5 items of ACQ-7 addressing most common asthma symptoms: frequency in past week awoken by asthma during night, severity of asthma symptoms in morning, limitation of daily activities due to asthma, shortness of breath due to asthma, wheeze; 2 questions on short-acting bronchodilator use and predicted bronchodilator use of FEV1. Participants/parents/guardians recalled child's previous week asthma and responded to questions on 7-point scale: 0=no impairment, 6=maximum impairment. Global ACQ-7-IA score was the mean of 7 questions, ranging from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicated lower asthma control. Baseline: last available measurement prior to first study treatment dose if participant was treated or last available value up to enrollment if participant was not exposed to study treatment in current study. |
| Japan Sub-study: Number of Participants With Any Treatment-Emergent Adverse Events | From first dose of study treatment (Day 1) up to 112 days post last dose of study treatment, approximately 64 weeks | An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. TEAEs were AEs that developed or worsened or became serious during the TEAE period. |
| Serum Concentrations of Dupilumab | Weeks 12, 24, 52 and 64 | Blood samples were collected at the specified timepoints for determination of functional dupilumab concentration in serum. |
| Number of Participants With Anti-Drug Antibodies (ADAs) Against Dupilumab | From first dose of study treatment (Day 1) to Week 64 | ADA positive was defined as either treatment-boosted or treatment-emergent response in the ADA assay. Treatment-boosted response was defined as a positive response in the ADA assay post first dose in the current study that was greater than or equal to 4-fold of the baseline titer levels, when baseline results were positive. Treatment-emergent response was defined as a positive response in the ADA assay post first dose in the current study, when baseline results were negative or missing. Baseline (main study): original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in current study. |
| Main Study: Percent Change From Baseline in Blood Eosinophil Count at Week 64 | Baseline (Day 1) to Week 64 | Blood samples were collected at specified timepoints to assess percent change from baseline in eosinophil count. Baseline was defined as the original baseline of parent study EFC14153. |
| Percent Change From Baseline in Total Immunoglobulin (Ig) E in Serum at Week 64 | Baseline (Day 1) to Week 64 | Blood samples were collected at specified timepoints to assess percent change from baseline in total IgE in serum. Baseline (main study): the original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in current study. |
| Japan Sub-study: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 64 | Baseline (Day 1) to Week 64 | FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 milliliter per second. FeNO assessment was conducted prior to spirometry and following a fast of ≥1 hour. Baseline was defined as the last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in the current study. |
| Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-Question Version (ACQ-5-IA) Over Time | Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, 52 and 64 | The ACQ-5-IA had 5 questions addressing most common asthma symptoms: frequency in past week awoken by asthma during night, severity of asthma symptoms in morning, limitation of daily activities due to asthma, shortness of breath due to asthma and wheeze. Participants/parents/guardians recalled the child's previous week asthma and responded to symptom and bronchodilator use questions on a 7-point scale: 0=no impairment, 6=maximum impairment. Global ACQ-5-IA score was the mean of 5 questions, ranging from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control. Baseline: last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in current study. |
| Annualized Rate of Severe Asthma Exacerbation Events During the 52-Week Treatment Period | Up to Week 52 | A severe exacerbation event during study was defined as a deterioration of asthma requiring use of systemic corticosteroid (SCS) for ≥3 days or hospitalization/emergency room visit because of asthma, requiring SCS. Annualized severe exacerbation event rate was defined as total number of events that occurred during 52-week treatment period divided by total number of participant-years followed in 52-week treatment period. |
Countries
Argentina, Australia, Brazil, Canada, Chile, Colombia, Hungary, Italy, Japan, Lithuania, Mexico, Poland, Russia, South Africa, Spain, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
The main study was conducted at 70 centers in 17 countries, and the sub-study was conducted at 11 centers in Japan. 365 participants who rolled over from parent study EFC14153 (NCT02948959) were enrolled in the main study and 13 participants (not included in parent study EFC14153) were enrolled in Japan sub-study.
Pre-assignment details
All participants received dupilumab dose based on body weight in the main study and Japan sub-study. As pre-specified in the protocol and statistical analysis plan (SAP), the results are presented by study and treatment group, regardless of the dose regimen.
Participants by arm
| Arm | Count |
|---|---|
| Main Study: Placebo-Dupilumab Participants who received placebo matched to dupilumab in the parent study EFC14153 received dupilumab for 52 weeks in the main study as follows:
* 100 mg q2w as an SC injection or 300 mg q4w as an SC injection for participants with body weight ≤30 kg.
* 200 mg q2w as an SC injection for participants with body weight \>30 kg. Participants also received a stable-dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication as instructed by Investigator. | 125 |
| Main Study: Dupilumab-Dupilumab Participants who received dupilumab in the parent study EFC14153 received dupilumab for 52 weeks in the main study as follows:
* 100 mg q2w as an SC injection or 300 mg q4w as an SC injection for participants with body weight ≤30 kg.
* 200 mg q2w as an SC injection for participants with body weight \>30 kg. Participants also received a stable-dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication as instructed by Investigator. | 240 |
| Japan Sub-study: Dupilumab Participants received dupilumab for 52 weeks in the Japan sub-study as follows:
* 100 mg q2w as an SC injection or 300 mg q4w as an SC injection for participants with body weight ≥15 kg and ≤30 kg.
* 200 mg q2w as an SC injection for participants with body weight \>30 kg. Participants also received a stable-dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication as instructed by Investigator. | 13 |
| Total | 378 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Other | 6 | 8 | 1 |
| Overall Study | Poor Compliance to Protocol | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Main Study: Placebo-Dupilumab | Main Study: Dupilumab-Dupilumab | Japan Sub-study: Dupilumab | Total |
|---|---|---|---|---|
| Age, Continuous | 9.9 years STANDARD_DEVIATION 1.6 | 9.9 years STANDARD_DEVIATION 1.7 | 9.69 years STANDARD_DEVIATION 1.11 | 9.89 years STANDARD_DEVIATION 1.62 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 13 Participants | 14 Participants |
| Race/Ethnicity, Customized Black/of African Descent | 6 Participants | 9 Participants | 0 Participants | 15 Participants |
| Race/Ethnicity, Customized Caucasian/White | 111 Participants | 215 Participants | 0 Participants | 326 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 14 Participants | 0 Participants | 22 Participants |
| Sex: Female, Male Female | 46 Participants | 85 Participants | 4 Participants | 135 Participants |
| Sex: Female, Male Male | 79 Participants | 155 Participants | 9 Participants | 243 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 125 | 0 / 240 | 0 / 13 |
| other Total, other adverse events | 63 / 125 | 108 / 240 | 13 / 13 |
| serious Total, serious adverse events | 1 / 125 | 6 / 240 | 4 / 13 |
Outcome results
Primary
Japan Sub-study: Change From Baseline to Week 12 in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)
FEV1 was the volume of air (in liters) exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration. Baseline was defined as the last available measurement prior to the first study treatment dose if the participant was treated, or the last available value up to enrollment if the participant was not exposed to study treatment in the current study.
Time frame: Baseline (Day 1) to Week 12
Population: Intent-to-treat (ITT) population included all participants in the enrolled population in the current study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline to Week 12 in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) | 7.08 percent predicted FEV1 | Standard Deviation 6.78 |
Primary
Main Study: Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. TEAEs were AEs that developed or worsened or became serious during the TEAE period.
Time frame: From first dose of study treatment (Day 1) up to 112 days post last dose of study treatment, approximately 64 weeks
Population: Safety population included all participants exposed to at least 1 dose or part of a dose of the study treatment during current study regardless of the amount of treatment administered.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Placebo-Dupilumab | Main Study: Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs) | 85 Participants |
| Main Study: Dupilumab-Dupilumab | Main Study: Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs) | 147 Participants |
Secondary
Annualized Rate of Severe Asthma Exacerbation Events During the 52-Week Treatment Period
A severe exacerbation event during study was defined as a deterioration of asthma requiring use of systemic corticosteroid (SCS) for ≥3 days or hospitalization/emergency room visit because of asthma, requiring SCS. Annualized severe exacerbation event rate was defined as total number of events that occurred during 52-week treatment period divided by total number of participant-years followed in 52-week treatment period.
Time frame: Up to Week 52
Population: Main study: safety population included all participants exposed to at least 1 dose or part of a dose of study treatment during current study regardless of amount of treatment administered. Sub-study: ITT population included all participants in enrolled population in the current study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study: Placebo-Dupilumab | Annualized Rate of Severe Asthma Exacerbation Events During the 52-Week Treatment Period | 0.114 exacerbations per participant-years |
| Main Study: Dupilumab-Dupilumab | Annualized Rate of Severe Asthma Exacerbation Events During the 52-Week Treatment Period | 0.120 exacerbations per participant-years |
| Japan Sub-study: Dupilumab | Annualized Rate of Severe Asthma Exacerbation Events During the 52-Week Treatment Period | 0.462 exacerbations per participant-years |
Secondary
Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time
FEV1 was volume of air (in liters) exhaled from the lungs in first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration. Baseline (main study): original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in current study.
Time frame: Baseline (Day 1) and Weeks 2, 4 (Japan sub-study), 8, 12, 24, 52 and 64
Population: Main study: safety population included all participants exposed to at least 1 dose or part of a dose of study treatment during current study regardless of amount of treatment administered. Sub-study: ITT population included all participants in enrolled population in current study. Only participants with data collected at the specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Placebo-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 8 | 0.38 liter | Standard Deviation 0.32 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 12 | 0.41 liter | Standard Deviation 0.31 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 64 | 0.66 liter | Standard Deviation 0.45 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 24 | 0.46 liter | Standard Deviation 0.35 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 2 | 0.36 liter | Standard Deviation 0.32 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 52 | 0.62 liter | Standard Deviation 0.41 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 2 | 0.42 liter | Standard Deviation 0.38 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 64 | 0.70 liter | Standard Deviation 0.44 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 12 | 0.45 liter | Standard Deviation 0.36 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 8 | 0.47 liter | Standard Deviation 0.39 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 52 | 0.66 liter | Standard Deviation 0.41 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 24 | 0.51 liter | Standard Deviation 0.39 |
| Japan Sub-study: Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 24 | 0.15 liter | Standard Deviation 0.15 |
| Japan Sub-study: Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 8 | 0.12 liter | Standard Deviation 0.15 |
| Japan Sub-study: Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 52 | 0.34 liter | Standard Deviation 0.21 |
| Japan Sub-study: Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 64 | 0.25 liter | Standard Deviation 0.14 |
| Japan Sub-study: Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 2 | 0.13 liter | Standard Deviation 0.15 |
| Japan Sub-study: Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 4 | 0.13 liter | Standard Deviation 0.13 |
| Japan Sub-study: Dupilumab | Change From Baseline in Absolute Forced Expiratory Volume in 1 Second Over Time | Week 12 | 0.17 liter | Standard Deviation 0.13 |
Secondary
Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time
FEF was defined as amount of air which can be forcibly exhaled from lungs in first second of forced exhalation. FEF 25-75% was the mean FEF between 25% and 75% of FVC. FVC was defined as volume of air that could be forcibly blown out after full inspiration in upright position. Spirometry was performed after wash out period of bronchodilators. Baseline (main study): original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated or last available value up to enrollment if participant was not exposed to study treatment in current study.
Time frame: Baseline (Day 1) and Weeks 2, 4 (Japan sub-study), 8, 12, 24, 52 and 64
Population: Main study: safety population included all participants exposed to at least 1 dose or part of dose of study treatment during current regardless of amount of treatment administered. Sub-study: ITT population included all participants in enrolled population in current study. Only participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 2 | 0.49 liter per second | Standard Deviation 0.63 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 64 | 0.77 liter per second | Standard Deviation 0.78 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 24 | 0.58 liter per second | Standard Deviation 0.68 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 12 | 0.54 liter per second | Standard Deviation 0.6 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 8 | 0.48 liter per second | Standard Deviation 0.6 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 52 | 0.73 liter per second | Standard Deviation 0.75 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 24 | 0.66 liter per second | Standard Deviation 0.65 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 52 | 0.77 liter per second | Standard Deviation 0.67 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 64 | 0.79 liter per second | Standard Deviation 0.7 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 2 | 0.58 liter per second | Standard Deviation 0.66 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 8 | 0.62 liter per second | Standard Deviation 0.63 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 12 | 0.59 liter per second | Standard Deviation 0.61 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 24 | 0.15 liter per second | Standard Deviation 0.37 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 4 | 0.25 liter per second | Standard Deviation 0.23 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 8 | 0.15 liter per second | Standard Deviation 0.3 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 52 | 0.40 liter per second | Standard Deviation 0.46 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 12 | 0.29 liter per second | Standard Deviation 0.31 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 64 | 0.11 liter per second | Standard Deviation 0.34 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Expiratory Flow [FEF] 25% to 75% Over Time | Week 2 | 0.21 liter per second | Standard Deviation 0.26 |
Secondary
Change From Baseline in Forced Vital Capacity (FVC) Over Time
FVC was defined as volume of air (in liters) that could be forcibly blown out after full inspiration in upright position as measured by spirometer. Spirometry was performed after wash out period of bronchodilators according to their action duration. Baseline (main study):original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated or last available value up to enrollment if participant was not exposed to study treatment in current study.
Time frame: Baseline (Day 1) and Weeks 2, 4 (Japan sub-study), 8, 12, 24, 52 and 64
Population: Main study: safety population included all participants exposed to at least 1 dose or part of a dose of study treatment during current study regardless of amount of treatment administered. Sub-study: ITT population included all participants in enrolled population in current study. Only participants with data collected at the specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 2 | 0.35 liter | Standard Deviation 0.29 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 8 | 0.37 liter | Standard Deviation 0.3 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 12 | 0.40 liter | Standard Deviation 0.3 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 24 | 0.47 liter | Standard Deviation 0.36 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 52 | 0.68 liter | Standard Deviation 0.42 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 64 | 0.74 liter | Standard Deviation 0.49 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 8 | 0.45 liter | Standard Deviation 0.42 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 12 | 0.43 liter | Standard Deviation 0.39 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 64 | 0.75 liter | Standard Deviation 0.48 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 52 | 0.70 liter | Standard Deviation 0.45 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 24 | 0.50 liter | Standard Deviation 0.4 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 2 | 0.38 liter | Standard Deviation 0.38 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 4 | 0.09 liter | Standard Deviation 0.12 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 24 | 0.17 liter | Standard Deviation 0.15 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 52 | 0.36 liter | Standard Deviation 0.22 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 8 | 0.11 liter | Standard Deviation 0.14 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 2 | 0.11 liter | Standard Deviation 0.15 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 64 | 0.41 liter | Standard Deviation 0.24 |
| Japan Sub-study: Dupilumab | Change From Baseline in Forced Vital Capacity (FVC) Over Time | Week 12 | 0.12 liter | Standard Deviation 0.11 |
Secondary
Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time
FEV1 was volume of air (in liters) exhaled from the lungs in first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration. Baseline (main study): original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in current study.
Time frame: Baseline (Day 1) and Weeks 2, 4 (Japan sub-study), 8, 12, 24, 52 and 64
Population: Main study: safety population included all participants exposed to at least 1 dose or part of a dose of study treatment during current study regardless of amount of treatment administered. Sub-study: ITT population included all participants in enrolled population in current study. Only participants with data collected at the specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Placebo-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 2 | 8.06 percent predicted FEV1 | Standard Deviation 15.71 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 8 | 7.93 percent predicted FEV1 | Standard Deviation 14.88 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 12 | 8.31 percent predicted FEV1 | Standard Deviation 14.7 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 52 | 8.81 percent predicted FEV1 | Standard Deviation 16.18 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 64 | 7.98 percent predicted FEV1 | Standard Deviation 17.14 |
| Main Study: Placebo-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 24 | 8.37 percent predicted FEV1 | Standard Deviation 15.48 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 8 | 12.47 percent predicted FEV1 | Standard Deviation 18.6 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 24 | 11.23 percent predicted FEV1 | Standard Deviation 18.24 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 52 | 12.19 percent predicted FEV1 | Standard Deviation 17.88 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 64 | 10.67 percent predicted FEV1 | Standard Deviation 17.19 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 12 | 10.95 percent predicted FEV1 | Standard Deviation 17.33 |
| Main Study: Dupilumab-Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 2 | 11.03 percent predicted FEV1 | Standard Deviation 18.74 |
| Japan Sub-study: Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 4 | 7.00 percent predicted FEV1 | Standard Deviation 7.12 |
| Japan Sub-study: Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 64 | 1.17 percent predicted FEV1 | Standard Deviation 8.03 |
| Japan Sub-study: Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 8 | 6.31 percent predicted FEV1 | Standard Deviation 8.97 |
| Japan Sub-study: Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 12 | 7.08 percent predicted FEV1 | Standard Deviation 6.78 |
| Japan Sub-study: Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 24 | 4.08 percent predicted FEV1 | Standard Deviation 8.75 |
| Japan Sub-study: Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 2 | 7.50 percent predicted FEV1 | Standard Deviation 9.29 |
| Japan Sub-study: Dupilumab | Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second Over Time | Week 52 | 6.73 percent predicted FEV1 | Standard Deviation 8.09 |
Secondary
Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-Question Version (ACQ-5-IA) Over Time
The ACQ-5-IA had 5 questions addressing most common asthma symptoms: frequency in past week awoken by asthma during night, severity of asthma symptoms in morning, limitation of daily activities due to asthma, shortness of breath due to asthma and wheeze. Participants/parents/guardians recalled the child's previous week asthma and responded to symptom and bronchodilator use questions on a 7-point scale: 0=no impairment, 6=maximum impairment. Global ACQ-5-IA score was the mean of 5 questions, ranging from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control. Baseline: last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in current study.
Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, 52 and 64
Population: ITT population included all participants in enrolled population in current study. Only participants with data collected at specified timepoints are reported
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-Question Version (ACQ-5-IA) Over Time | Week 2 | -0.68 score on a scale | Standard Deviation 0.87 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-Question Version (ACQ-5-IA) Over Time | Week 8 | -0.92 score on a scale | Standard Deviation 0.82 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-Question Version (ACQ-5-IA) Over Time | Week 12 | -1.20 score on a scale | Standard Deviation 0.84 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-Question Version (ACQ-5-IA) Over Time | Week 24 | -1.15 score on a scale | Standard Deviation 0.68 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-Question Version (ACQ-5-IA) Over Time | Week 36 | -1.25 score on a scale | Standard Deviation 0.54 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-Question Version (ACQ-5-IA) Over Time | Week 52 | -1.49 score on a scale | Standard Deviation 0.54 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-Question Version (ACQ-5-IA) Over Time | Week 4 | -0.75 score on a scale | Standard Deviation 1.06 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-Question Version (ACQ-5-IA) Over Time | Week 64 | -1.28 score on a scale | Standard Deviation 0.59 |
Secondary
Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-Question Version (ACQ-7-IA) Over Time
ACQ-7-IA had 7 questions with first 5 items of ACQ-7 addressing most common asthma symptoms: frequency in past week awoken by asthma during night, severity of asthma symptoms in morning, limitation of daily activities due to asthma, shortness of breath due to asthma, wheeze; 2 questions on short-acting bronchodilator use and predicted bronchodilator use of FEV1. Participants/parents/guardians recalled child's previous week asthma and responded to questions on 7-point scale: 0=no impairment, 6=maximum impairment. Global ACQ-7-IA score was the mean of 7 questions, ranging from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicated lower asthma control. Baseline: last available measurement prior to first study treatment dose if participant was treated or last available value up to enrollment if participant was not exposed to study treatment in current study.
Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, 52 and 64
Population: ITT population included all participants in enrolled population in current study. Only participants with data collected at specified timepoints are reported
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-Question Version (ACQ-7-IA) Over Time | Week 8 | -0.84 score on a scale | Standard Deviation 0.59 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-Question Version (ACQ-7-IA) Over Time | Week 12 | -1.03 score on a scale | Standard Deviation 0.66 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-Question Version (ACQ-7-IA) Over Time | Week 24 | -0.96 score on a scale | Standard Deviation 0.61 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-Question Version (ACQ-7-IA) Over Time | Week 36 | -1.01 score on a scale | Standard Deviation 0.47 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-Question Version (ACQ-7-IA) Over Time | Week 52 | -1.21 score on a scale | Standard Deviation 0.37 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-Question Version (ACQ-7-IA) Over Time | Week 64 | -0.99 score on a scale | Standard Deviation 0.52 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-Question Version (ACQ-7-IA) Over Time | Week 2 | -0.65 score on a scale | Standard Deviation 0.64 |
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-Question Version (ACQ-7-IA) Over Time | Week 4 | -0.68 score on a scale | Standard Deviation 0.75 |
Secondary
Japan Sub-study: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 64
FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 milliliter per second. FeNO assessment was conducted prior to spirometry and following a fast of ≥1 hour. Baseline was defined as the last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in the current study.
Time frame: Baseline (Day 1) to Week 64
Population: Safety population included all enrolled participants who took at least 1 dose of study treatment in the current study, regardless of the amount of treatment administered. Only participants with data collected are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Placebo-Dupilumab | Japan Sub-study: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 64 | -8.3 parts per billion | Standard Deviation 27.5 |
Secondary
Japan Sub-study: Number of Participants With Any Treatment-Emergent Adverse Events
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. TEAEs were AEs that developed or worsened or became serious during the TEAE period.
Time frame: From first dose of study treatment (Day 1) up to 112 days post last dose of study treatment, approximately 64 weeks
Population: Safety population included all enrolled participants who took at least 1 dose of study treatment in the current study, regardless of the amount of treatment administered.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Placebo-Dupilumab | Japan Sub-study: Number of Participants With Any Treatment-Emergent Adverse Events | 13 Participants |
Secondary
Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time
FVC was defined as volume of air (in liters) that could be forcibly blown out after full inspiration in upright position as measured by spirometer. Spirometry was performed after wash out period of bronchodilators according to their action duration. Baseline was defined as the original baseline of parent study EFC14153.
Time frame: Baseline (Day 1) and Weeks 2, 8, 12, 24, 52 and 64
Population: Safety population included all participants exposed to at least 1 dose or part of a dose of study treatment during current study regardless of amount of treatment administered. Only participants with data collected at the specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Placebo-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 64 | 3.13 percent predicted FVC | Standard Deviation 15.14 |
| Main Study: Placebo-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 2 | 2.98 percent predicted FVC | Standard Deviation 12.91 |
| Main Study: Placebo-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 8 | 2.88 percent predicted FVC | Standard Deviation 12.17 |
| Main Study: Placebo-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 52 | 3.74 percent predicted FVC | Standard Deviation 13.1 |
| Main Study: Placebo-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 12 | 3.23 percent predicted FVC | Standard Deviation 12.49 |
| Main Study: Placebo-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 24 | 3.19 percent predicted FVC | Standard Deviation 13.35 |
| Main Study: Dupilumab-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 52 | 6.43 percent predicted FVC | Standard Deviation 16.4 |
| Main Study: Dupilumab-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 64 | 4.83 percent predicted FVC | Standard Deviation 16.09 |
| Main Study: Dupilumab-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 2 | 5.02 percent predicted FVC | Standard Deviation 16.33 |
| Main Study: Dupilumab-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 8 | 6.64 percent predicted FVC | Standard Deviation 17.42 |
| Main Study: Dupilumab-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 24 | 5.28 percent predicted FVC | Standard Deviation 16.2 |
| Main Study: Dupilumab-Dupilumab | Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time | Week 12 | 5.03 percent predicted FVC | Standard Deviation 16.45 |
Secondary
Main Study: Percent Change From Baseline in Blood Eosinophil Count at Week 64
Blood samples were collected at specified timepoints to assess percent change from baseline in eosinophil count. Baseline was defined as the original baseline of parent study EFC14153.
Time frame: Baseline (Day 1) to Week 64
Population: Safety population included all participants exposed to at least 1 dose or part of a dose of the study treatment during current study regardless of the amount of treatment administered. Only participants with data collected are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Placebo-Dupilumab | Main Study: Percent Change From Baseline in Blood Eosinophil Count at Week 64 | 34.528 percent change | Standard Deviation 207.067 |
| Main Study: Dupilumab-Dupilumab | Main Study: Percent Change From Baseline in Blood Eosinophil Count at Week 64 | 29.769 percent change | Standard Deviation 323.837 |
Secondary
Number of Participants With Anti-Drug Antibodies (ADAs) Against Dupilumab
ADA positive was defined as either treatment-boosted or treatment-emergent response in the ADA assay. Treatment-boosted response was defined as a positive response in the ADA assay post first dose in the current study that was greater than or equal to 4-fold of the baseline titer levels, when baseline results were positive. Treatment-emergent response was defined as a positive response in the ADA assay post first dose in the current study, when baseline results were negative or missing. Baseline (main study): original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in current study.
Time frame: From first dose of study treatment (Day 1) to Week 64
Population: ADA population (main and sub-study) included all the participants in the safety population with at least 1 non-missing ADA result following the first dose of dupilumab in the current study. Only participants with data collected for the specified categories are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study: Placebo-Dupilumab | Number of Participants With Anti-Drug Antibodies (ADAs) Against Dupilumab | Treatment-emergent ADA Response | 10 Participants |
| Main Study: Placebo-Dupilumab | Number of Participants With Anti-Drug Antibodies (ADAs) Against Dupilumab | Treatment-boosted ADA Response | 1 Participants |
| Main Study: Dupilumab-Dupilumab | Number of Participants With Anti-Drug Antibodies (ADAs) Against Dupilumab | Treatment-emergent ADA Response | 7 Participants |
| Main Study: Dupilumab-Dupilumab | Number of Participants With Anti-Drug Antibodies (ADAs) Against Dupilumab | Treatment-boosted ADA Response | 0 Participants |
| Japan Sub-study: Dupilumab | Number of Participants With Anti-Drug Antibodies (ADAs) Against Dupilumab | Treatment-emergent ADA Response | 2 Participants |
Secondary
Percent Change From Baseline in Total Immunoglobulin (Ig) E in Serum at Week 64
Blood samples were collected at specified timepoints to assess percent change from baseline in total IgE in serum. Baseline (main study): the original baseline of parent study EFC14153. Baseline (sub-study): last available measurement prior to first study treatment dose if participant was treated, or last available value up to enrollment if participant was not exposed to study treatment in current study.
Time frame: Baseline (Day 1) to Week 64
Population: Main study: safety population included all participants exposed to at least 1 dose or part of a dose of the study treatment during current study regardless of the amount of treatment administered. Sub-study: safety population included all enrolled participants who took at least 1 dose of study treatment in the current study, regardless of the amount of treatment administered. Only participants with data collected are reported.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Main Study: Placebo-Dupilumab | Percent Change From Baseline in Total Immunoglobulin (Ig) E in Serum at Week 64 | -76.9 percent change | Inter-Quartile Range -85.2 |
| Main Study: Dupilumab-Dupilumab | Percent Change From Baseline in Total Immunoglobulin (Ig) E in Serum at Week 64 | -86.8 percent change | Inter-Quartile Range -91.4 |
| Japan Sub-study: Dupilumab | Percent Change From Baseline in Total Immunoglobulin (Ig) E in Serum at Week 64 | -75.0 percent change | Inter-Quartile Range -81.1 |
Secondary
Serum Concentrations of Dupilumab
Blood samples were collected at the specified timepoints for determination of functional dupilumab concentration in serum.
Time frame: Weeks 12, 24, 52 and 64
Population: Pharmacokinetic population:participants in safety population with atleast 1 nonmissing;evaluable predose serum concentration post 1st dose of dupilumab in current study.Only participants with data collected at specified timepoints are reported.As prespecified in SAP,serum concentration is presented by dose regimen.Main study:dose regimen was adjusted per participant's weight during study,hence some participants may be counted in more than 1 dose regimen across different weeks based on weight.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Placebo-Dupilumab | Serum Concentrations of Dupilumab | Week 24 | 64201.03 nanogram per milliliter | Standard Deviation 22890.02 |
| Main Study: Placebo-Dupilumab | Serum Concentrations of Dupilumab | Week 64 | 1884.04 nanogram per milliliter | Standard Deviation 9763.01 |
| Main Study: Placebo-Dupilumab | Serum Concentrations of Dupilumab | Week 52 | 52808.85 nanogram per milliliter | Standard Deviation 21526.05 |
| Main Study: Placebo-Dupilumab | Serum Concentrations of Dupilumab | Week 12 | 60740.38 nanogram per milliliter | Standard Deviation 23885.77 |
| Main Study: Dupilumab-Dupilumab | Serum Concentrations of Dupilumab | Week 12 | 80450.15 nanogram per milliliter | Standard Deviation 39865.24 |
| Main Study: Dupilumab-Dupilumab | Serum Concentrations of Dupilumab | Week 52 | 71910.74 nanogram per milliliter | Standard Deviation 42290.54 |
| Main Study: Dupilumab-Dupilumab | Serum Concentrations of Dupilumab | Week 24 | 81849.66 nanogram per milliliter | Standard Deviation 42824.93 |
| Main Study: Dupilumab-Dupilumab | Serum Concentrations of Dupilumab | Week 64 | 3391.86 nanogram per milliliter | Standard Deviation 16196.36 |
| Japan Sub-study: Dupilumab | Serum Concentrations of Dupilumab | Week 52 | 81289.94 nanogram per milliliter | Standard Deviation 31957.07 |
| Japan Sub-study: Dupilumab | Serum Concentrations of Dupilumab | Week 64 | 184.69 nanogram per milliliter | Standard Deviation 582.75 |
| Japan Sub-study: Dupilumab | Serum Concentrations of Dupilumab | Week 12 | 79600.00 nanogram per milliliter | Standard Deviation 25509.84 |
| Japan Sub-study: Dupilumab | Serum Concentrations of Dupilumab | Week 24 | 80675.00 nanogram per milliliter | Standard Deviation 26921.27 |
| Japan Sub-study: Dupilumab 100 mg q2w | Serum Concentrations of Dupilumab | Week 12 | 38600.00 nanogram per milliliter | Standard Deviation 20850.18 |
| Japan Sub-study: Dupilumab 100 mg q2w | Serum Concentrations of Dupilumab | Week 52 | 41000.00 nanogram per milliliter | Standard Deviation 23157.94 |
| Japan Sub-study: Dupilumab 100 mg q2w | Serum Concentrations of Dupilumab | Week 64 | 39.00 nanogram per milliliter | Standard Deviation 0 |
| Japan Sub-study: Dupilumab 100 mg q2w | Serum Concentrations of Dupilumab | Week 24 | 41300.00 nanogram per milliliter | Standard Deviation 22138.65 |
| Japan Sub-study: Dupilumab 200 mg q2w | Serum Concentrations of Dupilumab | Week 12 | 79128.57 nanogram per milliliter | Standard Deviation 24513.31 |
| Japan Sub-study: Dupilumab 200 mg q2w | Serum Concentrations of Dupilumab | Week 24 | 98316.67 nanogram per milliliter | Standard Deviation 18066.81 |
| Japan Sub-study: Dupilumab 200 mg q2w | Serum Concentrations of Dupilumab | Week 52 | 91128.57 nanogram per milliliter | Standard Deviation 28739.33 |
| Japan Sub-study: Dupilumab 200 mg q2w | Serum Concentrations of Dupilumab | Week 64 | 39.00 nanogram per milliliter | Standard Deviation 0 |
| Japan Sub-study: Dupilumab 300 mg q4w | Serum Concentrations of Dupilumab | Week 24 | 55166.67 nanogram per milliliter | Standard Deviation 14558.96 |
| Japan Sub-study: Dupilumab 300 mg q4w | Serum Concentrations of Dupilumab | Week 12 | 53066.67 nanogram per milliliter | Standard Deviation 18569.96 |
| Japan Sub-study: Dupilumab 300 mg q4w | Serum Concentrations of Dupilumab | Week 64 | 39.00 nanogram per milliliter | Standard Deviation 0 |
| Japan Sub-study: Dupilumab 300 mg q4w | Serum Concentrations of Dupilumab | Week 52 | 59300.00 nanogram per milliliter | Standard Deviation 18107.46 |