Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
Primary Objective: To evaluate the efficacy of dupilumab administered every 2 weeks in patients with moderate-or severe Chronic Obstructive Pulmonary Disease (COPD) as measured by * Annualized rate of acute moderate and severe COPD exacerbation (AECOPD) Secondary Objectives: To evaluate the effect of dupilumab administered every 2 weeks on * Pre-bronchodilator forced expiratory volume in 1 second (FEV1) over 12 weeks compared to placebo * Health related quality of life, assessed by the change from baseline to Week 52 in the St. George's Respiratory Questionnaire (SGRQ) * Pre-bronchodilator FEV1 over 52 weeks compared to placebo * Lung function assessments * Moderate and severe COPD exacerbations * To evaluate safety and tolerability * To evaluate dupilumab systemic exposure and incidence of anti-drug antibodies (ADA)
Detailed description
Approximately 68 weeks including a 4-week screening period, a 52-week treatment period, and 12 weeks of follow-up.
Interventions
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation
Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation
Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation
DRUGPlacebo
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants with a physician diagnosis of COPD who met the following criteria at screening: * Current or former smokers with a smoking history of ≥10 pack-years. * Moderate-to-severe COPD (post-bronchodilator FEV1/ forced vital capacity \[FVC\] ratio \<0.70 and post-bronchodilator FEV1 % predicted \>30% and ≤70%). * Medical Research Council (MRC) Dyspnea Scale grade ≥2. * Patient-reported history of signs and symptoms of chronic bronchitis (chronic productive cough) for 3 months in the year up to screening in the absence of other known causes of chronic cough. * Documented history of high exacerbation risk defined as exacerbation history of ≥2 moderate or ≥1 severe within the year prior to inclusion. At least one exacerbation should have occurred while the patient was taking inhaled corticosteroid (ICS)/long acting beta agonist (LABA)/long acting muscarinic antagonist (LAMA) (or LABA/LAMA if ICS is contraindicated). Moderate exacerbations were recorded by the investigator and defined as acute exacerbation of COPD (AECOPD) that required either systemic corticosteroids (intramuscular, intravenous, or oral) and/or antibiotics. One of the two required moderate exacerbations had to require the use of systemic corticosteroids. Severe exacerbations were recorded by the investigator and defined as AECOPD requiring hospitalization or observation \>24 hours in emergency department/urgent care facility. * Background triple therapy (ICS + LABA + LAMA) for 3 months prior to randomization with a stable dose of medication for ≥1 month prior to Visit 1; Double therapy (LABA + LAMA) allowed if ICS was contraindicated. * Evidence of Type 2 inflammation: Patients with blood eosinophils ≥300 cells/microliter at Visit 1.
Exclusion criteria
* COPD diagnosis for less than 12 months prior to randomization. * A current diagnosis of asthma or history of asthma according to the 2018 Global Initiative for Asthma (GINA) guidelines or other accepted guidelines. * Significant pulmonary disease other than COPD (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome etc) or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts. * Cor pulmonale, evidence of right cardiac failure. * Treatment with oxygen of more than 12 hours per day. * Hypercapnia requiring Bi-level ventilation. * AECOPD as defined in inclusion criteria within 4 weeks prior to screening, or during the screening period. * Respiratory tract infection within 4 weeks prior to screening, or during the screening period. * History of, or planned pneumonectomy or lung volume reduction surgery. Patients who were participating in the acute phase of a pulmonary rehabilitation program, ie, who started rehabilitation \<4 weeks prior to screening (Note: patients in the maintenance phase of a rehabilitation program could be included). * Diagnosis of α-1 anti-trypsin deficiency. The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-Week Treatment Period | Baseline (Day 1) to Week 52 | Moderate exacerbations were recorded by the Investigator and defined as acute exacerbation of COPD (AECOPD) that required either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were also recorded by the Investigator and defined as AECOPD requiring hospitalization, or observation for \>24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. Events were adjudicated by independent third party. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pre-BD FEV1 at Week 52 | Baseline (Day 1) to Week 52 | The FEV1 was the volume of air 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. |
| Change From Baseline in Pre-BD FEV1 at Week 12 in Subgroup of Participants With Baseline Fractional Exhaled Nitric Oxide (FeNO) >=20 Parts Per Billion (Ppb) | Baseline (Day 1) to Week 12 | FeNO is a demonstrated biomarker of type 2 airway inflammation in respiratory diseases. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 milliliter per second (mL/s) and reported in ppb. This assessment was conducted prior to spirometry and following a fast of at least 1 hour. |
| Change From Baseline in Pre-BD FEV1 at Week 52 in Subgroup of Participants With Baseline FeNO >=20 Ppb | Baseline (Day 1) to Week 52 | FeNO is a demonstrated biomarker of type 2 airway inflammation in respiratory diseases. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/s and reported in ppb. This assessment was conducted prior to spirometry and following a fast of at least 1 hour. |
| Change From Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 | Baseline (Day 1) to Week 52 | The SGRQ was a 50-item self-administered questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation and rated on electronic diary. Scores by dimension were calculated for 3 domains: symptoms, activity and impacts (psycho-social) as well as a total score. Global and domain scores range from 0 to 100, with 100 representing the worst possible health status and 0 indicating the best possible health status. Higher score indicates worse health status/heath related quality of life. |
| Percentage of Participants With SGRQ Improvement >=4 Points at Week 52 | Baseline (Day 1) to Week 52 | A responder was defined as a participant with improvement from baseline in SGRQ total score at Week 52 by \>=4 points. Participants with improvement \<4 points or with missing values were considered as non-responders. The percentage of participants who achieved a clinically meaningful response in SGRQ total score (reduction \[improvement\] by \>=4 points)/responders are reported. |
| Change From Baseline in Evaluating Respiratory Symptoms (E-RS) in COPD (E-RS: COPD) RS-Total Score at Week 52 | Baseline (Day 1) to Week 52 | The E-RS in COPD scale was a part of the exacerbations of chronic pulmonary disease tool (EXACT). It was a derivative instrument used to measure the effect of treatment on the severity of respiratory symptoms in stable COPD. E-RS: COPD RS-Total Score was derived based on weekly averages of daily assessed 11 respiratory symptom items contained in the 14-item EXACT questionnaire. The RS-Total score represented overall respiratory symptom severity, ranged from 0 to 40. Summation procedure was used to derive the three daily domain scores: 1). RS-Breathlessness (range 0-17), 2) RS-Cough and Sputum (score range 0-11), 3) RS-Chest Symptoms (score range 0-12). The higher the score, more severe were the symptoms. |
| Annualized Rate of Moderate or Severe COPD Exacerbation Over the 52-Week Treatment Period in Subgroup of Participants With Baseline FeNO >=20 Ppb | Baseline (Day 1) to Week 52 | Moderate exacerbations were recorded by the Investigator and defined as AECOPD that required either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were also recorded by the investigator and defined as AECOPD requiring hospitalization, or observation for \>24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate among participants with baseline FeNO \>=20 ppb was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. Events were adjudicated by independent third party. |
| Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) at Week 12 | Baseline (Day 1) to Week 12 | The FEV1 was the volume of air 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. |
| Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36 and 52 | The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Post-BD FEV1 referred to the spirometry performed within 30 minutes after administration of bronchodilator. |
| Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36, 44 and 52 | FEF is the amount of air (in liters) which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Spirometry was performed after a wash out period of bronchodilators according to their action duration. |
| Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36 and 52 | FEF is the amount of air (in liters) which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Spirometry was performed after a wash out period of bronchodilators according to their action duration. |
| Annualized Rate of Severe COPD Exacerbations Over the 52-Week Treatment Period | Baseline (Day 1) to Week 52 | Moderate exacerbations were recorded by the Investigator and defined as AECOPD that required either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were also recorded by the Investigator and defined as AECOPD requiring hospitalization, or observation for \>24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. Events were adjudicated by independent third party. |
| Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period | Baseline (Day 1) and up to Weeks 12, 24, 36 and 52 | The time to first moderate or severe exacerbation was defined as date of the first event minus randomization date +1. The median time to first severe exacerbation was derived from Cox regression model. Moderate exacerbations events were recorded by the investigator and defined as AECOPD that require either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were recorded by the Investigator and defined as AECOPD requiring hospitalization, or observation for \>24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs were collected from the time from the first administration of study treatment to the last administration of the study treatment + 98 days, up to 491 days | An Adverse Event (AE) was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during TE period which was defined as the period from the time of first dose of study treatment until the last visit in the study. Serious adverse events (SAE) were defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. |
| Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab | Up to Week 52 | Number of participants with treatment-emergent response to dupilumab with peak post-baseline titers during the on-treatment period are reported. Treatment-emergent response was defined as a positive response in the ADA assay post first dose, when baseline results were negative or missing. Categories were based on titer values and included: low (Titer \<1000); moderate (1000\<=Titer\<=10,000); and high (Titer \>10,000). On-treatment period was defined as last study treatment administration plus 14 days; that is, Week 52. |
| Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Baseline (Day 1) to Weeks 2, 4, 8, 24, 36 and 44 | The FEV1 was the volume of air 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. |
Countries
Argentina, Bulgaria, Canada, Chile, China, Czechia, Denmark, Finland, Germany, Hungary, Israel, Italy, Japan, Mexico, Poland, Romania, Russia, Slovakia, South Korea, Spain, Sweden, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
The study was conducted at 275 centers in 24 countries. A total of 2599 participants were screened from 15 Apr 2019 to 12 Jan 2022, of which 1660 were screen failures due to not meeting eligibility criteria.
Pre-assignment details
A total of 939 participants were randomized in a 1:1 ratio to receive either dupilumab 300 milligrams (mg) every 2 weeks (q2w) or matching placebo for 52 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to dupilumab 300 mg as SC injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of treatment i.e., at Week 52). | 471 |
| Dupilumab 300 mg q2w Participants received dupilumab 300 mg administered as SC injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of treatment i.e., at Week 52). | 468 |
| Total | 939 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 7 |
| Overall Study | Other reason not related to COVID-19 | 5 | 8 |
| Overall Study | Other reason related to Coronavirus Disease-2019 (COVID-19) | 0 | 1 |
| Overall Study | Poor compliance to protocol | 0 | 1 |
| Overall Study | Withdrawal by Subject | 23 | 11 |
Baseline characteristics
| Characteristic | Dupilumab 300 mg q2w | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 8 | 65.1 years STANDARD_DEVIATION 8.1 | 65.2 years STANDARD_DEVIATION 8.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 67 Participants | 134 Participants | 67 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 393 Participants | 790 Participants | 397 Participants |
| Sex: Female, Male Female | 170 Participants | 319 Participants | 149 Participants |
| Sex: Female, Male Male | 298 Participants | 620 Participants | 322 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 470 | 8 / 469 |
| other Total, other adverse events | 172 / 470 | 168 / 469 |
| serious Total, serious adverse events | 74 / 470 | 65 / 469 |
Outcome results
Primary
Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-Week Treatment Period
Moderate exacerbations were recorded by the Investigator and defined as acute exacerbation of COPD (AECOPD) that required either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were also recorded by the Investigator and defined as AECOPD requiring hospitalization, or observation for \>24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. Events were adjudicated by independent third party.
Time frame: Baseline (Day 1) to Week 52
Population: The intent-to-treat (ITT) population consisted of the randomized population analyzed according to the treatment group allocated by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-Week Treatment Period | 1.01 exacerbation per participant-year |
| Dupilumab 300 mg q2w | Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-Week Treatment Period | 0.776 exacerbation per participant-year |
Comparison: Derived using negative binomial model with the total number of the events occurring during the 52-week treatment period as the response variable, and treatment group, region (pooled country), inhaled corticosteroid (ICS) dose, smoking status at screening, baseline disease severity, and number of moderate or severe COPD exacerbation events within one year prior to the study as covariates, and log-transformed treatment duration as an offset variable.p-value: 0.000595% CI: [-0.508, -0.14]Negative binomial model
Secondary
Annualized Rate of Moderate or Severe COPD Exacerbation Over the 52-Week Treatment Period in Subgroup of Participants With Baseline FeNO >=20 Ppb
Moderate exacerbations were recorded by the Investigator and defined as AECOPD that required either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were also recorded by the investigator and defined as AECOPD requiring hospitalization, or observation for \>24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate among participants with baseline FeNO \>=20 ppb was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. Events were adjudicated by independent third party.
Time frame: Baseline (Day 1) to Week 52
Population: The subgroup of participants with baseline FeNO \>=20 ppb within the ITT population were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Annualized Rate of Moderate or Severe COPD Exacerbation Over the 52-Week Treatment Period in Subgroup of Participants With Baseline FeNO >=20 Ppb | 1.117 exacerbation per participant-year |
| Dupilumab 300 mg q2w | Annualized Rate of Moderate or Severe COPD Exacerbation Over the 52-Week Treatment Period in Subgroup of Participants With Baseline FeNO >=20 Ppb | 0.699 exacerbation per participant-year |
Comparison: Derived using negative binomial model with the total number of the events occurring during the 52-week treatment period as the response variable, and treatment group, region (pooled country), ICS dose, smoking status at screening, baseline disease severity, and number of moderate or severe COPD exacerbation events within one year prior to the study as covariates, and log-transformed treatment duration as an offset variable.p-value: 0.005295% CI: [-0.728, -0.109]Negative binomial model
Secondary
Annualized Rate of Severe COPD Exacerbations Over the 52-Week Treatment Period
Moderate exacerbations were recorded by the Investigator and defined as AECOPD that required either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were also recorded by the Investigator and defined as AECOPD requiring hospitalization, or observation for \>24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. Events were adjudicated by independent third party.
Time frame: Baseline (Day 1) to Week 52
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Annualized Rate of Severe COPD Exacerbations Over the 52-Week Treatment Period | 0.086 exacerbation per participant-year |
| Dupilumab 300 mg q2w | Annualized Rate of Severe COPD Exacerbations Over the 52-Week Treatment Period | 0.072 exacerbation per participant-year |
Secondary
Change From Baseline in Evaluating Respiratory Symptoms (E-RS) in COPD (E-RS: COPD) RS-Total Score at Week 52
The E-RS in COPD scale was a part of the exacerbations of chronic pulmonary disease tool (EXACT). It was a derivative instrument used to measure the effect of treatment on the severity of respiratory symptoms in stable COPD. E-RS: COPD RS-Total Score was derived based on weekly averages of daily assessed 11 respiratory symptom items contained in the 14-item EXACT questionnaire. The RS-Total score represented overall respiratory symptom severity, ranged from 0 to 40. Summation procedure was used to derive the three daily domain scores: 1). RS-Breathlessness (range 0-17), 2) RS-Cough and Sputum (score range 0-11), 3) RS-Chest Symptoms (score range 0-12). The higher the score, more severe were the symptoms.
Time frame: Baseline (Day 1) to Week 52
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization. Only those participants with data available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Evaluating Respiratory Symptoms (E-RS) in COPD (E-RS: COPD) RS-Total Score at Week 52 | -1.558 score on a scale | Standard Error 0.256 |
| Dupilumab 300 mg q2w | Change From Baseline in Evaluating Respiratory Symptoms (E-RS) in COPD (E-RS: COPD) RS-Total Score at Week 52 | -2.694 score on a scale | Standard Error 0.257 |
Comparison: Derived from MMRM model with the change from baseline in E-RS: COPD RS-Total Score to Week 52 as response variables, and treatment group, region (pooled country), ICS dose, smoking status at screening, visit, treatment-by-visit interaction, baseline E-RS: COPD RS-Total Score, and baseline E-RS: COPD RS-Total Score-by-visit interaction as covariates. Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.001295% CI: [-1.823, -0.45]MMRM model
Secondary
Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52
FEF is the amount of air (in liters) which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Spirometry was performed after a wash out period of bronchodilators according to their action duration.
Time frame: Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36 and 52
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization. Only those participants with data available were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 8 | 0.083 liters/second | Standard Error 0.017 |
| Placebo | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 24 | 0.093 liters/second | Standard Error 0.019 |
| Placebo | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 4 | 0.087 liters/second | Standard Error 0.017 |
| Placebo | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 36 | 0.093 liters/second | Standard Error 0.019 |
| Placebo | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 12 | 0.089 liters/second | Standard Error 0.018 |
| Placebo | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 52 | 0.093 liters/second | Standard Error 0.019 |
| Placebo | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 2 | 0.074 liters/second | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 52 | 0.153 liters/second | Standard Error 0.019 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 2 | 0.135 liters/second | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 4 | 0.144 liters/second | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 8 | 0.144 liters/second | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 12 | 0.161 liters/second | Standard Error 0.018 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 24 | 0.169 liters/second | Standard Error 0.019 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 36 | 0.161 liters/second | Standard Error 0.018 |
Secondary
Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52
The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Post-BD FEV1 referred to the spirometry performed within 30 minutes after administration of bronchodilator.
Time frame: Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36 and 52
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 8 | 0.077 liters | Standard Error 0.018 |
| Placebo | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 24 | 0.072 liters | Standard Error 0.019 |
| Placebo | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 4 | 0.080 liters | Standard Error 0.017 |
| Placebo | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 36 | 0.072 liters | Standard Error 0.019 |
| Placebo | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 12 | 0.084 liters | Standard Error 0.018 |
| Placebo | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 52 | 0.058 liters | Standard Error 0.019 |
| Placebo | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 2 | 0.071 liters | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 52 | 0.138 liters | Standard Error 0.019 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 2 | 0.158 liters | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 4 | 0.158 liters | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 8 | 0.153 liters | Standard Error 0.018 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 12 | 0.156 liters | Standard Error 0.018 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 24 | 0.169 liters | Standard Error 0.019 |
| Dupilumab 300 mg q2w | Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 | Week 36 | 0.155 liters | Standard Error 0.019 |
Secondary
Change From Baseline in Pre-BD FEV1 at Week 12 in Subgroup of Participants With Baseline Fractional Exhaled Nitric Oxide (FeNO) >=20 Parts Per Billion (Ppb)
FeNO is a demonstrated biomarker of type 2 airway inflammation in respiratory diseases. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 milliliter per second (mL/s) and reported in ppb. This assessment was conducted prior to spirometry and following a fast of at least 1 hour.
Time frame: Baseline (Day 1) to Week 12
Population: The subgroup of participants with baseline FeNO \>=20 ppb within the ITT population were included. Only those participants with data available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pre-BD FEV1 at Week 12 in Subgroup of Participants With Baseline Fractional Exhaled Nitric Oxide (FeNO) >=20 Parts Per Billion (Ppb) | 0.108 liters | Standard Error 0.035 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD FEV1 at Week 12 in Subgroup of Participants With Baseline Fractional Exhaled Nitric Oxide (FeNO) >=20 Parts Per Billion (Ppb) | 0.232 liters | Standard Error 0.034 |
Comparison: Derived from MMRM model with the change from baseline in pre-BD FEV1 up to Week 12 as response variables, and treatment group, age, sex, height, region (pooled country), ICS dose, smoking status at screening, visit, treatment-by-visit interaction, baseline pre-BD FEV1, and FEV1 baseline-by-visit interaction as covariates. Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.002295% CI: [0.045, 0.203]MMRM model
Secondary
Change From Baseline in Pre-BD FEV1 at Week 52
The FEV1 was the volume of air 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.
Time frame: Baseline (Day 1) to Week 52
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization. Only those participants with data available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pre-BD FEV1 at Week 52 | 0.070 liters | Standard Error 0.019 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD FEV1 at Week 52 | 0.153 liters | Standard Error 0.019 |
Comparison: Derived from MMRM model with the change from baseline in pre-BDFEV1 up to Week 52 as response variables, and treatment group, age, sex, height, region (pooled country), ICS dose, smoking status at screening, visit, treatment-by-visit interaction, baseline pre-BD FEV1, and FEV1 baseline-by-visit interaction as covariates. Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.000395% CI: [0.038, 0.128]MMRM model
Secondary
Change From Baseline in Pre-BD FEV1 at Week 52 in Subgroup of Participants With Baseline FeNO >=20 Ppb
FeNO is a demonstrated biomarker of type 2 airway inflammation in respiratory diseases. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/s and reported in ppb. This assessment was conducted prior to spirometry and following a fast of at least 1 hour.
Time frame: Baseline (Day 1) to Week 52
Population: The subgroup of participants with baseline FeNO \>=20 ppb within the ITT population were included. Only those participants with data available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pre-BD FEV1 at Week 52 in Subgroup of Participants With Baseline FeNO >=20 Ppb | 0.120 liters | Standard Error 0.037 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD FEV1 at Week 52 in Subgroup of Participants With Baseline FeNO >=20 Ppb | 0.247 liters | Standard Error 0.036 |
Comparison: Derived from MMRM model with the change from baseline in pre-BD FEV1 up to Week 52 as response variables, and treatment group, age, sex, height, region (pooled country), ICS dose, smoking status at screening, visit, treatment-by-visit interaction, baseline pre-BD FEV1, and FEV1 baseline-by-visit interaction as covariates. Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.003495% CI: [0.042, 0.212]MMRM model
Secondary
Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44
The FEV1 was the volume of air 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.
Time frame: Baseline (Day 1) to Weeks 2, 4, 8, 24, 36 and 44
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization. Only those participants with data available were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 2 | 0.075 liters | Standard Error 0.017 |
| Placebo | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 4 | 0.069 liters | Standard Error 0.017 |
| Placebo | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 8 | 0.069 liters | Standard Error 0.017 |
| Placebo | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 24 | 0.068 liters | Standard Error 0.018 |
| Placebo | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 36 | 0.072 liters | Standard Error 0.018 |
| Placebo | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 44 | 0.089 liters | Standard Error 0.019 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 36 | 0.155 liters | Standard Error 0.018 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 2 | 0.159 liters | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 24 | 0.170 liters | Standard Error 0.018 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 4 | 0.163 liters | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 44 | 0.176 liters | Standard Error 0.019 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 | Week 8 | 0.149 liters | Standard Error 0.017 |
Secondary
Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52
FEF is the amount of air (in liters) which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Spirometry was performed after a wash out period of bronchodilators according to their action duration.
Time frame: Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36, 44 and 52
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization. Only those participants with data available were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 2 | 0.065 liters/second | Standard Error 0.016 |
| Placebo | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 4 | 0.066 liters/second | Standard Error 0.015 |
| Placebo | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 8 | 0.069 liters/second | Standard Error 0.016 |
| Placebo | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 12 | 0.076 liters/second | Standard Error 0.016 |
| Placebo | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 24 | 0.080 liters/second | Standard Error 0.017 |
| Placebo | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 36 | 0.087 liters/second | Standard Error 0.017 |
| Placebo | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 44 | 0.091 liters/second | Standard Error 0.017 |
| Placebo | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 52 | 0.088 liters/second | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 52 | 0.135 liters/second | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 2 | 0.110 liters/second | Standard Error 0.016 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 24 | 0.142 liters/second | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 4 | 0.115 liters/second | Standard Error 0.015 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 44 | 0.162 liters/second | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 8 | 0.114 liters/second | Standard Error 0.016 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 36 | 0.132 liters/second | Standard Error 0.017 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 | Week 12 | 0.137 liters/second | Standard Error 0.016 |
Secondary
Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) at Week 12
The FEV1 was the volume of air 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.
Time frame: Baseline (Day 1) to Week 12
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization. Only those participants with data available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) at Week 12 | 0.077 liters | Standard Error 0.018 |
| Dupilumab 300 mg q2w | Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) at Week 12 | 0.160 liters | Standard Error 0.018 |
Comparison: Derived from mixed-effect model with repeated measures (MMRM) model with the change from baseline in pre-BD FEV1 up to Week 12 as response variables, and treatment group, age, sex, height, region (pooled country), ICS dose, smoking status at screening, visit, treatment-by-visit interaction, baseline pre-BD FEV1, and FEV1 baseline-by-visit interaction as covariates. Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [0.042, 0.125]MMRM model
Secondary
Change From Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) Total Score at Week 52
The SGRQ was a 50-item self-administered questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation and rated on electronic diary. Scores by dimension were calculated for 3 domains: symptoms, activity and impacts (psycho-social) as well as a total score. Global and domain scores range from 0 to 100, with 100 representing the worst possible health status and 0 indicating the best possible health status. Higher score indicates worse health status/heath related quality of life.
Time frame: Baseline (Day 1) to Week 52
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization. Only those participants with data available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 | -6.369 score on a scale | Standard Error 0.816 |
| Dupilumab 300 mg q2w | Change From Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 | -9.732 score on a scale | Standard Error 0.81 |
Comparison: Derived from MMRM model with the change from baseline in SGRQ total score up to Week 52 as response variables, and treatment group, region (pooled country), ICS dose, smoking status at screening, treatment-by-visit interaction, baseline SGRQ total score, and SGRQ baseline-by-visit interaction as covariates. Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.001795% CI: [-5.459, -1.266]MMRM model
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab
Number of participants with treatment-emergent response to dupilumab with peak post-baseline titers during the on-treatment period are reported. Treatment-emergent response was defined as a positive response in the ADA assay post first dose, when baseline results were negative or missing. Categories were based on titer values and included: low (Titer \<1000); moderate (1000\<=Titer\<=10,000); and high (Titer \>10,000). On-treatment period was defined as last study treatment administration plus 14 days; that is, Week 52.
Time frame: Up to Week 52
Population: The ADA population consisted of all participants in the Safety population with at least 1 reportable ADA results (either 'ADA negative' or 'ADA positive') after first dose of the study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab | Low titer | 7 Participants |
| Placebo | Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab | Moderate titer | 0 Participants |
| Placebo | Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab | High titer | 0 Participants |
| Dupilumab 300 mg q2w | Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab | Low titer | 27 Participants |
| Dupilumab 300 mg q2w | Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab | Moderate titer | 1 Participants |
| Dupilumab 300 mg q2w | Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab | High titer | 2 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An Adverse Event (AE) was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during TE period which was defined as the period from the time of first dose of study treatment until the last visit in the study. Serious adverse events (SAE) were defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
Time frame: TEAEs were collected from the time from the first administration of study treatment to the last administration of the study treatment + 98 days, up to 491 days
Population: The Safety population consisted of all participants who actually received at least 1 dose or partial of a dose of the study treatment, analyzed according to the treatment participants actually received. One participant was exposed to different treatment other than planned (was randomized to placebo arm but received dupilumab on Day 40). The actual arm was considered as dupilumab 300 mg q2w. In safety analyses, the actual arms are used.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TEAE | 359 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TESAE | 74 Participants |
| Dupilumab 300 mg q2w | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TEAE | 365 Participants |
| Dupilumab 300 mg q2w | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TESAE | 65 Participants |
Secondary
Percentage of Participants With SGRQ Improvement >=4 Points at Week 52
A responder was defined as a participant with improvement from baseline in SGRQ total score at Week 52 by \>=4 points. Participants with improvement \<4 points or with missing values were considered as non-responders. The percentage of participants who achieved a clinically meaningful response in SGRQ total score (reduction \[improvement\] by \>=4 points)/responders are reported.
Time frame: Baseline (Day 1) to Week 52
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With SGRQ Improvement >=4 Points at Week 52 | 43.1 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With SGRQ Improvement >=4 Points at Week 52 | 51.5 percentage of participants |
Comparison: Derived from logistic regression model which includes treatment group, region (pooled country), ICS dose, smoking status at screening, and baseline SGRQ total score as covariates. Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.008995% CI: [1.096, 1.89]Regression, Logistic
Secondary
Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period
The time to first moderate or severe exacerbation was defined as date of the first event minus randomization date +1. The median time to first severe exacerbation was derived from Cox regression model. Moderate exacerbations events were recorded by the investigator and defined as AECOPD that require either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were recorded by the Investigator and defined as AECOPD requiring hospitalization, or observation for \>24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days.
Time frame: Baseline (Day 1) and up to Weeks 12, 24, 36 and 52
Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period | Up to Week 12 | 0.019 weeks |
| Placebo | Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period | Up to Week 24 | 0.039 weeks |
| Placebo | Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period | Up to Week 36 | 0.045 weeks |
| Placebo | Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period | Up to Week 52 | 0.061 weeks |
| Dupilumab 300 mg q2w | Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period | Up to Week 52 | 0.043 weeks |
| Dupilumab 300 mg q2w | Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period | Up to Week 12 | 0.024 weeks |
| Dupilumab 300 mg q2w | Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period | Up to Week 36 | 0.039 weeks |
| Dupilumab 300 mg q2w | Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period | Up to Week 24 | 0.034 weeks |