Trial Outcomes & Findings for Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate to Severe COPD With Type 2 Inflammation (NCT NCT04456673)

Last Updated: 2025-05-29

Results Overview

Moderate exacerbations were recorded by the Investigator and defined as acute exacerbation of COPD (AECOPD) event 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 event that required hospitalization or observation for \>24 hours in an emergency department/urgent care facility or resulted 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 events that occurred during the 52-week treatment period divided by the total number of participant-years followed in the 52-week treatment period.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

935 participants

Primary outcome timeframe

Baseline (Day 1) to Week 52

Results posted on

2025-05-29

Participant Flow

The study was conducted at 329 centers in 29 countries. A total of 2769 participants were screened between 06 July 2020 to 19 April 2023, of which 1834 participants were screen failures. Screen failures were mainly due to not meeting the eligibility criteria.

A total of 935 participants were randomized in a 1:1 ratio to receive either dupilumab 300 milligrams (mg) every 2 weeks (q2w) or matching placebo. Randomization was stratified by country, inhaled corticosteroid (ICS) dose (high-dose ICS \[yes/no\]) at baseline, and smoking status at screening (current smokers or not).

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to dupilumab 300 mg subcutaneous (SC) injection q2w up to 52 weeks.	Dupilumab 300 mg q2w Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Overall Study STARTED	465	470
Overall Study Randomized and Treated	465	468
Overall Study Safety Population	464	469
Overall Study COMPLETED	422	428
Overall Study NOT COMPLETED	43	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to dupilumab 300 mg subcutaneous (SC) injection q2w up to 52 weeks.	Dupilumab 300 mg q2w Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Overall Study Adverse Event	7	14
Overall Study Poor compliance to protocol	1	0
Overall Study Withdrawal by Subject	31	23
Overall Study Not related to Coronavirus Disease-2019 (COVID-19)	4	5

Baseline Characteristics

Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate to Severe COPD With Type 2 Inflammation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=465 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=470 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.	Total n=935 Participants Total of all reporting groups
Age, Continuous	64.9 Years STANDARD_DEVIATION 8.5 • n=5 Participants	65.2 Years STANDARD_DEVIATION 8.1 • n=7 Participants	65.0 Years STANDARD_DEVIATION 8.3 • n=5 Participants
Sex: Female, Male Female	153 Participants n=5 Participants	150 Participants n=7 Participants	303 Participants n=5 Participants
Sex: Female, Male Male	312 Participants n=5 Participants	320 Participants n=7 Participants	632 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	26 Participants n=5 Participants	22 Participants n=7 Participants	48 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	416 Participants n=5 Participants	422 Participants n=7 Participants	838 Participants n=5 Participants
Race (NIH/OMB) More than one race	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 52

Population: The Intent-to-treat (ITT) population included all randomized participants analyzed according to the treatment group allocated by randomization.

Outcome measures

Outcome measures
Measure	Placebo n=465 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=470 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-week Treatment Period	1.295 Exacerbation per participant-year Interval 1.048 to 1.6	0.859 Exacerbation per participant-year Interval 0.699 to 1.057

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: The ITT population included all randomized participants analyzed according to the treatment group allocated by randomization. Only those participants with data collected are reported.

The FEV1 was defined as 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. Baseline was defined as the last available value up to randomization but prior to the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=464 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) to Week 12	0.057 Liters Standard Error 0.017	0.139 Liters Standard Error 0.017

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

Population: The ITT population with an opportunity to reach Week 52 included participants who had an opportunity to reach Week 52 assessments and were analyzed for the continuous and proportion type endpoints at Week 52. Only those participants with data collected are reported.

The SGRQ is 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 (respiratory symptoms: frequency and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). Each question's response had a unique empirically derived weight where lowest possible weight was 0 and the highest was 100. Total score was obtained by summing all positive responses in the questionnaire. The total score and domain score was derived from the relevant items and converted to a score of 0 to 100 with a higher score indicating worse health status/health related quality of life. Baseline was defined as the last available value up to randomization but prior to the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=342 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=350 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score to Week 52	-6.444 score on a scale Standard Error 0.922	-9.816 score on a scale Standard Error 0.920

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

A responder was defined as a participant with improvement from baseline in SGRQ total score at Week 52 by ≥4 points. Percentage of participants who achieved a clinically meaningful response in SGRQ total score (improvement by ≥4 points)/responders are reported. SGRQ is a 50-item self-administered questionnaire. Scores by dimension were calculated for 3 domains: symptoms (respiratory symptoms: frequency and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). Each question's response had unique empirically derived weight where lowest possible weight was 0 and highest was 100. Total score was obtained by summing all positive responses in questionnaire. Total score and domain score was derived from relevant items and converted to a score of 0 to 100; higher score indicating worse health status/health related quality of life.

Outcome measures

Outcome measures
Measure	Placebo n=359 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=362 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Percentage of Participants With Saint George's Respiratory Questionnaire Improvement ≥4 Points at Week 52	46.5 Percentage of participants	51.4 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

Outcome measures

Outcome measures
Measure	Placebo n=356 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=359 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second to Week 52	0.054 Liters Standard Error 0.020	0.115 Liters Standard Error 0.021

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 2, 4, 8, 24, 36 and 44

Population: The ITT population with an opportunity to reach Week 52 included participants who had an opportunity to reach Week 52 assessments and were analyzed for all weeks up to Week 52. Only those participants with data collected at specified timepoints are reported.

Outcome measures

Outcome measures
Measure	Placebo n=356 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=359 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 24, 36, and 44 Week 2	0.072 Liters Standard Error 0.018	0.108 Liters Standard Error 0.018
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 24, 36, and 44 Week 4	0.077 Liters Standard Error 0.018	0.132 Liters Standard Error 0.019
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 24, 36, and 44 Week 8	0.069 Liters Standard Error 0.019	0.133 Liters Standard Error 0.020
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 24, 36, and 44 Week 24	0.064 Liters Standard Error 0.020	0.154 Liters Standard Error 0.021
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 24, 36, and 44 Week 36	0.068 Liters Standard Error 0.021	0.117 Liters Standard Error 0.021
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 24, 36, and 44 Week 44	0.065 Liters Standard Error 0.020	0.154 Liters Standard Error 0.021

SECONDARY outcome

Timeframe: Baseline (Day 1) and 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-bronchodilator FEV1 referred to the spirometry performed consistent with the mechanism of action of reliever (30 minutes for albuterol or another short-acting beta agonists). Baseline was defined as the last available value up to randomization but prior to the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=356 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=358 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 12, 24, 36, and 52 Week 2	0.082 Liters Standard Error 0.018	0.101 Liters Standard Error 0.018
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 12, 24, 36, and 52 Week 4	0.098 Liters Standard Error 0.018	0.126 Liters Standard Error 0.018
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 12, 24, 36, and 52 Week 8	0.083 Liters Standard Error 0.019	0.147 Liters Standard Error 0.020
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 12, 24, 36, and 52 Week 12	0.064 Liters Standard Error 0.020	0.136 Liters Standard Error 0.020
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 12, 24, 36, and 52 Week 24	0.081 Liters Standard Error 0.020	0.152 Liters Standard Error 0.020
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 12, 24, 36, and 52 Week 36	0.070 Liters Standard Error 0.020	0.131 Liters Standard Error 0.021
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 12, 24, 36, and 52 Week 52	0.059 Liters Standard Error 0.020	0.127 Liters Standard Error 0.021

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, 44 and 52

FEF is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the FEF at 25% to 75% of forced vital capacity (FVC), where FVC was defined as the volume of air 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. Baseline was defined as the last available value up to randomization but prior to the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=356 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=359 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Change From Baseline in Forced Expiratory Flow (FEF) 25 to 75 Percent (%) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 Week 2	0.057 Liters per second Standard Error 0.018	0.103 Liters per second Standard Error 0.018
Change From Baseline in Forced Expiratory Flow (FEF) 25 to 75 Percent (%) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 Week 4	0.056 Liters per second Standard Error 0.018	0.114 Liters per second Standard Error 0.018
Change From Baseline in Forced Expiratory Flow (FEF) 25 to 75 Percent (%) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 Week 8	0.059 Liters per second Standard Error 0.019	0.134 Liters per second Standard Error 0.019
Change From Baseline in Forced Expiratory Flow (FEF) 25 to 75 Percent (%) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 Week 12	0.066 Liters per second Standard Error 0.021	0.137 Liters per second Standard Error 0.021
Change From Baseline in Forced Expiratory Flow (FEF) 25 to 75 Percent (%) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 Week 24	0.051 Liters per second Standard Error 0.019	0.147 Liters per second Standard Error 0.020
Change From Baseline in Forced Expiratory Flow (FEF) 25 to 75 Percent (%) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 Week 36	0.073 Liters per second Standard Error 0.021	0.128 Liters per second Standard Error 0.022
Change From Baseline in Forced Expiratory Flow (FEF) 25 to 75 Percent (%) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 Week 44	0.053 Liters per second Standard Error 0.021	0.154 Liters per second Standard Error 0.021
Change From Baseline in Forced Expiratory Flow (FEF) 25 to 75 Percent (%) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 Week 52	0.065 Liters per second Standard Error 0.020	0.122 Liters per second Standard Error 0.020

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 52

Population: The ITT population included all randomized participants analyzed according to the treatment group allocated by randomization.

Severe exacerbations were recorded by the Investigator and defined as AECOPD event that required hospitalization or observation for \>24 hours in an emergency department/urgent care facility or resulted 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 events that occurred during the 52-week treatment period divided by the total number of participant-years followed in the 52-week treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=465 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=470 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Annualized Rate of Severe Chronic Obstructive Pulmonary Disease Exacerbations Over the 52-week Treatment Period	0.124 Exacerbation per participant-year Interval 0.072 to 0.215	0.070 Exacerbation per participant-year Interval 0.039 to 0.123

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to Weeks 12, 24, 36 and 52

Population: The ITT population included all randomized participants analyzed according to the treatment group allocated by randomization.

The time to first moderate or severe exacerbation was defined as date of the first event minus randomization date +1. Moderate exacerbations were recorded by the Investigator and defined as AECOPD event that required either systemic corticosteroids (such as intramuscular, intravenous, or oral) and/or antibiotics. Severe exacerbations were recorded by the Investigator and defined as AECOPD event that required hospitalization or observation for \>24 hours in an emergency department/urgent care facility or resulted in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Median time as well as 95% confidence interval was calculated using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Placebo n=465 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=470 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease Exacerbation Event During the 52-week Treatment Period Week 12	0.172 Weeks Interval 0.139 to 0.207	0.108 Weeks Interval 0.081 to 0.138
Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease Exacerbation Event During the 52-week Treatment Period Week 24	0.265 Weeks Interval 0.225 to 0.306	0.206 Weeks Interval 0.17 to 0.244
Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease Exacerbation Event During the 52-week Treatment Period Week 36	0.342 Weeks Interval 0.298 to 0.387	0.292 Weeks Interval 0.25 to 0.335
Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease Exacerbation Event During the 52-week Treatment Period Week 52	0.424 Weeks Interval 0.375 to 0.471	0.361 Weeks Interval 0.315 to 0.407

SECONDARY outcome

Timeframe: From the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days

Population: The Safety population included 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. 1 participant was exposed to different treatment other than planned (was allocated to placebo arm but inadvertently received dupilumab 300 mg q2w on Day 113). The actual arm was considered as dupilumab 300 mg q2w. In safety analyses, the actual arms are used.

An AE was defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was 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 disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed or worsened or became serious during TE period (between the first administration of study treatment to the last administration of the study treatment + 98 days).

Outcome measures

Outcome measures
Measure	Placebo n=464 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=469 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) Any TEAE	330 Participants	322 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) Any TESAE	79 Participants	65 Participants

SECONDARY outcome

Timeframe: From the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days

Blood samples were collected to determine PCSA in hematology. PCSA values were defined as abnormal values considered medically important by the Sponsor according to pre-defined criteria/thresholds based on literature review and defined by the Sponsor for clinical laboratory tests. Criteria for PCSA: Hemoglobin (Hb): ≤115 grams per liter (g/L) (Male\[M\]); ≤95 g/L (Female\[F\]), ≥185 g/L (M); ≥165 g/L (F), Decrease from baseline ≥20 g/L; Hematocrit: ≤0.37 volume per volume (v/v) (M); ≤0.32 v/v (F), ≥0.55 v/v (M); ≥0.5 v/v (F); Erythrocyte Count: ≥6 Tera/L; Platelet count: \<100 Giga/L, ≥700 Giga/L; Leukocytes: \<3 Giga/L (Non-Black \[NB\]); \<2 Giga/L (Black \[B\]), ≥16 Giga/L; Neutrophils: \<1.5 Giga/L (NB); \<1 Giga/L (B); Lymphocytes: \>4 Giga/L; Monocytes: \>0.7 Giga/L; Basophils: \>0.1 Giga/L; Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN ≥0.5 Giga/L).

Outcome measures

Outcome measures
Measure	Placebo n=459 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=464 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Hematocrit: ≥0.55 v/v (M); ≥0.5 v/v (F)	23.1 Percentage of participants	26.5 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Erythrocyte Count: ≥6 Tera/L	4.4 Percentage of participants	6.0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Hb: ≤115 g/ L (M); ≤95 g/ L (F)	6.1 Percentage of participants	5.0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Hb: ≥185 g/L (M); ≥165 g/L (F)	3.7 Percentage of participants	4.7 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Hb: Decrease from baseline ≥20 g/L	9.8 Percentage of participants	11.4 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Hematocrit: ≤0.37 v/v (M); ≤0.32 v/v (F)	6.1 Percentage of participants	5.0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Platelet count: <100 Giga/L	0.2 Percentage of participants	0.6 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Platelet count: ≥700 Giga/L	0.7 Percentage of participants	0.4 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Leukocytes: <3 Giga/L (NB); <2 Giga/L (B)	0.7 Percentage of participants	0.6 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Leukocytes: ≥16 Giga/L	5.2 Percentage of participants	4.1 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Neutrophils: <1.5 Giga/L (NB); <1 Giga/L (B)	2.7 Percentage of participants	1.5 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Lymphocytes: >4 Giga/L	5.9 Percentage of participants	8.2 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Monocytes: >0.7 Giga/L	65.8 Percentage of participants	64.9 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Basophils: >0.1 Giga/L	28.1 Percentage of participants	29.5 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Eosinophils: >0.5 Giga/L or >ULN	15.3 Percentage of participants	21.1 Percentage of participants

SECONDARY outcome

Timeframe: From the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days

Blood samples were collected to determine PCSA in chemistry. PCSA criteria: Sodium: ≤129 millimoles (mmol)/L, ≥160 mmol/L; Potassium: \<3 mmol/L, ≥5.5 mmol/L; Chloride: \<80 mmol/L, \>115 mmol/L; Glucose: ≤3.9 mmol/L and \<lower limit of normal (LLN), ≥11.1 mmol/L (unfasted); ≥7 mmol/L (fasted);Total cholesterol: ≥7.74 mmol/L; Creatinine kinase: \>3 ULN, \>10 ULN; Creatinine: ≥150 micromoles (µmol)/L (adults), ≥30% change from baseline, ≥100% change from baseline, Creatinine Clearance (CG): ≥60 - \<90 milliliter per minute (mL/min), ≥30 - \<60 mL/min, ≥15 - \<30 mL/min, \<15 mL/min; Urea nitrogen: ≥17 mmol/L; Uric acid: \<120 μmol/L, \>408 μmol/L; Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST): \>3 ULN, \>5 ULN, \>10 ULN; Alkaline phosphatase (ALP): \>1.5 ULN; Total bilirubin (TB): \>1.5 ULN, \>2 ULN; ALT and TB: ALT \>3 ULN and Bilirubin \> 2 ULN; Direct bilirubin (DB) and TB: DB \>35% Bilirubin and Bilirubin \>1.5 ULN; Albumin: ≤25 g/L.

Outcome measures

Outcome measures
Measure	Placebo n=459 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=464 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Sodium: ≤129 mmol/L	1.7 Percentage of participants	1.9 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Sodium: ≥160 mmol/L	0 Percentage of participants	0.2 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Potassium: <3 mmol/L	0.4 Percentage of participants	0.4 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Potassium: ≥5.5 mmol/L	11.3 Percentage of participants	10.8 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Chloride: <80 mmol/L	0 Percentage of participants	0.2 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Chloride: >115 mmol/L	0 Percentage of participants	0.2 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Glucose: ≤3.9 mmol/L and <LLN	7.0 Percentage of participants	6.5 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Glucose: ≥11.1 mmol/L (unfasted); ≥7 mmol/L (fasted)	7.6 Percentage of participants	8.8 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Total cholesterol: ≥7.74 mmol/L	6.1 Percentage of participants	4.3 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Creatinine kinase: >3 ULN	2.2 Percentage of participants	3.9 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Creatinine kinase: >10 ULN	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Creatinine: ≥150 µmol/L	2.6 Percentage of participants	3.0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Creatinine: ≥30% change from baseline	20.3 Percentage of participants	19.2 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Creatinine: ≥100% change from baseline	0.7 Percentage of participants	2.4 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry CG: ≥60 - <90 mL/min	36.4 Percentage of participants	39.0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry CG: ≥30 - <60 mL/min	18.5 Percentage of participants	16.8 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry CG: ≥15 - <30 mL/min	0 Percentage of participants	0.9 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry CG: <15 mL/min	0.2 Percentage of participants	0.4 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Urea nitrogen: ≥17 mmol/L	0.2 Percentage of participants	0.4 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Uric acid: <120 μmol/L	0 Percentage of participants	0.4 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Uric acid: >408 μmol/L	37.7 Percentage of participants	39.7 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry ALT: >3 ULN	1.5 Percentage of participants	0.4 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry ALT: >5 ULN	0.2 Percentage of participants	0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry ALT: >10 ULN	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry AST: >3 ULN	0.2 Percentage of participants	0.4 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry AST: >5 ULN	0 Percentage of participants	0.2 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry AST: >10 ULN	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry ALP: >1.5 ULN	3.9 Percentage of participants	2.8 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry TB: >1.5 ULN	0.9 Percentage of participants	2.2 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry TB: >2 ULN	0.2 Percentage of participants	0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry ALT and TB: ALT >3 ULN and Bilirubin > 2 ULN	0.2 Percentage of participants	0 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry DB and TB: DB >35% Bilirubin and Bilirubin >1.5 ULN	4.5 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry Albumin: ≤25 g/L	0.2 Percentage of participants	0.4 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 8, 12, 24, 36, 52 and 64

Urine dipstick samples were collected to determine the significant abnormalities in urine protein.

Outcome measures

Outcome measures
Measure	Placebo n=462 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=469 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Percentage of Participants With Abnormal Results for Urine Protein in Urinalysis Baseline (Day 1)	5.0 Percentage of participants	6.2 Percentage of participants
Percentage of Participants With Abnormal Results for Urine Protein in Urinalysis Week 4	4.1 Percentage of participants	4.9 Percentage of participants
Percentage of Participants With Abnormal Results for Urine Protein in Urinalysis Week 8	3.7 Percentage of participants	5.3 Percentage of participants
Percentage of Participants With Abnormal Results for Urine Protein in Urinalysis Week 12	4.5 Percentage of participants	6.4 Percentage of participants
Percentage of Participants With Abnormal Results for Urine Protein in Urinalysis Week 24	3.9 Percentage of participants	4.5 Percentage of participants
Percentage of Participants With Abnormal Results for Urine Protein in Urinalysis Week 36	3.9 Percentage of participants	4.5 Percentage of participants
Percentage of Participants With Abnormal Results for Urine Protein in Urinalysis Week 52	5.0 Percentage of participants	6.6 Percentage of participants
Percentage of Participants With Abnormal Results for Urine Protein in Urinalysis Week 64	4.5 Percentage of participants	5.5 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: The ADA population included all participants in the safety population who had at least 1 reportable ADA result after first dose of the study treatment.

Plasma samples were collected to evaluate antibodies to dupilumab. Pre-existing immunoreactivity is defined as an ADA positive response in the assay at baseline with all post-treatment ADA results negative, or an ADA positive response at baseline with all post-treatment ADA responses less than 4-fold over baseline titer levels. Treatment-emergent response is defined as a positive response in the ADA assay post first dose, when baseline results are negative or missing. Treatment-boosted response is defined as an ADA positive response in the assay post first dose that is greater-than or equal to 4-fold over baseline titer levels, when baseline results are positive.

Outcome measures

Outcome measures
Measure	Placebo n=452 Participants Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=461 Participants Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab Pre-existing immunoreactivity	6 Participants	4 Participants
Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab Treatment-emergent ADA response	11 Participants	47 Participants
Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab Treatment-boosted ADA response	0 Participants	1 Participants

Adverse Events

Placebo

Serious events: 79 serious events

Other events: 120 other events

Deaths: 8 deaths

Dupilumab 300 mg q2w

Serious events: 65 serious events

Other events: 125 other events

Deaths: 14 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=464 participants at risk Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks.	Dupilumab 300 mg q2w n=469 participants at risk Participants received dupilumab 300 mg SC injection q2w up to 52 weeks.
Infections and infestations Covid-19	7.8% 36/464 • Number of events 38 • AEs, SAEs, all-cause mortality (deaths) were collected from the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days. Analysis was performed on the Safety population. 1 participant was exposed to different treatment other than planned (was allocated to placebo arm but inadvertently received dupilumab 300 mg q2w on Day 113). The actual arm was considered as dupilumab 300 mg q2w. In safety analyses, the actual arms are used.	9.6% 45/469 • Number of events 45 • AEs, SAEs, all-cause mortality (deaths) were collected from the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days. Analysis was performed on the Safety population. 1 participant was exposed to different treatment other than planned (was allocated to placebo arm but inadvertently received dupilumab 300 mg q2w on Day 113). The actual arm was considered as dupilumab 300 mg q2w. In safety analyses, the actual arms are used.
Infections and infestations Nasopharyngitis	6.0% 28/464 • Number of events 31 • AEs, SAEs, all-cause mortality (deaths) were collected from the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days. Analysis was performed on the Safety population. 1 participant was exposed to different treatment other than planned (was allocated to placebo arm but inadvertently received dupilumab 300 mg q2w on Day 113). The actual arm was considered as dupilumab 300 mg q2w. In safety analyses, the actual arms are used.	6.8% 32/469 • Number of events 39 • AEs, SAEs, all-cause mortality (deaths) were collected from the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days. Analysis was performed on the Safety population. 1 participant was exposed to different treatment other than planned (was allocated to placebo arm but inadvertently received dupilumab 300 mg q2w on Day 113). The actual arm was considered as dupilumab 300 mg q2w. In safety analyses, the actual arms are used.
Nervous system disorders Headache	6.2% 29/464 • Number of events 46 • AEs, SAEs, all-cause mortality (deaths) were collected from the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days. Analysis was performed on the Safety population. 1 participant was exposed to different treatment other than planned (was allocated to placebo arm but inadvertently received dupilumab 300 mg q2w on Day 113). The actual arm was considered as dupilumab 300 mg q2w. In safety analyses, the actual arms are used.	7.9% 37/469 • Number of events 72 • AEs, SAEs, all-cause mortality (deaths) were collected from the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days. Analysis was performed on the Safety population. 1 participant was exposed to different treatment other than planned (was allocated to placebo arm but inadvertently received dupilumab 300 mg q2w on Day 113). The actual arm was considered as dupilumab 300 mg q2w. In safety analyses, the actual arms are used.
Injury, poisoning and procedural complications Accidental Overdose	7.1% 33/464 • Number of events 35 • AEs, SAEs, all-cause mortality (deaths) were collected from the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days. Analysis was performed on the Safety population. 1 participant was exposed to different treatment other than planned (was allocated to placebo arm but inadvertently received dupilumab 300 mg q2w on Day 113). The actual arm was considered as dupilumab 300 mg q2w. In safety analyses, the actual arms are used.	6.6% 31/469 • Number of events 34 • AEs, SAEs, all-cause mortality (deaths) were collected from the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days. Analysis was performed on the Safety population. 1 participant was exposed to different treatment other than planned (was allocated to placebo arm but inadvertently received dupilumab 300 mg q2w on Day 113). The actual arm was considered as dupilumab 300 mg q2w. In safety analyses, the actual arms are used.

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610 ext 6#

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER