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 NCT03930732)

Last Updated: 2024-02-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

939 participants

Primary outcome timeframe

Baseline (Day 1) to Week 52

Results posted on

2024-02-28

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to dupilumab 300 mg as subcutaneous (SC) injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, end of treatment \[EOT\] visit occurred 2 weeks after last administration of treatment i.e., at Week 52).	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).
Overall Study STARTED	471	468
Overall Study Safety Population	470	469
Overall Study COMPLETED	434	440
Overall Study NOT COMPLETED	37	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to dupilumab 300 mg as subcutaneous (SC) injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, end of treatment \[EOT\] visit occurred 2 weeks after last administration of treatment i.e., at Week 52).	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).
Overall Study Adverse Event	9	7
Overall Study Poor compliance to protocol	0	1
Overall Study Withdrawal by Subject	23	11
Overall Study Other reason related to Coronavirus Disease-2019 (COVID-19)	0	1
Overall Study Other reason not related to COVID-19	5	8

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=471 Participants 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).	Dupilumab 300 mg q2w n=468 Participants 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).	Total n=939 Participants Total of all reporting groups
Age, Continuous	65.2 years STANDARD_DEVIATION 8.1 • n=5 Participants	65.0 years STANDARD_DEVIATION 8.0 • n=7 Participants	65.1 years STANDARD_DEVIATION 8.1 • n=5 Participants
Sex: Female, Male Female	149 Participants n=5 Participants	170 Participants n=7 Participants	319 Participants n=5 Participants
Sex: Female, Male Male	322 Participants n=5 Participants	298 Participants n=7 Participants	620 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Asian	67 Participants n=5 Participants	67 Participants n=7 Participants	134 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	397 Participants n=5 Participants	393 Participants n=7 Participants	790 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=471 Participants 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).	Dupilumab 300 mg q2w n=468 Participants 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).
Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-Week Treatment Period	1.01 exacerbation per participant-year Interval 0.931 to 1.301	0.776 exacerbation per participant-year Interval 0.645 to 0.934

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=469 Participants 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).	Dupilumab 300 mg q2w n=466 Participants 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).
Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) at Week 12	0.077 liters Standard Error 0.018	0.160 liters Standard Error 0.018

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=469 Participants 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).	Dupilumab 300 mg q2w n=466 Participants 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).
Change From Baseline in Pre-BD FEV1 at Week 52	0.070 liters Standard Error 0.019	0.153 liters Standard Error 0.019

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=186 Participants 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).	Dupilumab 300 mg q2w n=193 Participants 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).
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	0.232 liters Standard Error 0.034

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=186 Participants 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).	Dupilumab 300 mg q2w n=193 Participants 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).
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	0.247 liters Standard Error 0.036

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=456 Participants 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).	Dupilumab 300 mg q2w n=456 Participants 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).
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	-9.732 score on a scale Standard Error 0.810

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 52

Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization.

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.

Outcome measures

Outcome measures
Measure	Placebo n=471 Participants 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).	Dupilumab 300 mg q2w n=468 Participants 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).
Percentage of Participants With SGRQ Improvement >=4 Points at Week 52	43.1 percentage of participants	51.5 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=467 Participants 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).	Dupilumab 300 mg q2w n=461 Participants 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).
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	-2.694 score on a scale Standard Error 0.257

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 52

Population: The subgroup of participants with baseline FeNO \>=20 ppb within the ITT population were included.

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.

Outcome measures

Outcome measures
Measure	Placebo n=188 Participants 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).	Dupilumab 300 mg q2w n=195 Participants 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).
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 Interval 0.831 to 1.502	0.699 exacerbation per participant-year Interval 0.51 to 0.958

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=469 Participants 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).	Dupilumab 300 mg q2w n=466 Participants 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).
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	0.159 liters Standard Error 0.017
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	0.163 liters Standard Error 0.017
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	0.149 liters Standard Error 0.017
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	0.170 liters Standard Error 0.018
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	0.155 liters Standard Error 0.018
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	0.176 liters Standard Error 0.019

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=469 Participants 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).	Dupilumab 300 mg q2w n=467 Participants 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).
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	0.158 liters Standard Error 0.017
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	0.158 liters Standard Error 0.017
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	0.153 liters Standard Error 0.018
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	0.156 liters Standard Error 0.018
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	0.169 liters Standard Error 0.019
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	0.155 liters Standard Error 0.019
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	0.138 liters Standard Error 0.019

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=469 Participants 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).	Dupilumab 300 mg q2w n=466 Participants 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).
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	0.110 liters/second Standard Error 0.016
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	0.115 liters/second Standard Error 0.015
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	0.114 liters/second Standard Error 0.016
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	0.137 liters/second Standard Error 0.016
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	0.142 liters/second Standard Error 0.017
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	0.132 liters/second Standard Error 0.017
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	0.162 liters/second Standard Error 0.017
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	0.135 liters/second Standard Error 0.017

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=469 Participants 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).	Dupilumab 300 mg q2w n=467 Participants 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).
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	0.135 liters/second Standard Error 0.017
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	0.144 liters/second Standard Error 0.017
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	0.144 liters/second Standard Error 0.017
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	0.161 liters/second Standard Error 0.018
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	0.169 liters/second Standard Error 0.019
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	0.161 liters/second Standard Error 0.018
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	0.153 liters/second Standard Error 0.019

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 52

Population: The ITT population consisted of the randomized population analyzed according to the treatment group allocated by randomization.

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.

Outcome measures

Outcome measures
Measure	Placebo n=471 Participants 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).	Dupilumab 300 mg q2w n=468 Participants 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).
Annualized Rate of Severe COPD Exacerbations Over the 52-Week Treatment Period	0.086 exacerbation per participant-year Interval 0.05 to 0.147	0.072 exacerbation per participant-year Interval 0.04 to 0.132

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=471 Participants 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).	Dupilumab 300 mg q2w n=468 Participants 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).
Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period Up to Week 12	0.019 weeks Interval 0.009 to 0.035	0.024 weeks Interval 0.013 to 0.041
Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period Up to Week 24	0.039 weeks Interval 0.024 to 0.059	0.034 weeks Interval 0.021 to 0.054
Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period Up to Week 36	0.045 weeks Interval 0.029 to 0.067	0.039 weeks Interval 0.024 to 0.059
Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period Up to Week 52	0.061 weeks Interval 0.042 to 0.086	0.043 weeks Interval 0.027 to 0.065

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=470 Participants 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).	Dupilumab 300 mg q2w n=469 Participants 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).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) Any TEAE	359 Participants	365 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) Any TESAE	74 Participants	65 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=453 Participants 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).	Dupilumab 300 mg q2w n=462 Participants 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).
Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab Low titer	7 Participants	27 Participants
Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab Moderate titer	0 Participants	1 Participants
Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab High titer	0 Participants	2 Participants

Adverse Events

Placebo

Serious events: 74 serious events

Other events: 172 other events

Deaths: 9 deaths

Dupilumab 300 mg q2w

Serious events: 65 serious events

Other events: 168 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=470 participants at risk 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).	Dupilumab 300 mg q2w n=469 participants at risk 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).
Infections and infestations Nasopharyngitis	9.6% 45/470 • Number of events 60 • 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 Analysis was performed on the Safety population. 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.	9.6% 45/469 • Number of events 55 • 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 Analysis was performed on the Safety population. 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.
Infections and infestations Upper Respiratory Tract Infection	9.8% 46/470 • Number of events 66 • 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 Analysis was performed on the Safety population. 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.	7.9% 37/469 • Number of events 49 • 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 Analysis was performed on the Safety population. 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.
Nervous system disorders Headache	7.0% 33/470 • Number of events 39 • 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 Analysis was performed on the Safety population. 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.	8.1% 38/469 • Number of events 57 • 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 Analysis was performed on the Safety population. 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.
Vascular disorders Hypertension	6.0% 28/470 • Number of events 32 • 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 Analysis was performed on the Safety population. 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.	3.6% 17/469 • Number of events 17 • 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 Analysis was performed on the Safety population. 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.
Gastrointestinal disorders Diarrhoea	3.6% 17/470 • Number of events 18 • 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 Analysis was performed on the Safety population. 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.	5.3% 25/469 • Number of events 34 • 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 Analysis was performed on the Safety population. 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.
Musculoskeletal and connective tissue disorders Back Pain	3.4% 16/470 • Number of events 17 • 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 Analysis was performed on the Safety population. 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.	5.3% 25/469 • Number of events 27 • 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 Analysis was performed on the Safety population. 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.
Injury, poisoning and procedural complications Accidental Overdose	6.4% 30/470 • Number of events 36 • 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 Analysis was performed on the Safety population. 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.	5.5% 26/469 • Number of events 28 • 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 Analysis was performed on the Safety population. 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.

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place