Trial Outcomes & Findings for A Phase 4, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study of the Effect of Dupilumab on Sleep Disturbance in Patients With Uncontrolled Persistent Asthma (NCT NCT04502862)

NCT ID: NCT04502862

Last Updated: 2024-12-06

Results Overview

The ASDQ is a participant-reported outcome (PRO) measure designed to assess the impact of asthma on participants' sleep. Participants were instructed to record the severity of the disturbance of their sleep due to asthma as: 0 = slept through the night, no asthma symptoms; 1 = slept well, no night time awakenings because of asthma, but some asthma symptoms in the morning; 2 = woke up once because of asthma (may or may not include early awakening); 3 = woke up several times because of asthma (may or may not include early awakening) and 4 = bad night, awake most of the night because of asthma. The participants recorded their sleep disturbance in an electronic diary, once a day upon awakening. Total scores ranges between 0 to 4 with 0 indicating no impact of asthma on sleep and 4 indicating higher impact of asthma on sleep. Higher scores indicated worse outcomes. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 202 participants
• Primary outcome timeframe: Baseline (Day -6 to Day 1) up to Week 12
• Results posted on: 2024-12-06

Participant Flow

The study was conducted at 52 centers in 11 countries. A total of 397 participants were screened between 10 August 2020 to 30 May 2023, of which 195 participants were screen failures. Screen failures were mainly due to not meeting the eligibility criteria.

A total of 202 participants were randomized in a ratio of 1:1 to receive dupilumab or matching placebo every 2 weeks (Q2W) for 12 weeks.

Participant milestones

Measure	Dupilumab 200 mg Q2W Participants received a loading dose of 400 milligrams (mg) of dupilumab (2 injections × 200 mg) subcutaneous (SC) on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Overall Study STARTED	101	101
Overall Study Randomized and Treated	100	101
Overall Study COMPLETED	95	94
Overall Study NOT COMPLETED	6	7

Reasons for withdrawal

Measure	Dupilumab 200 mg Q2W Participants received a loading dose of 400 milligrams (mg) of dupilumab (2 injections × 200 mg) subcutaneous (SC) on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Overall Study Not Related to Coronavirus Disease-2019 (COVID-19) pandemic	4	6
Overall Study Withdrawal by Subject	1	0
Overall Study Adverse Event	1	1

Baseline Characteristics

Only those participants with data available at baseline are reported.

Baseline characteristics by cohort

Measure	Dupilumab 200 mg Q2W n=101 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=101 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.	Total n=202 Participants Total of all reporting groups
Age, Continuous	46.9 Years STANDARD_DEVIATION 12.63 • n=101 Participants	46.6 Years STANDARD_DEVIATION 12.71 • n=101 Participants	46.7 Years STANDARD_DEVIATION 12.64 • n=202 Participants
Sex: Female, Male Female	68 Participants n=101 Participants	76 Participants n=101 Participants	144 Participants n=202 Participants
Sex: Female, Male Male	33 Participants n=101 Participants	25 Participants n=101 Participants	58 Participants n=202 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=101 Participants	0 Participants n=101 Participants	0 Participants n=202 Participants
Race (NIH/OMB) Asian	4 Participants n=101 Participants	3 Participants n=101 Participants	7 Participants n=202 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=101 Participants	1 Participants n=101 Participants	1 Participants n=202 Participants
Race (NIH/OMB) Black or African American	4 Participants n=101 Participants	4 Participants n=101 Participants	8 Participants n=202 Participants
Race (NIH/OMB) White	92 Participants n=101 Participants	92 Participants n=101 Participants	184 Participants n=202 Participants
Race (NIH/OMB) More than one race	1 Participants n=101 Participants	0 Participants n=101 Participants	1 Participants n=202 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=101 Participants	1 Participants n=101 Participants	1 Participants n=202 Participants
Sleep Disturbance Score	1.89 Score on a scale STANDARD_DEVIATION 0.769 • n=99 Participants • Only those participants with data available at baseline are reported.	1.83 Score on a scale STANDARD_DEVIATION 0.754 • n=98 Participants • Only those participants with data available at baseline are reported.	1.86 Score on a scale STANDARD_DEVIATION 0.760 • n=197 Participants • Only those participants with data available at baseline are reported.

PRIMARY outcome

Timeframe: Baseline (Day -6 to Day 1) up to Week 12

Population: The ITT for primary endpoint (ITTp) analysis set consisted of all ITT participants excluding those who used the original version of sleep disturbance questionnaire at baseline and/or post-baseline included in the mixed effect model for repeated measures (MMRM) model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported.

The ASDQ is a participant-reported outcome (PRO) measure designed to assess the impact of asthma on participants' sleep. Participants were instructed to record the severity of the disturbance of their sleep due to asthma as: 0 = slept through the night, no asthma symptoms; 1 = slept well, no night time awakenings because of asthma, but some asthma symptoms in the morning; 2 = woke up once because of asthma (may or may not include early awakening); 3 = woke up several times because of asthma (may or may not include early awakening) and 4 = bad night, awake most of the night because of asthma. The participants recorded their sleep disturbance in an electronic diary, once a day upon awakening. Total scores ranges between 0 to 4 with 0 indicating no impact of asthma on sleep and 4 indicating higher impact of asthma on sleep. Higher scores indicated worse outcomes. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=94 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=93 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Change From Baseline to Week 12 in Sleep Disturbance Score Using the Asthma Sleep Disturbance Questionnaire (ASDQ)	-0.88 Score on a scale Standard Error 0.077	-0.81 Score on a scale Standard Error 0.077

SECONDARY outcome

Timeframe: Baseline (Day -6 to Day 1) up to Week 12

Population: The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported.

Sleep diary is used to assess adult sleep disturbance due to asthma. Number of nocturnal awakenings was determined based on answer on question from sleep diary: "Approximately how many times did you wake up last night (not including when you woke up for the day today)?" Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=98 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=98 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Change From Baseline to Week 12 on the Number of Nocturnal Awakenings (Sleep Diary)	-0.71 Number of nocturnal awakenings Standard Error 0.080	-0.71 Number of nocturnal awakenings Standard Error 0.080

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Week 12

Population: The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported.

PROMIS sleep-related impairment eight-term 8a scale was administered to assess impact of sleep-related impairment during waking hours. The questionnaire focuses on self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours, and perceived functional impairments during wakefulness associated with sleep problems or impaired alertness. It assesses sleep-related impairment over the past 7 days. Each item is rated on a 5-point scale (1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; and 5 = very much) with a raw score from 8 to 40 with higher scores indicating greater sleep impairment. PROMIS T-score is presented which rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. Possible range for T-score=30 to 80; higher scores=greater severity of sleep impairment. Baseline=last available valid (non-missing) value up to and including the day of first dose of investigational medicinal product (IMP).

Outcome measures

Measure	Dupilumab 200 mg Q2W n=97 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=96 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Change From Baseline to Week 12 in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment 8a Scale	-7.20 T-score Standard Error 0.624	-6.51 T-score Standard Error 0.626

SECONDARY outcome

Timeframe: Baseline (Day -6 to Day 1) up to Week 12

Population: The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported.

Sleep diary is used to assess adult sleep disturbance due to asthma. Sleep quality was assessed on a 11-point scale which ranged from 0 (worst possible sleep) to 10 (best possible sleep); higher scores indicated better outcomes. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=98 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=98 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Change From Baseline to Week 12 in Sleep Quality (Sleep Diary)	1.14 Score on a scale Standard Error 0.151	0.97 Score on a scale Standard Error 0.152

SECONDARY outcome

Timeframe: Baseline (Day -6 to Day 1) up to Week 12

Population: The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported.

Sleep Diary is used to assess adult sleep disturbance due to asthma. Question about restorative sleep asks participants to recall "when they got up for the day today". Restorative sleep was assessed on a 11-point scale which ranged from 0 (worst possible sleep) to 10 (best possible sleep); higher scores indicated better outcomes. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=98 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=98 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Change From Baseline to Week 12 in Restorative Sleep (Sleep Diary)	1.15 Score on a scale Standard Error 0.152	1.02 Score on a scale Standard Error 0.152

SECONDARY outcome

Timeframe: Baseline (Day -6 to Day 1) up to Week 12

Population: The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported.

Sleep Diary is used to assess adult sleep disturbance due to asthma. WASO was calculated as time awake after initial sleep onset but before the final awakening. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=98 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=98 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Change From Baseline to Week 12 in Wake After Sleep Onset (WASO) (Sleep Diary)	-30.58 Minutes Standard Error 3.945	-26.48 Minutes Standard Error 3.962

SECONDARY outcome

Timeframe: Baseline (Day -6 to Day 1) up to Week 12

Population: The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported.

Wrist actigraphy is a procedure that records and integrates occurrence and degree of limb movement activity over an extended recording period. The signals generated by wrist movement are sensed by a tiny microcomputer contained within watch and translated into activity counts. Algorithms have been developed to translate these activity counts or "epochs" (or "periods") that correspond to times when a person is likely to be asleep or wake. Actigraph was worn on wrist of non-dominant hand to provide estimates of duration, timing and patterns of sleep in study participants. After the watch data were scored by a selected expert center, a number of summary measurements were generated for each participant, including WASO. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=84 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=92 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Change From Baseline to Week 12 in WASO Based on Actigraphy Data	-1.64 Minutes Standard Error 2.286	-1.17 Minutes Standard Error 2.215

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1) up to Week 12

Population: The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported.

The ADSD is a PRO measure designed to measure asthma symptoms in adult and adolescent (12 years of age and older) participants diagnosed with mild to severe asthma. ADSD assesses asthma severity based on participant self-report of asthma core symptoms, i.e., difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough. Participants were asked to complete the ADSD every night before they go to bed, thinking about their asthma symptoms today, from when they got up this morning until now. ADSD is composed of 6 items rated using an 11-point NRS that ranges from 0 = None to 10 = as bad as you can imagine. The total score was calculated by averaging all 6 items and therefore the score ranged from 0 to 10. Higher scores indicated worse outcomes. Baseline value was average of the data from Day -7 to Day -1.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=71 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=70 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Change From Baseline to Week 12 in Asthma Daytime Symptom Diary (ADSD)	-1.78 Score on a scale Standard Error 0.192	-1.56 Score on a scale Standard Error 0.193

SECONDARY outcome

Timeframe: Baseline (Day -6 to Day -1) up to Week 12

Population: The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported.

The ANSD is a PRO measure designed to measure asthma symptoms in adult and adolescent (12 years of age and older) participants diagnosed with mild to severe asthma. ANSD assesses asthma severity based on participant self-report of asthma core symptoms, i.e., difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough. Participants were asked to complete the ANSD when getting up, thinking about their asthma symptoms last night from when they went to bed until now. ANSD is composed of 6 items rated using an 11-point NRS that ranges from 0 = None to 10 = as bad as you can imagine. The total score was calculated by averaging all 6 items and therefore the score ranged from 0 to 10. Higher scores indicated worse outcomes. Baseline value was average of the data from Day -6 to Day -1.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=85 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=85 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Change From Baseline to Week 12 in Asthma Nighttime Symptom Diary (ANSD)	-1.58 Score on a scale Standard Error 0.178	-1.36 Score on a scale Standard Error 0.178

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Week 12

Population: The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported.

FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. For pre-BD FEV1, spirometry was performed before IMP administration and after withholding the standard of care asthma treatment which was verified before performing the measurements. Baseline was defined as the last available valid (non-missing) value up to and including the day of first dose of IMP.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=100 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=99 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Change From Baseline to Week 12 in Pre-Bronchodilator Forced Expiratory Volume (Pre-BD FEV1)	0.49 Liter Standard Error 0.044	0.27 Liter Standard Error 0.047

SECONDARY outcome

Timeframe: From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks

Population: Safety analysis set included all randomized participants who took at least 1 dose of study intervention.

AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs: AEs that developed or worsened or became serious during TEAE period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 98 days or until participant switches to commercialized dupilumab or other biologics. SAE: 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. AESI: AE (serious or nonserious) of scientific and medical concern specific to Sponsor's product or program, for which ongoing monitoring and immediate notification by Investigator to Sponsor is required.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=100 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=101 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events Of Special Interest (TEAESIs) Any TEAE	48 Participants	46 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events Of Special Interest (TEAESIs) Any TESAE	3 Participants	3 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events Of Special Interest (TEAESIs) Any TEAESI	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks

Population: Safety analysis set included all randomized participants who took at least 1 dose of study intervention.

Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and weight. Criteria for PCSA: SBP: ≤95 millimeters of mercury (mmHg) and decrease from baseline ≥20 mmHg, ≥160 mmHg and increase from baseline ≥20 mmHg; DBP: ≤45 mmHg and decrease from baseline ≥10 mmHg, ≥ 110 mmHg and increase from baseline ≥ 10 mmHg; HR: ≤ 50 beats per minute (bpm) and decrease from baseline ≥ 20 bpm, ≥120 bpm and increase from baseline ≥ 20 bpm; Weight: ≥ 5% increase from baseline, ≥5% decrease from baseline.

Outcome measures

Measure	Dupilumab 200 mg Q2W n=100 Participants Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=101 Participants Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs SBP: ≤95 mmHg and decrease from baseline ≥20 mmHg	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs SBP: ≥160 mmHg and increase from baseline ≥20 mmHg	1 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs DBP: ≤45 mmHg and decrease from baseline ≥10 mmHg	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs DBP: ≥ 110 mmHg and increase from baseline ≥ 10mmHg	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs HR: ≤ 50 bpm and decrease from baseline ≥ 20 bpm	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs HR: ≥ 120 bpm and increase from baseline ≥ 20 bpm	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs Weight: ≥5% increase from baseline	3 Participants	6 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs Weight: ≥5% decrease from baseline	5 Participants	4 Participants

Adverse Events

Dupilumab 200 mg Q2W

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dupilumab 200 mg Q2W n=100 participants at risk Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=101 participants at risk Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Gastrointestinal disorders Pancreatitis Acute	0.00% 0/100 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	0.99% 1/101 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.
Infections and infestations Covid-19 Pneumonia	0.00% 0/100 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	0.99% 1/101 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.
Infections and infestations Urosepsis	0.00% 0/100 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	0.99% 1/101 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.
Injury, poisoning and procedural complications Fall	1.0% 1/100 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	0.00% 0/101 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.
Injury, poisoning and procedural complications Tibia Fracture	1.0% 1/100 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	0.00% 0/101 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.
Psychiatric disorders Depression Suicidal	1.0% 1/100 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	0.00% 0/101 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.
Psychiatric disorders Suicide Attempt	1.0% 1/100 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	0.00% 0/101 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.
Renal and urinary disorders Nephrolithiasis	0.00% 0/100 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	0.99% 1/101 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Asthma	1.0% 1/100 • Number of events 1 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	0.00% 0/101 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.

Other adverse events

Measure	Dupilumab 200 mg Q2W n=100 participants at risk Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.	Placebo n=101 participants at risk Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
Infections and infestations Nasopharyngitis	4.0% 4/100 • Number of events 4 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	6.9% 7/101 • Number of events 7 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Asthma	9.0% 9/100 • Number of events 11 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.	13.9% 14/101 • Number of events 17 • TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months. Analysis was performed on safety population.

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610 ext 6#

Email: Contact-US@sanofi.com

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