Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of Dupilumab in Patients With Persistent Moderate to Severe Eosinophilic Asthma (NCT NCT01312961)

Last Updated: 2017-06-08

Results Overview

An asthma exacerbation was defined as the occurrence of any of the following: ≥30% reduction from baseline in morning PEF on 2 consecutive days; or ≥6 additional reliever puffs of albuterol or levalbuterol in a 24-hour period (compared to baseline) on 2 consecutive days; or deterioration of asthma, as determined by the investigator, requiring systemic steroid treatment, or an increase in inhaled corticosteroid (ICS) of ≥4 times the last dose received prior to discontinuation from the study, or hospitalization. The occurrence of asthma exacerbations by individual criteria are reported.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

104 participants

Primary outcome timeframe

Baseline up to Week 12

Results posted on

2017-06-08

Participant Flow

The study was conducted at 50 sites in the United States. A total of 491 participants were screened between March 2011 and June 2012, of whom 104 were randomized at 28 sites. A total of 387 participants were screen failures mainly due to inclusion criteria for eosinophilic asthma not met.

Randomization was stratified according to prior inhaled corticosteroids/long-acting beta2-adrenergic agonist (ICS/LABA) combination therapy dose. Assignment to arms was done centrally using Interactive Voice Response System in 1:1 ratio to receive either Dupilumab 300 mg or Placebo.

Participant milestones

Participant milestones
Measure	Placebo (for Dupilumab) Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol were given as rescue medication.	Dupilumab 300 mg qw Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Overall Study STARTED	52	52
Overall Study Treated	52	52
Overall Study COMPLETED	35	45
Overall Study NOT COMPLETED	17	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (for Dupilumab) Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol were given as rescue medication.	Dupilumab 300 mg qw Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Overall Study Adverse Event	3	3
Overall Study Lack of Efficacy	11	1
Overall Study Poor compliance to protocol	1	0
Overall Study Other than specified above	2	3

Baseline Characteristics

Number of participants analyzed = participants with available data for this baseline measure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (for Dupilumab) n=52 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol were given as rescue medication.	Dupilumab 300 mg qw n=52 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Total n=104 Participants Total of all reporting groups
Age, Continuous	41.6 years STANDARD_DEVIATION 13.1 • n=52 Participants	37.8 years STANDARD_DEVIATION 13.2 • n=52 Participants	39.7 years STANDARD_DEVIATION 13.2 • n=104 Participants
Sex: Female, Male Female	26 Participants n=52 Participants	26 Participants n=52 Participants	52 Participants n=104 Participants
Sex: Female, Male Male	26 Participants n=52 Participants	26 Participants n=52 Participants	52 Participants n=104 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=52 Participants	12 Participants n=52 Participants	16 Participants n=104 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=52 Participants	40 Participants n=52 Participants	88 Participants n=104 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=52 Participants	0 Participants n=52 Participants	0 Participants n=104 Participants
Race Caucasian/White	38 Participants n=52 Participants	45 Participants n=52 Participants	83 Participants n=104 Participants
Race Black	9 Participants n=52 Participants	5 Participants n=52 Participants	14 Participants n=104 Participants
Race Asian/Oriental	3 Participants n=52 Participants	1 Participants n=52 Participants	4 Participants n=104 Participants
Race Other than specified above	2 Participants n=52 Participants	1 Participants n=52 Participants	3 Participants n=104 Participants
Prior ICS/LABA Combination Therapy Dose High Dose	41 Participants n=52 Participants	42 Participants n=52 Participants	83 Participants n=104 Participants
Prior ICS/LABA Combination Therapy Dose Medium Dose	11 Participants n=52 Participants	10 Participants n=52 Participants	21 Participants n=104 Participants
Morning Peak Expiratory Flow (PEF)	406.87 L/min STANDARD_DEVIATION 110.74 • n=52 Participants • Number of participants analyzed = participants with available data for this baseline measure.	393.04 L/min STANDARD_DEVIATION 101.13 • n=51 Participants • Number of participants analyzed = participants with available data for this baseline measure.	400.02 L/min STANDARD_DEVIATION 105.80 • n=103 Participants • Number of participants analyzed = participants with available data for this baseline measure.
Number of Inhalations of Albuterol or Levalbuterol in a 24-hour Period	2.04 number of inhalations STANDARD_DEVIATION 1.78 • n=52 Participants • Number of participants analyzed = participants with available data for this baseline measure.	2.16 number of inhalations STANDARD_DEVIATION 2.40 • n=50 Participants • Number of participants analyzed = participants with available data for this baseline measure.	2.10 number of inhalations STANDARD_DEVIATION 2.10 • n=102 Participants • Number of participants analyzed = participants with available data for this baseline measure.

PRIMARY outcome

Timeframe: Baseline up to Week 12

Population: Modified intent-to-treat (mITT) population that included all randomized participants who received at least one dose of study drug. Participants were analysed in the treatment group to which they were randomized.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=52 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=52 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Percentage of Participants With Asthma Exacerbation Asthma exacerbation	44.2 percentage of participants	5.8 percentage of participants
Percentage of Participants With Asthma Exacerbation ≥30% reduction from baseline in morning PEF	19.2 percentage of participants	1.9 percentage of participants
Percentage of Participants With Asthma Exacerbation ≥6additional albuterol/levalbuterol puffs	19.2 percentage of participants	1.9 percentage of participants
Percentage of Participants With Asthma Exacerbation Systemic steroid treatment	9.6 percentage of participants	1.9 percentage of participants
Percentage of Participants With Asthma Exacerbation Increase in ICS ≥4 times baseline dose of ICS	5.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With Asthma Exacerbation Hospitalization	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: mITT population.

The time-to-asthma exacerbation was defined as the time from the date of randomization to the date of the first asthma exacerbation event; for participants without asthma exacerbation, it was censored at the end of treatment visit date. The median time to first asthma exacerbation was not estimated because the number of asthma exacerbations was too low in the Dupilumab arm. Therefore, alternative Kaplan-Meier statistics, the probability of asthma exacerbation at Week 4, 8 and 12, are presented as the descriptive measure statistics.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=52 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=52 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Time to First Asthma Exacerbation: Kaplan-Meier Estimates at Week 4, Week 8 and Week 12 Probability at Week 4	0.058 Probability of asthma exacerbation Interval 0.0 to 0.122	0.038 Probability of asthma exacerbation Interval 0.0 to 0.091
Time to First Asthma Exacerbation: Kaplan-Meier Estimates at Week 4, Week 8 and Week 12 Probability at Week 8	0.245 Probability of asthma exacerbation Interval 0.124 to 0.366	0.058 Probability of asthma exacerbation Interval 0.0 to 0.121
Time to First Asthma Exacerbation: Kaplan-Meier Estimates at Week 4, Week 8 and Week 12 Probability at Week 12	0.460 Probability of asthma exacerbation Interval 0.318 to 0.602	0.058 Probability of asthma exacerbation Interval 0.0 to 0.121

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: mITT population.

Composite asthma event was defined as a 30% or greater reduction from baseline in morning PEF on 2 consecutive days together with 6 or more additional reliever puffs of albuterol or levalbuterol in a 24-hour period (compared to baseline) on 2 consecutive days.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=52 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=52 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Percentage of Participants With Composite Asthma Events	1.9 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT population. Number of participants analyzed = participants with at least one post-baseline assessment.

FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=36 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=45 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Change From Baseline in Forced Expiratory Flow in One Second (FEV1) to Week 12	-0.12 Liters Standard Deviation 0.35	0.06 Liters Standard Deviation 0.32

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT population. Number analyzed = participants with at least one post-baseline assessment for each category.

The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at home (morning and evening) while sitting or standing prior to using any medication (if needed) for asthma.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=52 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=52 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Change From Baseline in Peak Expiratory Flow (PEF) to Week 12 Change in morning PEF	-11.2 liters/minute Standard Deviation 66.1	10.6 liters/minute Standard Deviation 48.5
Change From Baseline in Peak Expiratory Flow (PEF) to Week 12 Change in evening PEF	-15.6 liters/minute Standard Deviation 70.7	-3.4 liters/minute Standard Deviation 49.3

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT population. Number of participants analyzed = participants with at least one post-baseline assessment.

ACQ-5 questionnaire is a validated questionnaire comprising of 5 questions for asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath, and wheeze. Participants were asked to rate their asthma symptoms during the previous week on a 7-point scale as 0=no impairment, 6=maximum impairment. ACQ-5 score is the mean of the 5 questions and range between 0 (disease totally controlled) and 6 (disease severely uncontrolled), a higher score indicated lower asthma control.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=36 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=44 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Change From Baseline in Asthma Control Questionnaire (5-question Version [ACQ-5]) to Week 12	-0.50 units on a scale Standard Deviation 1.12	-1.07 units on a scale Standard Deviation 0.94

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT population. Number of participants analyzed = participants with at least one post-baseline assessment.

The SNOT-22 is a validated measure of health related quality of life in sinonasal disease. It is a 22 item questionnaire with each item assigned a score ranging from 0-5. The total score may range from 0 (no disease) -110 (worst disease), lower scores represent better health related quality of life.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=51 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=50 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Change From Baseline in 22-item Sinonasal Outcome Test (SNOT-22) Score to Week 12	1.27 units on a scale Standard Deviation 15.85	-9.17 units on a scale Standard Deviation 15.40

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT population. Number of participants analyzed = participants with at least one post-baseline assessment.

AM (ante meridiem) symptom scoring system rates were participant's overall asthma symptoms experienced during the night. It ranges from 0 to 4 as: 0 = No asthma symptoms, slept through the night, 1= Slept well, but some complaints in the morning. No nighttime awakenings,2= Woke up once because of asthma (including early awakening),3= Woke up several times because of asthma (including early awakening), 4= Bad night, awake most of the night because of asthma.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=36 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=45 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Change From Baseline in Morning Asthma Symptom Scores to Week 12	0.3 units on a scale Standard Deviation 0.7	-0.4 units on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT population. Number of participants analyzed = participants with at least one post-baseline assessment.

PM (post meridiem) symptom scoring system rates were participant's overall asthma symptoms experienced during the day. It ranges from 0 to 4 as: 0=very well, no asthma symptoms, 1=one episode of wheezing, cough, or breathlessness, 2=more than one episode of wheezing, cough, or breathlessness without interference of normal activities, 3=wheezing, cough, or breathlessness most of the day, which interfered to some extent with normal activities, 4=asthma very bad, unable to carry out daily activities as usual.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=36 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=45 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Change From Baseline in Evening Asthma Symptom Scores to Week 12	0.1 units on a scale Standard Deviation 0.9	-0.5 units on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT population. Number of participants analyzed = participants with at least one post-baseline assessment.

Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=36 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=45 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Change From Baseline in Number of Nocturnal Awakenings Per Day to Week 12	0.1 number of awakenings/day Standard Deviation 0.7	-0.3 number of awakenings/day Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT population. Number of participants analyzed = participants with at least one post-baseline assessment.

Number of Albuterol or Levalbuterol inhalations were recorded daily by the participants in their electronic diary as Albuterol or Levalbuterol was to be used only as needed for symptoms, not on a regular basis or prophylactically.

Outcome measures

Outcome measures
Measure	Placebo (for Dupilumab) n=36 Participants Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.	Dupilumab 300 mg qw n=44 Participants Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
Change From Baseline in Number of Inhalations Per Day of Albuterol or Levalbuterol to Week 12	0.4 number of inhalations/day Standard Deviation 2.4	-1.3 number of inhalations/day Standard Deviation 1.7

Adverse Events

Placebo (for Dupilumab)

Serious events: 3 serious events

Other events: 24 other events

Deaths: 0 deaths

Dupilumab 300 mg qw

Serious events: 1 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo (for Dupilumab) n=52 participants at risk Participants exposed to Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (mean exposure of 11 weeks).	Dupilumab 300 mg qw n=52 participants at risk Participants exposed to Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (mean exposure of 11 weeks).
Infections and infestations Pneumonia	1.9% 1/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Psychiatric disorders Bipolar disorder	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	1.9% 1/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Respiratory, thoracic and mediastinal disorders Asthma	1.9% 1/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.9% 1/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Injury, poisoning and procedural complications Ankle fracture	1.9% 1/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Injury, poisoning and procedural complications Gun shot wound	1.9% 1/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo (for Dupilumab) n=52 participants at risk Participants exposed to Placebo (for Dupilumab) SC injection qw for 12 weeks added to background therapy of ICS/LABA (mean exposure of 11 weeks).	Dupilumab 300 mg qw n=52 participants at risk Participants exposed to Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (mean exposure of 11 weeks).
Infections and infestations Gastroenteritis viral	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Infections and infestations Nasopharyngitis	3.8% 2/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	13.5% 7/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Infections and infestations Sinusitis	9.6% 5/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	1.9% 1/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Infections and infestations Upper respiratory tract infection	17.3% 9/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	13.5% 7/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Infections and infestations Viral upper respiratory tract infection	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Nervous system disorders Headache	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	11.5% 6/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.9% 1/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Respiratory, thoracic and mediastinal disorders Rhinitis seasonal	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Gastrointestinal disorders Nausea	1.9% 1/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	7.7% 4/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Skin and subcutaneous tissue disorders Rash	1.9% 1/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
General disorders Injection site erythema	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
General disorders Injection site pain	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	9.6% 5/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
General disorders Injection site rash	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
General disorders Injection site reaction	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	9.6% 5/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).	5.8% 3/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment emergent AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first dose of investigatory medicinal product (IMP) up to the end of the follow-up period \[i.e. up to 7 weeks after the last dose of IMP\]).