VENTURE: Evaluation of Dupilumab in Patients With Severe Steroid Dependent Asthma

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02528214
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 210
• Locations: 80
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary Objective:

To evaluate the efficacy of dupilumab, compared with placebo, for reducing the use of maintenance oral corticosteroids (OCS) in participants with severe steroid-dependent asthma.

Secondary Objectives:

• To evaluate the safety and tolerability of dupilumab.

• To evaluate the effect of dupilumab in improving participants-reported outcomes.

• To evaluate dupilumab systemic exposure and the incidence of treatment-emergent antidrug antibodies.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Dupilumab; Drug: Placebo; Drug: Oral corticosteroid therapy (prednisone/prednisolone); Drug: Inhaled corticosteroid (ICS) therapy; Drug: Albuterol/Salbutamol; Drug: Levalbuterol/Levosalbutamol	Phase 3

Detailed Description

The total study duration per participant was up to 46 weeks, consisting of a screening period of 3 to up to 8 weeks (up to 10 weeks for participants who experienced a clinically significant asthma exacerbation during the screening period), a randomized treatment period of up to 24 weeks, and a post-treatment period of 12 weeks.

Participants who completed treatment were considered for eligibility into the long term extension study LTS12551 (NCT02134028).

Study Design

• Study Type: Interventional
• Actual Enrollment: 210 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Severe Steroid Dependent Asthma
• Study Start Date: Oct 15, 2015
• Actual Primary Completion Date: Sep 20, 2017
• Actual Study Completion Date: Nov 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo q2w 2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable inhaled corticosteroid (ICS). OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.	Drug: Placebo; Solution for injection, Subcutaneous injection in the abdomen, upper thigh or upper arm.; Drug: Oral corticosteroid therapy (prednisone/prednisolone); Oral administration.; Drug: Inhaled corticosteroid (ICS) therapy; Oral inhalation, stable dose (high dose) of ICS in combination with up to 2 other controller medicines (second or third controller therapy).; Drug: Albuterol/Salbutamol; Oral inhalation as needed.; Drug: Levalbuterol/Levosalbutamol; Oral inhalation as needed.
Experimental: Dupilumab 300 mg q2w 2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.	Drug: Dupilumab; Solution for injection, Subcutaneous injection in the abdomen, upper thigh or upper arm.; Other Names: REGN668 SAR231893 ; Drug: Oral corticosteroid therapy (prednisone/prednisolone); Oral administration.; Drug: Inhaled corticosteroid (ICS) therapy; Oral inhalation, stable dose (high dose) of ICS in combination with up to 2 other controller medicines (second or third controller therapy).; Drug: Albuterol/Salbutamol; Oral inhalation as needed.; Drug: Levalbuterol/Levosalbutamol; Oral inhalation as needed.

Outcome Measures

Primary Outcome Measures

1. Percentage Reduction From Baseline in Oral Corticosteroids (OCS) Dose at Week 24 While Maintaining Asthma Control [Baseline, Week 24]

   Percentage reduction of OCS dose was calculated as (optimized OCS dose [mg/day] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100. Result is presented as Least Squares Mean (Standard Error) percentage reduction from baseline derived from ANCOVA model with missing data multiply imputed.

2. Supplementary Presentation of Primary Outcome Measure Data: Median Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control [Baseline, Week 24]

   The Primary Outcome Measure (Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control) is summarized above, as LS Mean (SE). Table below provides a supplementary presentation of the Primary Outcome Measure data; result is presented as median (inter-quartile range). Percentage reduction of OCS dose was calculated as (optimized OCS dose [mg/day] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100.

Secondary Outcome Measures

1. Percentage of Participants Achieving >= 50% Reduction in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control [Week 24]

   Participants were classified according to the binary status of whether or not the 50% OCS dose reduction criterion was achieved at week 24.

2. Percentage of Participants Achieving a Reduction in Oral Corticosteroids Dose to <5 mg/Day at Week 24 While Maintaining Asthma Control [Week 24]

   Participants were classified according to the binary status of whether or not the reduction of OCS dose to <5 mg/day was achieved at Week 24.

3. Percentage of Participants Achieving Maximum Possible Reduction in Oral Corticosteroids Dose Per Protocol at Week 24 While Maintaining Asthma Control [Week 24]

   For all participants except those with baseline OCS dose at 35 mg/day, the maximum possible reduction corresponds to reduction to 0 mg/day (no longer requiring OCS). For participants starting with 35 mg/day at baseline, the maximum possible reduction is 32.5 mg/day (i.e. minimum dose per protocol is 2.5 mg).

4. Percentage of Participants Who No Longer Required Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control [Week 24]

   Participants were classified according to the binary status of whether or not the participant still required OCS at Week 24 while maintaining asthma control.

5. Absolute Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control [Baseline and Week 24]

   Absolute reduction was calculated by subtracting Week 24 value from baseline value.

Other Outcome Measures

1. Annualized Rate of Severe Exacerbation Events During The 24-Week Treatment Period [Baseline to Week 24]

   A severe asthma exacerbation event was defined as a deterioration of asthma during the 24-week treatment period requiring: use of systemic corticosteroids for >=3 days (at least double the dose currently used); and/or hospitalization related to asthma symptoms or emergency room visit because of asthma requiring intervention with a systemic corticosteroid treatment. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.

2. Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Weeks 12 and 24 [Baseline, Week 12 and Week 24]

   FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.

3. Change From Baseline in Asthma Control Questionnaire 5-Question Version (ACQ-5) Score at Weeks 2, 4, 8, 12, 16, 20, and 24 [Baseline and at Weeks 2, 4, 8, 12, 16, 20, and 24]

   The ACQ-5 has 5 questions, reflecting top-scoring 5 asthma symptoms: woken at night by symptoms, wake in mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during previous week and to respond to each of 5 symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total score was mean of scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control.

4. Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12 and Week 24 [Baseline, Week 12 and Week 24]

   AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that were most important to participants with asthma. AQLQ comprised of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item was scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire were averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life.

5. Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Scores at Week 12 and Week 24 [Baseline, Week 12 and Week 24]

   EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable).

6. Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 12 and Week 24 [Baseline, Week 12 and Week 24]

   The HADS is a general scale to detect states of anxiety and depression already used and validated in asthma, which includes HADS-A and HADS-D subscales. The instrument is comprised of 14 items: 7 related to anxiety (HADS-A) and 7 to depression (HADS-D). Each item on the questionnaire is scored from 0-3. And, the total score is the sum of the scores of the 14 items ranging from 0 (no symptoms) to 42 (severe symptoms), with higher scores indicating higher anxiety/depression complains.

7. Change From Baseline in Sino Nasal Outcome Test-22 (SNOT-22) Global Score at Week 12 and Week 24 [Baseline, Week 12 and Week 24]

   The SNOT-22 is a validated measure of health related quality of life in sino nasal 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria :

Adult and adolescent (12 years of age or older) participants with a physician diagnosis of asthma for >=12 months, based on the Global Initiative for Asthma (GINA) 2014 guidelines and the following criteria:

• Participants with severe asthma and a well-documented, regular prescribed treatment of maintenance corticosteroids in the 6 months prior to Visit 1 and using a stable OCS dose (ie, no change of OCS dose) for 4 weeks prior to Visit 1. Participants must be taking 5 to 35 mg/day of prednisone/prednisolone, or the equivalent, at Visit 1 and at the randomization visit. In addition, the participants must agree to switch to study-required prednisone/prednisolone as their OCS and use it per protocol for the duration of the study.

• Existing treatment with high-dose inhaled corticosteroid (ICS; >500 mcg total daily dose of fluticasone propionate or equivalent) in combination with a second controller (ie, long-acting beta agonist [LABA], leukotriene receptor antagonist [LTRA]) for at least 3 months with a stable dose of ICS for >=1 month prior to Visit 1. In addition, participants requiring a third controller for their asthma are considered eligible for this study, and it should also be used for at least 3 months with a stable dose >= 1 month prior to Visit 1.

• A forced expiratory volume in 1 second (FEV1) <80% of predicted normal for adults and <=90% of predicted normal for adolescents at Visit 1.

• Evidence of asthma as documented by either: reversibility of at least 12% and 200 mL in FEV1 after the administration of 200 to 400 mcg (2 to 4 inhalations of albuterol/salbutamol or levalbuterol/levosalbutamol, or of a nebulized solution of albuterol/salbutamol or levalbuterol/levosalbutamol, if considered as a standard office practice) before randomization or documented in the 12 months prior to Visit 1 OR airway hyperresponsiveness (methacholine: provocative concentration that causes a positive reaction [PC20] of <8 mg/mL) documented in the 12 months prior to Visit 1.

Exclusion criteria:

• Participants <12 years of age or the minimum legal age for adolescents in the country of the investigative site, whichever is higher (for those countries where local regulations permit enrollment of adults only, participant recruitment will be restricted to those who were >=18 years of age).

• Participants who weighed <30.0 kg.

• Chronic obstructive pulmonary disease (COPD) or other lung diseases (eg, idiopathic pulmonary fibrosis, Churg-Strauss Syndrome, allergic bronchopulmonary aspergillosis, cystic fibrosis) which may impair lung function.

• Clinical evidence or imaging (eg, chest X-ray, computed tomography, magnetic resonance imaging) within 12 months of Visit 1 with clinically significant findings of lung disease(s) other than asthma, as per local standard of care.

• A participant who experiences a deterioration of asthma that results in emergency treatment or hospitalization within 4 weeks of Screening Visit 1.

• A participant who requires 12 puffs or more of rescue medication on any 1 day in the week prior to Visit 1.

• A participant who has experienced an upper or lower respiratory tract infection within the 4 weeks prior to screening.

• Current smoker or cessation of smoking within 6 months prior to Visit 1.

• Previous smoker with a smoking history >10 pack-years.

• Comorbid disease that might interfere with the evaluation of the investigational medicinal product.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840022	Los Angeles	California	United States	90048
2	Investigational Site Number 840014	Rolling Hills Estates	California	United States	90274
3	Investigational Site Number 840002	Saint Louis	Missouri	United States	63110
4	Investigational Site Number 840010	Pittsburgh	Pennsylvania	United States	15213
5	Investigational Site Number 840062	Amarillo	Texas	United States	79106
6	Investigational Site Number 840070	McKinney	Texas	United States	75069
7	Investigational Site Number 840128	McKinney	Texas	United States	75071
8	Investigational Site Number 840118	Plano	Texas	United States	75093
9	Investigational Site Number 032003	Buenos Aires		Argentina	C1121ABE
10	Investigational Site Number 032001	Caba		Argentina	C1425BEN
11	Investigational Site Number 032091	Caba		Argentina	C1426ABP
12	Investigational Site Number 056002	Brussels		Belgium	1020
13	Investigational Site Number 056003	Gent		Belgium	9000
14	Investigational Site Number 056001	Leuven		Belgium	3000
15	Investigational Site Number 076011	Sao Paulo		Brazil	04020-041
16	Investigational Site Number 076002	Sorocaba		Brazil	18040-425
17	Investigational Site Number 076013	São Bernardo Do Campo		Brazil	09780-000
18	Investigational Site Number 124009	Calgary		Canada	T2N 4Z6
19	Investigational Site Number 124016	Hamilton		Canada	L8N 4A6
20	Investigational Site Number 124003	Mississauga		Canada	L5A 3V4
21	Investigational Site Number 124013	Ottawa		Canada	K1G 6C6
22	Investigational Site Number 124002	Toronto		Canada	M5T 3A9
23	Investigational Site Number 124017	Vancouver		Canada	V6Z 1Y6
24	Investigational Site Number 152007	Quillota		Chile	2260877
25	Investigational Site Number 152005	Santiago		Chile	7500692
26	Investigational Site Number 152008	Talca		Chile	3460001
27	Investigational Site Number 170001	Bogota		Colombia	110121
28	Investigational Site Number 170006	Bogota		Colombia
29	Investigational Site Number 348301	Balassagyarmat		Hungary	2660
30	Investigational Site Number 348303	Edelény		Hungary	3780
31	Investigational Site Number 376003	Haifa		Israel	34362
32	Investigational Site Number 376001	Kfar Saba		Israel	44281
33	Investigational Site Number 376005	Petah-Tikva		Israel	49100
34	Investigational Site Number 376002	Rehovot		Israel	76100
35	Investigational Site Number 376004	Tel Hashomer		Israel	52621
36	Investigational Site Number 380005	Catania		Italy	95123
37	Investigational Site Number 380002	Genova		Italy	16132
38	Investigational Site Number 380008	Napoli		Italy	80131
39	Investigational Site Number 380009	Palermo		Italy	90146
40	Investigational Site Number 380001	Pisa		Italy	56124
41	Investigational Site Number 380003	Reggio Emilia		Italy	42123
42	Investigational Site Number 484016	Acapulco		Mexico	39670
43	Investigational Site Number 484013	Chihuahua		Mexico	31020
44	Investigational Site Number 484001	Guadalajara		Mexico	44100
45	Investigational Site Number 484002	Mexico, Df		Mexico	06726
46	Investigational Site Number 484003	Monterrey		Mexico	64460
47	Investigational Site Number 528001	Arnhem		Netherlands	6815 AD
48	Investigational Site Number 528002	Dordrecht		Netherlands	3318 AT
49	Investigational Site Number 616006	Bialystok		Poland	15-010
50	Investigational Site Number 616097	Krakow		Poland	31-159
51	Investigational Site Number 616001	Lodz		Poland	90-141
52	Investigational Site Number 616010	Warszawa		Poland	04-141
53	Investigational Site Number 616011	Znin		Poland	88-400
54	Investigational Site Number 642104	Bucharest		Romania	011461
55	Investigational Site Number 642103	Bucharest		Romania	050159
56	Investigational Site Number 642102	Cluj-Napoca		Romania	400162
57	Investigational Site Number 642107	Cluj-Napoca		Romania	400371
58	Investigational Site Number 642108	Cluj-Napoca		Romania	400371
59	Investigational Site Number 642105	Timisoara		Romania	300310
60	Investigational Site Number 642106	Timisoara		Romania	300310
61	Investigational Site Number 643006	Moscow		Russian Federation	105077
62	Investigational Site Number 643007	Moscow		Russian Federation	117574
63	Investigational Site Number 643011	Saint-Petersburg		Russian Federation	194356
64	Investigational Site Number 643099	St-Petersburg		Russian Federation	193231
65	Investigational Site Number 643009	St-Petersburg		Russian Federation	197022
66	Investigational Site Number 724014	Barcelona		Spain	08023
67	Investigational Site Number 724002	Barcelona		Spain	08035
68	Investigational Site Number 724013	Madrid		Spain	28942
69	Investigational Site Number 724006	Pozuelo De Alarcón		Spain	28223
70	Investigational Site Number 724007	Sant Boi De Llobregat		Spain	08830
71	Investigational Site Number 724096	Santiago De Compostela		Spain	15706
72	Investigational Site Number 804007	Chernivtsi		Ukraine	58001
73	Investigational Site Number 804004	Ivano-Frankivsk		Ukraine	76018
74	Investigational Site Number 804009	Ivano-Frankivsk		Ukraine	76018
75	Investigational Site Number 804001	Kharkiv		Ukraine	61124
76	Investigational Site Number 804003	Kyiv		Ukraine	03680
77	Investigational Site Number 804011	Kyiv		Ukraine	03680
78	Investigational Site Number 804006	Odessa		Ukraine	65025
79	Investigational Site Number 804002	Poltava		Ukraine	36038
80	Investigational Site Number 804019	Vinnytsya		Ukraine	21001

Sponsors and Collaborators

• Sanofi
• Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Jan 25, 2017
• Statistical Analysis Plan - May 18, 2017

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02528214
• Other Study ID Numbers: EFC13691; 2015-001573-40; U1111-1170-7152
• First Posted: Aug 19, 2015
• Last Update Posted: Oct 1, 2019
• Last Verified: Nov 1, 2017

• Additional relevant MeSH terms: Asthma; Prednisone; Prednisolone; Albuterol

Study Results

Participant Flow

Recruitment Details	The study was conducted at 68 centers in 17 countries. A total of 390 participants were screened between October 2015 & April 2017, of which,210 were randomized & treated. 180 participants were screen failures mainly due to exclusion criteria met & inclusion criteria not met. Assignment was done by Interactive Voice/Web Response System(IVRS/IWRS).
Pre-assignment Detail	Screening period included an OCS optimization phase (up to 10 weeks) where participants using OCS other than prednisone/prednisolone switched to these OCS. At the end of period, participants were randomized in 1:1 ratio (dupilumab:placebo).Randomization was stratified by optimized OCS dose (=<10 & >10 mg/day) at randomization visit & by country.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection every 2 weeks (q2w) for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Period Title: Overall Study
STARTED	107	103
Treated	107	103
COMPLETED	107	100
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w	Total
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	Total of all reporting groups
Overall Participants	107	103	210
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.7 (12.8)	51.9 (12.5)	51.3 (12.6)
Age, Customized (Count of Participants)
<18 years	2 1.9%	1 1%	3 1.4%
Between 18 and 64 years	88 82.2%	91 88.3%	179 85.2%
>=65 years	17 15.9%	11 10.7%	28 13.3%
Sex: Female, Male (Count of Participants)
Female	65 60.7%	62 60.2%	127 60.5%
Male	42 39.3%	41 39.8%	83 39.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	22 20.6%	23 22.3%	45 21.4%
Not Hispanic or Latino	85 79.4%	80 77.7%	165 78.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Caucasian/White	100 93.5%	97 94.2%	197 93.8%
Black/of African descent	1 0.9%	4 3.9%	5 2.4%
Asian/Oriental	2 1.9%	0 0%	2 1%
American Indian or Alaska Native	2 1.9%	0 0%	2 1%
Native Hawaiian or Other Pacific Islander	0 0%	1 1%	1 0.5%
Other	2 1.9%	1 1%	3 1.4%
Baseline Blood Eosinophil Count (Count of Participants)
<0.15 Giga/L	38 35.5%	22 21.4%	60 28.6%
>=0.15 - <0.3 Giga/L	28 26.2%	33 32%	61 29%
>=0.3 Giga/L	41 38.3%	48 46.6%	89 42.4%
Baseline Optimized Daily OCS Dose (mg/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/day]	11.75 (6.31)	10.75 (5.9)	11.26 (6.12)
Daily OCS Dose at Visit 1 (i.e. preoptimization) (mg/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/day]	11.83 (6.02)	11.79 (6.4)	11.81 (6.20)

Outcome Measures

1. Primary Outcome

Title	Percentage Reduction From Baseline in Oral Corticosteroids (OCS) Dose at Week 24 While Maintaining Asthma Control
Description	Percentage reduction of OCS dose was calculated as (optimized OCS dose [mg/day] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100. Result is presented as Least Squares Mean (Standard Error) percentage reduction from baseline derived from ANCOVA model with missing data multiply imputed.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on intent-to-treat (ITT) population which included randomized population analysed according to the treatment group allocated by randomization regardless of whether the treatment kit was used or not.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Least Squares Mean (Standard Error) [Percentage reduction from baseline]	41.85 (4.57)	70.09 (4.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Dupilumab 300 mg q2w
	Comments	The outcome measure was analyzed using analysis of covariance (ANCOVA) model which included percentage reduction of OCS dose at Week 24 as the response variable, and treatment group, baseline eosinophil level, optimized OCS dose at baseline, region as covariates. Missing data was imputed using a pattern mixture model by multiple imputation approach.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measure are reported and continued when previous outcome measure was statistically significant at two-sided 0.05. Only the primary and the first 4 secondary outcome measures were included in the procedure.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at two-sided 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square (LS) Mean Difference
	Estimated Value	28.24
	Confidence Interval	(2-Sided) 95%; 15.81 to 40.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS mean difference represents reduction difference i.e. dupilumab - placebo.

2. Primary Outcome

Title	Supplementary Presentation of Primary Outcome Measure Data: Median Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
Description	The Primary Outcome Measure (Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control) is summarized above, as LS Mean (SE). Table below provides a supplementary presentation of the Primary Outcome Measure data; result is presented as median (inter-quartile range). Percentage reduction of OCS dose was calculated as (optimized OCS dose [mg/day] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Analysis population included ITT patients with available data.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	106	101
Median (Inter-Quartile Range) [percentage reduction from baseline]	50.0	100.0

3. Secondary Outcome

Title	Percentage of Participants Achieving >= 50% Reduction in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
Description	Participants were classified according to the binary status of whether or not the 50% OCS dose reduction criterion was achieved at week 24.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Number [percentage of participants]	53.3 49.8%	79.6 77.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Dupilumab 300 mg q2w
	Comments	The outcome measure was analyzed using a logistic regression model. The model included the binary status of whether or not a participant achieved the 50% OCS dose reduction criterion as the response variable, and treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed by using a pattern mixture model by multiple imputation approach.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant).
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.05.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.98
	Confidence Interval	(2-Sided) 95%; 2.06 to 7.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w v Placebo q2w

4. Secondary Outcome

Title	Percentage of Participants Achieving a Reduction in Oral Corticosteroids Dose to <5 mg/Day at Week 24 While Maintaining Asthma Control
Description	Participants were classified according to the binary status of whether or not the reduction of OCS dose to <5 mg/day was achieved at Week 24.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Number [percentage of participants]	37.4 35%	71.8 69.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Dupilumab 300 mg q2w
	Comments	The outcome measure was analyzed using a logistic regression model. The model included the binary status of whether or not a participant achieved a reduction of OCS dose to <5 mg/day at Week 24 as the response variable, treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed by using a pattern mixture model by multiple imputation approach.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant).
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Threshold for significance at 0.05.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.48
	Confidence Interval	(2-Sided) 95%; 2.39 to 8.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w v Placebo q2w

5. Secondary Outcome

Title	Percentage of Participants Achieving Maximum Possible Reduction in Oral Corticosteroids Dose Per Protocol at Week 24 While Maintaining Asthma Control
Description	For all participants except those with baseline OCS dose at 35 mg/day, the maximum possible reduction corresponds to reduction to 0 mg/day (no longer requiring OCS). For participants starting with 35 mg/day at baseline, the maximum possible reduction is 32.5 mg/day (i.e. minimum dose per protocol is 2.5 mg).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Number [percentage of participants]	29.9 27.9%	52.4 50.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Dupilumab 300 mg q2w
	Comments	The outcome was analyzed using a logistic regression model. The model included binary status of whether or not a participant achieved their maximum possible reduction of OCS dose per protocol at Week 24 as the response variable, treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed by using a pattern mixture model by multiple imputation approach.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant).
Statistical Test of Hypothesis	p-Value	0.0024
	Comments	Threshold for significance at 0.05.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.57
	Confidence Interval	(2-Sided) 95%; 1.4 to 4.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w v Placebo q2w

6. Secondary Outcome

Title	Percentage of Participants Who No Longer Required Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
Description	Participants were classified according to the binary status of whether or not the participant still required OCS at Week 24 while maintaining asthma control.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population with baseline OCS dose less than or equal to 30 mg/day.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	106	103
Number [percentage of participants]	29.2 27.3%	52.4 50.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo q2w, Dupilumab 300 mg q2w
	Comments	The outcome measure was analyzed using a logistic regression model. The model included the binary status of whether or not a participant no longer required OCS at Week 24 as the response variable, and treatment groups, optimized OCS dose at baseline, regions, and baseline eosinophil level subgroups as covariates. Missing data was imputed using a pattern mixture model by multiple imputation approach.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if previous endpoints were statistically significant).
Statistical Test of Hypothesis	p-Value	0.0015
	Comments	Threshold for significance at 0.05.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.74
	Confidence Interval	(2-Sided) 95%; 1.47 to 5.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dupilumab 300 mg q2w v Placebo q2w

7. Secondary Outcome

Title	Absolute Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control
Description	Absolute reduction was calculated by subtracting Week 24 value from baseline value.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population but not included in the hierarchical testing procedure. Here, "number analyzed"= participants with available data for specified categories.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Baseline	11.75 (6.31)	10.75 (5.90)
Week 24	6.32 (6.75)	3.13 (5.44)
Absolute reduction at Week 24	5.45 (6.80)	7.66 (6.10)

8. Other Pre-specified Outcome

Title	Annualized Rate of Severe Exacerbation Events During The 24-Week Treatment Period
Description	A severe asthma exacerbation event was defined as a deterioration of asthma during the 24-week treatment period requiring: use of systemic corticosteroids for >=3 days (at least double the dose currently used); and/or hospitalization related to asthma symptoms or emergency room visit because of asthma requiring intervention with a systemic corticosteroid treatment. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed ITT population.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Number (95% Confidence Interval) [Exacerbation per participant-year]	1.597	0.649

9. Other Pre-specified Outcome

Title	Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Weeks 12 and 24
Description	FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, "number analyzed"= participants with available data for specified categories.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Baseline	1.63 (0.61)	1.53 (0.53)
Week 12	1.68 (0.61)	1.82 (0.63)
Change at Week 12	0.06 (0.50)	0.29 (0.43)
Week 24	1.63 (0.65)	1.84 (0.60)
Change at Week 24	0.00 (0.51)	0.29 (0.46)

10. Other Pre-specified Outcome

Title	Change From Baseline in Asthma Control Questionnaire 5-Question Version (ACQ-5) Score at Weeks 2, 4, 8, 12, 16, 20, and 24
Description	The ACQ-5 has 5 questions, reflecting top-scoring 5 asthma symptoms: woken at night by symptoms, wake in mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during previous week and to respond to each of 5 symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total score was mean of scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control.
Time Frame	Baseline and at Weeks 2, 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, number analyzed = participants with available data for specified categories.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Change at Week 2	-0.18 (0.67)	-0.49 (0.86)
Change at Week 4	-0.36 (0.81)	-0.61 (1.01)
Change at Week 8	-0.39 (1.13)	-0.68 (1.06)
Change at Week 12	-0.54 (1.17)	-0.92 (1.09)
Change at Week 16	-0.57 (1.05)	-0.87 (1.18)
Change at Week 20	-0.53 (1.09)	-0.83 (1.19)
Change at Week 24	-0.57 (1.19)	-0.94 (1.22)

11. Other Pre-specified Outcome

Title	Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12 and Week 24
Description	AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that were most important to participants with asthma. AQLQ comprised of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item was scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire were averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, number analyzed = participants with available data for specified categories.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Change at Week 12	0.56 (1.08)	0.78 (1.09)
Change at Week 24	0.56 (0.97)	0.94 (1.17)

12. Other Pre-specified Outcome

Title	Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Scores at Week 12 and Week 24
Description	EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable).
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, number analyzed = participants with available data for specified categories

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Single Index: Change at Week 12	0.04 (0.20)	0.03 (0.17)
Single Index: Change at Week 24	0.05 (0.18)	0.05 (0.18)
VAS Score: Change at Week 12	5.99 (16.85)	9.34 (18.20)
VAS Score: Change at Week 24	4.16 (16.74)	11.06 (17.60)

13. Other Pre-specified Outcome

Title	Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 12 and Week 24
Description	The HADS is a general scale to detect states of anxiety and depression already used and validated in asthma, which includes HADS-A and HADS-D subscales. The instrument is comprised of 14 items: 7 related to anxiety (HADS-A) and 7 to depression (HADS-D). Each item on the questionnaire is scored from 0-3. And, the total score is the sum of the scores of the 14 items ranging from 0 (no symptoms) to 42 (severe symptoms), with higher scores indicating higher anxiety/depression complains.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, number analyzed = participants with available data for specified categories.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	107	103
Change at Week 12	-0.75 (5.50)	-2.13 (5.32)
Change at Week 24	-0.99 (5.36)	-2.53 (5.98)

14. Other Pre-specified Outcome

Title	Change From Baseline in Sino Nasal Outcome Test-22 (SNOT-22) Global Score at Week 12 and Week 24
Description	The SNOT-22 is a validated measure of health related quality of life in sino nasal 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.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population with bilateral nasal polyposis/chronic rhinosinusitis. Here, number analyzed = participants with available data for specified categories.

Arm/Group Title	Placebo q2w	Dupilumab 300 mg q2w
Arm/Group Description	2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1, followed by a single injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.	2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection q2w for 24 weeks in combination with OCS - (prednisone or prednisolone) and stable ICS. OCS dose was reduced according to a predetermined titration schedule every 4 weeks until Week 20.
Measure Participants	41	31
Change at Week 12	-3.79 (21.34)	-12.45 (17.10)
Change at Week 24	-2.46 (19.11)	-14.56 (15.89)

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 36) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported AEs were treatment emergent AEs developed/worsened occurred during 'treatment-emergent period' (from first dose of study drug injection until 98 days after last dose of drug) or entry in the LTS12551 study (NCT02134028). Analysis was performed on safety population which included all participants who actually received at least 1 dose or part of a dose of the IMP and analyzed according to the treatment that participants actually received.
Arm/Group Title	Placebo q2w		Dupilumab 300mg q2w
Arm/Group Description	Participants who received Placebo (for Dupilumab) in combination with OCS and stable ICS (mean exposure of 24 weeks).		Participants who received Dupilumab 300 mg q2w in combination with OCS and stable ICS (mean exposure of 24 weeks).
All Cause Mortality
	Placebo q2w		Dupilumab 300mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		0/103 (0%)
Serious Adverse Events
	Placebo q2w		Dupilumab 300mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/107 (5.6%)		9/103 (8.7%)
Blood and lymphatic system disorders
Eosinophilia	0/107 (0%)		2/103 (1.9%)
Infections and infestations
Pneumonia	0/107 (0%)		1/103 (1%)
Respiratory tract infection	0/107 (0%)		1/103 (1%)
Injury, poisoning and procedural complications
Acetabulum fracture	0/107 (0%)		1/103 (1%)
Foreign body aspiration	0/107 (0%)		1/103 (1%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus	1/107 (0.9%)		0/103 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal stromal tumour	1/107 (0.9%)		0/103 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	3/107 (2.8%)		3/103 (2.9%)
Asthmatic crisis	1/107 (0.9%)		0/103 (0%)
Chylothorax	0/107 (0%)		1/103 (1%)
Pneumonia aspiration	0/107 (0%)		1/103 (1%)
Pneumothorax	0/107 (0%)		1/103 (1%)
Pulmonary mass	0/107 (0%)		1/103 (1%)
Other (Not Including Serious) Adverse Events
	Placebo q2w		Dupilumab 300mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/107 (28%)		29/103 (28.2%)
Infections and infestations
Bronchitis	6/107 (5.6%)		7/103 (6.8%)
Influenza	6/107 (5.6%)		3/103 (2.9%)
Sinusitis	4/107 (3.7%)		7/103 (6.8%)
Viral upper respiratory tract infection	19/107 (17.8%)		9/103 (8.7%)
Investigations
Eosinophil count increased	0/107 (0%)		7/103 (6.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.