Efficacy and Safety Study of Dupilumab in Patients With Persistent Asthma

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT03782532

Collaborator

Regeneron Pharmaceuticals (Industry)

486

Enrollment

Locations

Arms

39.8

Actual Duration (Months)

7.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To evaluate the efficacy of dupilumab in patients with persistent asthma

Secondary Objectives:

To evaluate the safety and tolerability of dupilumab
To evaluate the effect of dupilumab on improving patient reported outcomes including health related quality of life
To evaluate dupilumab systemic exposure and immunogenicity

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Dupilumab SAR231893 Drug: Placebo Drug: Asthma Controller Therapies (include prednisone/prednisolone) Drug: Asthma Reliever Therapies	Phase 3

Detailed Description

The total duration of study per patient is approximately 40 weeks, including 3 to 5 weeks of screening period, 24 weeks of treatment period and 12 weeks of post-treatment period.

Study Design

Study Type:

Interventional

Actual Enrollment :

486 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double Blind, Placebo-controlled, Parallel-group Phase 3 Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Persistent Asthma

Actual Study Start Date :

Jan 25, 2019

Actual Primary Completion Date :

May 21, 2022

Actual Study Completion Date :

May 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dupilumab For patients without oral corticosteroids (OCS) maintenance therapy, dose 1 of dupilumab administered once in 2 weeks (q2w) with loading dose of dupilumab, two times dose 1; for patients on OCS maintenance therapy, the dose will be dupilumab dose 2 q2w with loading dose 2 times dose 2	Drug: Dupilumab SAR231893 Pharmaceutical form: Solution Route of administration: Subcutaneous Drug: Asthma Controller Therapies (include prednisone/prednisolone) Pharmaceutical form: Aerosol, capsules, tablets, oral solution Route of administration: Inhalation, oral Drug: Asthma Reliever Therapies Pharmaceutical form: Nebulized, aerosol Route of administration: Inhaled
Placebo Comparator: Placebo for dupilumab For patients without OCS maintenance therapy, the patients will take placebo matching to dupilumab dose 1 q2w with loading dose; for patients on OCS maintenance therapy, the patients will take placebo matching to dupilumab dose 2 q2w with loading dose	Drug: Placebo Pharmaceutical form: Solution Route of administration: Subcutaneous Drug: Asthma Controller Therapies (include prednisone/prednisolone) Pharmaceutical form: Aerosol, capsules, tablets, oral solution Route of administration: Inhalation, oral Drug: Asthma Reliever Therapies Pharmaceutical form: Nebulized, aerosol Route of administration: Inhaled

Arm

Intervention/Treatment

Experimental: Dupilumab

For patients without oral corticosteroids (OCS) maintenance therapy, dose 1 of dupilumab administered once in 2 weeks (q2w) with loading dose of dupilumab, two times dose 1; for patients on OCS maintenance therapy, the dose will be dupilumab dose 2 q2w with loading dose 2 times dose 2

Drug: Dupilumab SAR231893

Pharmaceutical form: Solution Route of administration: Subcutaneous

Drug: Asthma Controller Therapies (include prednisone/prednisolone)

Pharmaceutical form: Aerosol, capsules, tablets, oral solution Route of administration: Inhalation, oral

Drug: Asthma Reliever Therapies

Pharmaceutical form: Nebulized, aerosol Route of administration: Inhaled

Placebo Comparator: Placebo for dupilumab

For patients without OCS maintenance therapy, the patients will take placebo matching to dupilumab dose 1 q2w with loading dose; for patients on OCS maintenance therapy, the patients will take placebo matching to dupilumab dose 2 q2w with loading dose

Drug: Placebo

Pharmaceutical form: Solution Route of administration: Subcutaneous

Drug: Asthma Controller Therapies (include prednisone/prednisolone)

Pharmaceutical form: Aerosol, capsules, tablets, oral solution Route of administration: Inhalation, oral

Drug: Asthma Reliever Therapies

Pharmaceutical form: Nebulized, aerosol Route of administration: Inhaled

Outcome Measures

Primary Outcome Measures

Change in pre-bronchodilator forced expiratory volume (FEV1) [Baseline to Week 36]
Absolute change from baseline in pre-bronchodilator FEV1 at Week 36

Secondary Outcome Measures

Annualized rate of severe exacerbation events [During the 24-week placebo-controlled treatment period]
Annualized rate of severe exacerbation events during the 24-week placebo-controlled treatment period
Percent change from baseline in pre-bronchodilator FEV1 [Baseline to Week 12]
Percent change from baseline in pre-bronchodilator FEV1 at Week 12
Annualized rate of loss of asthma control (LOAC) event [During the 24-week placebo-controlled treatment period]
Annualized rate of LOAC event during the 24-week placebo-controlled treatment period
Annualized rate of severe exacerbation events resulting in hospitalization or emergency room visit [During the 24-week placebo-controlled treatment period]
Annualized rate of severe exacerbation events resulting in hospitalization or emergency room visit during the 24-week placebo-controlled treatment period
Time to first severe exacerbation event [During the 24-week placebo-controlled treatment period]
Time to first severe exacerbation event during the 24-week placebo-controlled treatment period
Time to first LOAC [During the 24-week placebo-controlled treatment period]
Time to first LOAC during the 24-week placebo-controlled treatment period
Change from baseline in Asthma Control Questionnaire (ACQ)-5 score [Baseline to Week 24]
Change from baseline in ACQ-5 score at Week 24
Change from baseline in ACQ-7 score [Baseline to Week 24]
Change from baseline in ACQ-7 score at Week 24
Morning/evening asthma symptom score (e-diary) [Baseline to Week 24]
Change from baseline at Week 24 in morning/evening asthma symptom score (e-diary)
Nocturnal awakenings (e-diary) [Baseline to week 24]
Change from baseline at Week 24 in nocturnal awakenings (e-diary)
Use of daily puffs of rescue medication [Baseline to Week 24]
Change from baseline at Week 24 in use of daily puffs of rescue medication
Change from baseline in Asthma Quality of Life Questionnaire (AQLQ) with Standardized Activities (≥12 years) (AQLQ+12) [Baseline to Week 24]
Change from baseline in AQLQ with Standardized Activities (≥12 years) (AQLQ+12) at Week 24
Change from baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) [Baseline to Week 24]
Change from baseline in EQ-5D-5L at Week 24
Assessment of adverse events (AEs) [Baseline to week 36]
Number of participants with adverse events (AEs)

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria :

Adults and adolescent patients (≥12 years of age) with a physician diagnosis of asthma for ≥12 months, based on the Global Initiative for Asthma 2017 Guidelines and the following criteria:
Patients requiring a third controller for their asthma will be considered eligible for this study, and it should also be used for at least 3 months with a stable dose ≥1 month prior to the screening visit (Visit 1).
Patients requiring maintenance oral corticosteroids (OCS) with a stable dose ≤10 mg/day prednisone or equivalent will be allowed; OCS should be used for at least 3 months with a stable dose ≥1 month prior to the screening visit (Visit 1).
Pre-bronchodilator FEV1 ≤ 80% of predicted normal for adults and ≤90% of predicted normal for adolescents at the screening visit and the randomization visit (Visits 1 and 2), prior to randomization.
Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at the screening visit and the randomization visit (Visits 1 and 2), prior to randomization.
For patients not requiring maintenance OCS, screening blood eosinophil count ≥150 cells/μL or Fractional Exhaled Nitric Oxide (FENO) ≥25 parts per billion (ppb); for patients requiring maintenance OCS, there is no minimum requirement for blood eosinophil count and FENO level.

Exclusion criteria:

Patients <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, patient recruitment will be restricted to those who are ≥18 years of age).
Weight is less than 30 kg at the screening visit (Visit 1) or the randomization visit (Visit 2).
Chronic obstructive pulmonary disease or other lung diseases (eg, idiopathic pulmonary fibrosis) which may impair lung function.
A patient who experiences a severe asthma exacerbation (defined as deterioration of asthma that results in emergency treatment, hospitalization due to asthma, treatment with systemic steroids, or treatment with systemic steroid at least twice the previous dose for patients on OCS maintenance) at any time from 1 month prior to the screening visit (Visit 1) up to and including the randomization visit (Visit 2).
Evidence of lung disease(s) other than asthma, either clinical or imaging evidence (eg, chest X-ray, computed tomography, and magnetic resonance imaging) within 3 months prior to the screening visit (Visit 1) as per local standard of care.
Current smoker or cessation of smoking within 6 months prior to the screening visit (Visit 1).
Previous smoker with a smoking history >10 pack-years.
Comorbid disease that might interfere with the evaluation of investigational medicinal product (IMP).

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Investigational Site Number :1560013	Baotou	China	014010
2	Investigational Site Number :1560016	Beijing	China	100020
3	Investigational Site Number :1560029	Beijing	China	100029
4	Investigational Site Number :1560015	Beijing	China	100034
5	Investigational Site Number :1560056	Beijing	China
6	Investigational Site Number :1560057	Changchun	China	130041
7	Investigational Site Number :1560010	Changsha	China	410013
8	Investigational Site Number :1560030	Chengdu	China	610041
9	Investigational Site Number :1560053	Chengdu	China
10	Investigational Site Number :1560025	Chongqing	China	400038
11	Investigational Site Number :1560004	Guangzhou	China	510080
12	Investigational Site Number :1560001	Guangzhou	China	510120
13	Investigational Site Number :1560045	Guangzhou	China	510150
14	Investigational Site Number :1560032	Guiyang	China	550002
15	Investigational Site Number :1560019	Hangzhou	China	310003
16	Investigational Site Number :1560007	Hangzhou	China	310006
17	Investigational Site Number :1560014	Hangzhou	China	310009
18	Investigational Site Number :1560026	Hangzhou	China	310016
19	Investigational Site Number :1560043	Hangzhou	China
20	Investigational Site Number :1560038	Hefei	China
21	Investigational Site Number :1560044	Hohhot	China	010017
22	Investigational Site Number :1560008	Hohhot	China	010050
23	Investigational Site Number :1560022	Lanzhou	China	730000
24	Investigational Site Number :1560024	Nanchang	China	330006
25	Investigational Site Number :1560051	Nanjing	China	210005
26	Investigational Site Number :1560054	Nanjing	China	210006
27	Investigational Site Number :1560037	Nanjing	China	210029
28	Investigational Site Number :1560035	Pingxiang	China	337055
29	Investigational Site Number :1560050	Shanghai	China	200025
30	Investigational Site Number :1560049	Shanghai	China	200030
31	Investigational Site Number :1560005	Shanghai	China	200032
32	Investigational Site Number :1560011	Shanghai	China	200080
33	Investigational Site Number :1560017	Shanghai	China	200120
34	Investigational Site Number :1560006	Shanghai	China	200233
35	Investigational Site Number :1560002	Shanghai	China	200433
36	Investigational Site Number :1560018	Shenyang	China	110001
37	Investigational Site Number :1560036	Shenyang	China	110004
38	Investigational Site Number :1560012	Shenzhen	China	518020
39	Investigational Site Number :1560042	Shenzhen	China	518102
40	Investigational Site Number :1560003	Shijiazhuang	China	050000
41	Investigational Site Number :1560041	Shijiazhuang	China	050041
42	Investigational Site Number :1560031	Suzhou	China	215006
43	Investigational Site Number :1560048	Taiyuan	China	030001
44	Investigational Site Number :1560020	Tianjin	China	300052
45	Investigational Site Number :1560033	Urumchi	China	830054
46	Investigational Site Number :1560021	Wenzhou	China	325000
47	Investigational Site Number :1560052	Wuhan	China	430000
48	Investigational Site Number :1560028	Wuhan	China	430030
49	Investigational Site Number :1560040	Xi'an	China
50	Investigational Site Number :1560046	Xiamen	China	361004
51	Investigational Site Number :1560027	Xiangtan	China
52	Investigational Site Number :1560023	Xuzhou	China	221002
53	Investigational Site Number :1560055	Yangzhou	China	225001
54	Investigational Site Number :1560047	Zhanjiang	China	524001
55	Investigational Site Number :3560006	Chandigarh	India	160012
56	Investigational Site Number :3560002	Coimbatore	India	641028
57	Investigational Site Number :3560013	Hyderabad	India	500082
58	Investigational Site Number :3560005	Jaipur	India	302023
59	Investigational Site Number :3560015	Jaipur	India	302039
60	Investigational Site Number :3560010	Kolkata	India	700107
61	Investigational Site Number :3560011	Kozhikode	India	673008
62	Investigational Site Number :3560012	Mohali	India	160062
63	Investigational Site Number :3560003	Nagpur	India	440012
64	Investigational Site Number :3560016	Nagpur	India	440012
65	Investigational Site Number :3560001	New Delhi	India	110060
66	Investigational Site Number :3560009	Pune	India	411001
67	Investigational Site Number :3560007	Vellore	India	632004

Sponsors and Collaborators

Sanofi
Regeneron Pharmaceuticals

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT03782532

Other Study ID Numbers:

EFC13995
U1111-1175-0772

First Posted:

Dec 20, 2018

Last Update Posted:

Jun 6, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Asthma

Prednisone

Prednisolone

Study Results

No Results Posted as of Jun 6, 2022