Efficacy and Safety Study of Dupilumab in Patients With Persistent Asthma

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

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

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: Dupilumab SAR231893; Drug: Asthma Controller Therapies (include prednisone/prednisolone); Drug: Asthma Reliever Therapies

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 Type: Interventional
• Enrollment (Actual): 486
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Baotou, China, 014010
    • Investigational Site Number :1560013
  • Beijing, China, 100020
    • Investigational Site Number :1560016
  • Beijing, China, 100029
    • Investigational Site Number :1560029
  • Beijing, China, 100034
    • Investigational Site Number :1560015
  • Beijing, China
    • Investigational Site Number :1560056
  • Changchun, China, 130041
    • Investigational Site Number :1560057
  • Changsha, China, 410013
    • Investigational Site Number :1560010
  • Chengdu, China, 610041
    • Investigational Site Number :1560030
  • Chengdu, China
    • Investigational Site Number :1560053
  • Chongqing, China, 400038
    • Investigational Site Number :1560025
  • Guangzhou, China, 510080
    • Investigational Site Number :1560004
  • Guangzhou, China, 510120
    • Investigational Site Number :1560001
  • Guangzhou, China, 510150
    • Investigational Site Number :1560045
  • Guiyang, China, 550002
    • Investigational Site Number :1560032
  • Hangzhou, China, 310003
    • Investigational Site Number :1560019
  • Hangzhou, China, 310006
    • Investigational Site Number :1560007
  • Hangzhou, China, 310009
    • Investigational Site Number :1560014
  • Hangzhou, China, 310016
    • Investigational Site Number :1560026
  • Hangzhou, China
    • Investigational Site Number :1560043
  • Hefei, China
    • Investigational Site Number :1560038
  • Hohhot, China, 010050
    • Investigational Site Number :1560008
  • Hohhot, China, 010017
    • Investigational Site Number :1560044
  • Lanzhou, China, 730000
    • Investigational Site Number :1560022
  • Nanchang, China, 330006
    • Investigational Site Number :1560024
  • Nanjing, China, 210005
    • Investigational Site Number :1560051
  • Nanjing, China, 210006
    • Investigational Site Number :1560054
  • Nanjing, China, 210029
    • Investigational Site Number :1560037
  • Pingxiang, China, 337055
    • Investigational Site Number :1560035
  • Shanghai, China, 200025
    • Investigational Site Number :1560050
  • Shanghai, China, 200030
    • Investigational Site Number :1560049
  • Shanghai, China, 200032
    • Investigational Site Number :1560005
  • Shanghai, China, 200080
    • Investigational Site Number :1560011
  • Shanghai, China, 200120
    • Investigational Site Number :1560017
  • Shanghai, China, 200233
    • Investigational Site Number :1560006
  • Shanghai, China, 200433
    • Investigational Site Number :1560002
  • Shenyang, China, 110001
    • Investigational Site Number :1560018
  • Shenyang, China, 110004
    • Investigational Site Number :1560036
  • Shenzhen, China, 518020
    • Investigational Site Number :1560012
  • Shenzhen, China, 518102
    • Investigational Site Number :1560042
  • Shijiazhuang, China, 050000
    • Investigational Site Number :1560003
  • Shijiazhuang, China, 050041
    • Investigational Site Number :1560041
  • Suzhou, China, 215006
    • Investigational Site Number :1560031
  • Taiyuan, China, 030001
    • Investigational Site Number :1560048
  • Tianjin, China, 300052
    • Investigational Site Number :1560020
  • Urumchi, China, 830054
    • Investigational Site Number :1560033
  • Wenzhou, China, 325000
    • Investigational Site Number :1560021
  • Wuhan, China, 430000
    • Investigational Site Number :1560052
  • Wuhan, China, 430030
    • Investigational Site Number :1560028
  • Xi'an, China
    • Investigational Site Number :1560040
  • Xiamen, China, 361004
    • Investigational Site Number :1560046
  • Xiangtan, China
    • Investigational Site Number :1560027
  • Xuzhou, China, 221002
    • Investigational Site Number :1560023
  • Yangzhou, China, 225001
    • Investigational Site Number :1560055
  • Zhanjiang, China, 524001
    • Investigational Site Number :1560047
• India
  • Chandigarh, India, 160012
    • Investigational Site Number :3560006
  • Coimbatore, India, 641028
    • Investigational Site Number :3560002
  • Hyderabad, India, 500082
    • Investigational Site Number :3560013
  • Jaipur, India, 302023
    • Investigational Site Number :3560005
  • Jaipur, India, 302039
    • Investigational Site Number :3560015
  • Kolkata, India, 700107
    • Investigational Site Number :3560010
  • Kozhikode, India, 673008
    • Investigational Site Number :3560011
  • Mohali, India, 160062
    • Investigational Site Number :3560012
  • Nagpur, India, 440012
    • Investigational Site Number :3560003
  • Nagpur, India, 440012
    • Investigational Site Number :3560016
  • New Delhi, India, 110060
    • Investigational Site Number :3560001
  • Pune, India, 411001
    • Investigational Site Number :3560009
  • Vellore, India, 632004
    • Investigational Site Number :3560007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pre-bronchodilator forced expiratory volume (FEV1)	Absolute change from baseline in pre-bronchodilator FEV1 at Week 12	Baseline to Week 12

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• 2022-002375-11 EudraCT results

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2019
• Primary Completion (Actual): May 21, 2022
• Study Completion (Actual): May 21, 2022

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 18, 2018
• First Posted (Actual): December 20, 2018

Study Record Updates

• Last Update Posted (Actual): December 28, 2022
• Last Update Submitted That Met QC Criteria: December 23, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone; Prednisone
• Other Study ID Numbers: EFC13995; U1111-1175-0772 (Other Identifier: UTN); 2022-002375-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No