Efficacy, Safety, and Tolerability of Dupilumab in Patients With Persistent Moderate to Severe Eosinophilic Asthma
- Conditions
- Asthma
- Interventions
- Drug: Placebo (for Dupilumab)Drug: Fluticasone/Salmeterol combination therapy
- Registration Number
- NCT01312961
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To investigate the effects of Dupilumab (SAR231893/REGN668) administered subcutaneously (SC) once weekly (qw) for 12 weeks as compared to placebo on reducing the incidence of asthma exacerbation in participants with persistent moderate to severe eosinophilic asthma.
Secondary Objectives:
* To assess the safety and tolerability of Dupilumab administered SC qw for 12 weeks in participants with persistent moderate to severe eosinophilic asthma.
* To assess Dupilumab serum concentrations following qw SC dosing for 12 weeks in participants with persistent moderate to severe eosinophilic asthma.
- Detailed Description
The total duration of the study period per participant was 20-22 weeks broken down as follows:
* Screening period: up to 14 days,
* Treatment period: 12 weeks,
* Follow-up period: 6-8 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 104
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dupilumab 300 mg qw Fluticasone/Salmeterol combination therapy 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. Dupilumab 300 mg qw Fluticasone monotherapy 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. Placebo (for Dupilumab) Fluticasone monotherapy Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of inhaled corticosteroids/long-acting beta2-adrenergic agonist (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. Placebo (for Dupilumab) Placebo (for Dupilumab) Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of inhaled corticosteroids/long-acting beta2-adrenergic agonist (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. Placebo (for Dupilumab) Fluticasone/Salmeterol combination therapy Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of inhaled corticosteroids/long-acting beta2-adrenergic agonist (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. Placebo (for Dupilumab) Levalbuterol Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of inhaled corticosteroids/long-acting beta2-adrenergic agonist (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. Placebo (for Dupilumab) Albuterol Placebo (for Dupilumab) subcutaneous (SC) injection once weekly (qw) for 12 weeks added to background therapy of inhaled corticosteroids/long-acting beta2-adrenergic agonist (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 Dupilumab 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. Dupilumab 300 mg qw Albuterol 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. Dupilumab 300 mg qw Levalbuterol 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Asthma Exacerbation Baseline up to Week 12 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Number of Nocturnal Awakenings Per Day to Week 12 Baseline, Week 12 Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night.
Change From Baseline in Number of Inhalations Per Day of Albuterol or Levalbuterol to Week 12 Baseline, Week 12 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.
Change From Baseline in Peak Expiratory Flow (PEF) to Week 12 Baseline, Week 12 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.
Change From Baseline in Morning Asthma Symptom Scores to Week 12 Baseline, Week 12 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.
Percentage of Participants With Composite Asthma Events Baseline up to Week 12 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.
Change From Baseline in 22-item Sinonasal Outcome Test (SNOT-22) Score to Week 12 Baseline, Week 12 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.
Change From Baseline in Evening Asthma Symptom Scores to Week 12 Baseline, Week 12 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.
Time to First Asthma Exacerbation: Kaplan-Meier Estimates at Week 4, Week 8 and Week 12 Baseline up to Week 12 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.
Change From Baseline in Forced Expiratory Flow in One Second (FEV1) to Week 12 Baseline, Week 12 FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.
Change From Baseline in Asthma Control Questionnaire (5-question Version [ACQ-5]) to Week 12 Baseline, Week 12 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.
Trial Locations
- Locations (50)
Investigational Site Number 840003
🇺🇸Minneapolis, Minnesota, United States
Investigational Site Number 840006
🇺🇸Saint Louis, Missouri, United States
Investigational Site Number 840047
🇺🇸Anaheim, California, United States
Investigational Site Number 840046
🇺🇸Long Beach, California, United States
Investigational Site Number 840032
🇺🇸Los Angeles, California, United States
Investigational Site Number 840036
🇺🇸Los Angeles, California, United States
Investigational Site Number 840005
🇺🇸Mission Viejo, California, United States
Investigational Site Number 840041
🇺🇸San Francisco, California, United States
Investigational Site Number 840048
🇺🇸Riverside, California, United States
Investigational Site Number 840042
🇺🇸San Francisco, California, United States
Investigational Site Number 840007
🇺🇸Orange, California, United States
Investigational Site Number 840035
🇺🇸Rolling Hills Estates, California, United States
Investigational Site Number 840039
🇺🇸San Jose, California, United States
Investigational Site Number 840024
🇺🇸Santa Rosa, California, United States
Investigational Site Number 840002
🇺🇸Stockton, California, United States
Investigational Site Number 840017
🇺🇸Denver, Colorado, United States
Investigational Site Number 840026
🇺🇸New Haven, Connecticut, United States
Investigational Site Number 840028
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840038
🇺🇸Iowa City, Iowa, United States
Investigational Site Number 840053
🇺🇸Owensboro, Kentucky, United States
Investigational Site Number 840014
🇺🇸Baltimore, Maryland, United States
Investigational Site Number 840022
🇺🇸Bozeman, Montana, United States
Investigational Site Number 840013
🇺🇸Saint Louis, Missouri, United States
Investigational Site Number 840008
🇺🇸Papillion, Nebraska, United States
Investigational Site Number 840018
🇺🇸Princeton, New Jersey, United States
Investigational Site Number 840004
🇺🇸Winston-Salem, North Carolina, United States
Investigational Site Number 840023
🇺🇸Sylvania, Ohio, United States
Investigational Site Number 840045
🇺🇸Oklahoma City, Oklahoma, United States
Investigational Site Number 840040
🇺🇸Hershey, Pennsylvania, United States
Investigational Site Number 840037
🇺🇸Pittsburgh, Pennsylvania, United States
Investigational Site Number 840009
🇺🇸Upland, Pennsylvania, United States
Investigational Site Number 840030
🇺🇸El Paso, Texas, United States
Investigational Site Number 840049
🇺🇸Richmond, Virginia, United States
Investigational Site Number 840052
🇺🇸South Burlington, Vermont, United States
Investigational Site Number 840050
🇺🇸San Antonio, Texas, United States
Investigational Site Number 840020
🇺🇸Seattle, Washington, United States
Investigational Site Number 840019
🇺🇸Tacoma, Washington, United States
Investigational Site Number 840029
🇺🇸Tampa, Florida, United States
Investigational Site Number 840044
🇺🇸Tallahassee, Florida, United States
Investigational Site Number 840015
🇺🇸North Dartmouth, Massachusetts, United States
Investigational Site Number 840012
🇺🇸Medford, Oregon, United States
Investigational Site Number 840025
🇺🇸Omaha, Nebraska, United States
Investigational Site Number 840016
🇺🇸Portland, Oregon, United States
Investigational Site Number 840027
🇺🇸Charleston, South Carolina, United States
Investigational Site Number 840034
🇺🇸Madison, Wisconsin, United States
Investigational Site Number 840001
🇺🇸Lake Oswego, Oregon, United States
Investigational Site Number 840010
🇺🇸Minneapolis, Minnesota, United States
Investigational Site Number 840031
🇺🇸Colorado Springs, Colorado, United States
Investigational Site Number 840011
🇺🇸Denver, Colorado, United States
Investigational Site Number 840021
🇺🇸Overland Park, Kansas, United States