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Efficacy, Safety, and Tolerability of Dupilumab in Patients With Persistent Moderate to Severe Eosinophilic Asthma

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01312961
First received: March 9, 2011
Last updated: June 7, 2017
Last verified: June 2017
March 9, 2011
June 7, 2017
March 2011
October 2012   (Final data collection date for primary outcome measure)
Percentage of Participants With Asthma Exacerbation [ Time Frame: 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.
Number of patients experiencing an asthma exacerbation [ Time Frame: 12 weeks ]
Complete list of historical versions of study NCT01312961 on ClinicalTrials.gov Archive Site
  • Time to First Asthma Exacerbation: Kaplan-Meier Estimates at Week 4, Week 8 and Week 12 [ Time Frame: 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.
  • Percentage of Participants With Composite Asthma Events [ Time Frame: 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 Forced Expiratory Flow in One Second (FEV1) to Week 12 [ Time Frame: 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 Peak Expiratory Flow (PEF) to Week 12 [ Time Frame: 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 Asthma Control Questionnaire (5-question Version [ACQ-5]) to Week 12 [ Time Frame: 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.
  • Change From Baseline in 22-item Sinonasal Outcome Test (SNOT-22) Score to Week 12 [ Time Frame: 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 Morning Asthma Symptom Scores to Week 12 [ Time Frame: 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.
  • Change From Baseline in Evening Asthma Symptom Scores to Week 12 [ Time Frame: 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.
  • Change From Baseline in Number of Nocturnal Awakenings Per Day to Week 12 [ Time Frame: 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 [ Time Frame: 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.
  • Time to asthma exacerbation [ Time Frame: 12 weeks ]
  • Change from baseline in Forced Expiratory Flow in 1 second (FEV1) [ Time Frame: 12 weeks ]
  • Change from baseline in Peak Expiratory Flow (PEF) [ Time Frame: 12 weeks ]
  • Change from baseline in the Juniper Asthma Control Questionnaire (Juniper ACQ - 5-question version) score [ Time Frame: 12 weeks ]
  • Change from baseline in 22-item Sinonasal Outcome Test (SNOT-22) score [ Time Frame: 12 weeks ]
  • Change from baseline in the number of Albuterol inhalation per day [ Time Frame: 12 weeks ]
  • Pharmacokinetic (PK) profile of SAR231893 (REGN668): maximum concentration (Cmax), time to Cmax (tmax), area under concentration curve (AUC0-τ) [ Time Frame: 18 weeks ]
Not Provided
Not Provided
 
Efficacy, Safety, and Tolerability of Dupilumab in Patients With Persistent Moderate to Severe Eosinophilic Asthma
Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety, and Tolerability of SAR231893/REGN668 Administered Subcutaneously Once Weekly for 12 Weeks in Patients With Persistent Moderate to Severe Eosinophilic Asthma Who Are Partially Controlled/Uncontrolled by Inhaled Corticosteroid Plus Long-acting beta2 Agonist Therapy

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.

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.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Treatment
Asthma
  • Drug: Dupilumab
    Solution for injection, one subcutaneous injection.
    Other Names:
    • SAR231893
    • REGN668
  • Drug: Placebo (for Dupilumab)
    Solution for injection, one subcutaneous injection.
  • Drug: Fluticasone/Salmeterol combination therapy
    Oral inhalation twice daily.
  • Drug: Fluticasone monotherapy
    Oral inhalation twice daily.
  • Drug: Albuterol
    Oral inhalation as needed.
  • Drug: Levalbuterol
    Oral inhalation as needed.
  • Placebo Comparator: 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.
    Interventions:
    • Drug: Placebo (for Dupilumab)
    • Drug: Fluticasone/Salmeterol combination therapy
    • Drug: Fluticasone monotherapy
    • Drug: Albuterol
    • Drug: Levalbuterol
  • Experimental: Dupilumab 300 mg qw
    Dupilumab 300 mg SC injection qw for 12 weeks added to background therapy of ICS/LABA (Fluticasone/Salmeterol combination therapy at stable dose for 4 weeks followed by Fluticasone monotherapy, dose progressively decreased and discontinued at Week 9). Albuterol or Levalbuterol was given as rescue medication.
    Interventions:
    • Drug: Dupilumab
    • Drug: Fluticasone/Salmeterol combination therapy
    • Drug: Fluticasone monotherapy
    • Drug: Albuterol
    • Drug: Levalbuterol
Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013 Jun 27;368(26):2455-66. doi: 10.1056/NEJMoa1304048. Epub 2013 May 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
104
October 2012
October 2012   (Final data collection date for primary outcome measure)

Inclusion criteria:

Medical diagnosis of persistent asthma for at least 12 months whose:

  • airway inflammation likely to be eosinophilic,
  • asthma partially controlled or uncontrolled on ICS plus LABA therapy.
  • On a stable dose of either Fluticasone/Salmeterol, Budesonide/Formoterol, Mometasone/Formoterol combination therapy for at least 1 month prior to screening.
  • Signed an Informed Consent Form and Health Insurance Portability and Accountability Act (HIPAA) Authorization Form.

Exclusion criteria:

  • Less than 18 years or greater than 65 years of age.
  • Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further evaluation.
  • Chronic obstructive pulmonary disease and/or other lung diseases impairing Pulmonary Function Tests.
  • Beta-adrenergic receptor blockers required for any reason.
  • Current smoker or cessation of smoking within the 6 months prior to screening.
  • Previous smoking with a smoking history >10 cigarette pack/years.
  • Participation in another study within 6 months prior to screening if the study medication was an antibody or within 30 days prior to screening for all other study medications.
  • Known or suspected non-compliance, alcohol or drug abuse.
  • Inability to follow the procedures of the study (e.g, due to language problems, psychological disorders).
  • Concomitant severe diseases or diseases for which the use of ICS or LABA were contraindicated.
  • Known allergy to doxycycline or related compounds.
  • Pregnancy or intention to become pregnant during the course of the study, breast feeding, or unwillingness to use a highly effective method of contraception throughout the study in women of childbearing potential.
  • Recent history of a parasitic infection or travel to a parasitic endemic area within 6 months prior to screening.

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

Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01312961
ACT11457
U1111-1117-7826 ( Other Identifier: UTN )
Yes
Not Provided
Not Provided
Sanofi
Sanofi
Regeneron Pharmaceuticals
Study Director: Clinical Sciences & Operations Sanofi
Sanofi
June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP