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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01312961
• Other study ID #: ACT11457
• Secondary ID: U1111-1117-7826
• Status: Completed
• Phase: Phase 2
• First received: March 9, 2011
• Last updated: June 7, 2017
• Start date: March 2011
• Est. completion date: October 2012

Study information

• Verified date: June 2017
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Pulmonary Eosinophilia

Intervention

Drug:
• Dupilumab
Solution for injection, one subcutaneous injection.
• Placebo (for Dupilumab)
Solution for injection, one subcutaneous injection.
• Fluticasone/Salmeterol combination therapy
Oral inhalation twice daily.
• Fluticasone monotherapy
Oral inhalation twice daily.
• Albuterol
Oral inhalation as needed.
• Levalbuterol
Oral inhalation as needed.

Locations

Country	Name	City	State
United States	Investigational Site Number 840047	Anaheim	California
United States	Investigational Site Number 840014	Baltimore	Maryland
United States	Investigational Site Number 840022	Bozeman	Montana
United States	Investigational Site Number 840027	Charleston	South Carolina
United States	Investigational Site Number 840031	Colorado Springs	Colorado
United States	Investigational Site Number 840011	Denver	Colorado
United States	Investigational Site Number 840017	Denver	Colorado
United States	Investigational Site Number 840030	El Paso	Texas
United States	Investigational Site Number 840040	Hershey	Pennsylvania
United States	Investigational Site Number 840028	Indianapolis	Indiana
United States	Investigational Site Number 840038	Iowa City	Iowa
United States	Investigational Site Number 840001	Lake Oswego	Oregon
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 840034	Madison	Wisconsin
United States	Investigational Site Number 840012	Medford	Oregon
United States	Investigational Site Number 840003	Minneapolis	Minnesota
United States	Investigational Site Number 840010	Minneapolis	Minnesota
United States	Investigational Site Number 840005	Mission Viejo	California
United States	Investigational Site Number 840026	New Haven	Connecticut
United States	Investigational Site Number 840015	North Dartmouth	Massachusetts
United States	Investigational Site Number 840045	Oklahoma City	Oklahoma
United States	Investigational Site Number 840025	Omaha	Nebraska
United States	Investigational Site Number 840007	Orange	California
United States	Investigational Site Number 840021	Overland Park	Kansas
United States	Investigational Site Number 840053	Owensboro	Kentucky
United States	Investigational Site Number 840008	Papillion	Nebraska
United States	Investigational Site Number 840037	Pittsburgh	Pennsylvania
United States	Investigational Site Number 840016	Portland	Oregon
United States	Investigational Site Number 840018	Princeton	New Jersey
United States	Investigational Site Number 840049	Richmond	Virginia
United States	Investigational Site Number 840048	Riverside	California
United States	Investigational Site Number 840035	Rolling Hills Estates	California
United States	Investigational Site Number 840006	Saint Louis	Missouri
United States	Investigational Site Number 840013	Saint Louis	Missouri
United States	Investigational Site Number 840050	San Antonio	Texas
United States	Investigational Site Number 840041	San Francisco	California
United States	Investigational Site Number 840042	San Francisco	California
United States	Investigational Site Number 840039	San Jose	California
United States	Investigational Site Number 840024	Santa Rosa	California
United States	Investigational Site Number 840020	Seattle	Washington
United States	Investigational Site Number 840052	South Burlington	Vermont
United States	Investigational Site Number 840002	Stockton	California
United States	Investigational Site Number 840023	Sylvania	Ohio
United States	Investigational Site Number 840019	Tacoma	Washington
United States	Investigational Site Number 840044	Tallahassee	Florida
United States	Investigational Site Number 840029	Tampa	Florida
United States	Investigational Site Number 840009	Upland	Pennsylvania
United States	Investigational Site Number 840004	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 M — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Asthma Exacerbation	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.	Baseline up to Week 12
Secondary	Time to First Asthma Exacerbation: Kaplan-Meier Estimates at Week 4, Week 8 and 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.	Baseline up to Week 12
Secondary	Percentage of Participants With Composite Asthma Events	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.	Baseline up to Week 12
Secondary	Change From Baseline in Forced Expiratory Flow in One Second (FEV1) to Week 12	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.	Baseline, Week 12
Secondary	Change From Baseline in Peak Expiratory Flow (PEF) to 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.	Baseline, Week 12
Secondary	Change From Baseline in Asthma Control Questionnaire (5-question Version [ACQ-5]) to 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.	Baseline, Week 12
Secondary	Change From Baseline in 22-item Sinonasal Outcome Test (SNOT-22) Score to 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.	Baseline, Week 12
Secondary	Change From Baseline in Morning Asthma Symptom Scores to 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.	Baseline, Week 12
Secondary	Change From Baseline in Evening Asthma Symptom Scores to 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.	Baseline, Week 12
Secondary	Change From Baseline in Number of Nocturnal Awakenings Per Day to 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.	Baseline, Week 12
Secondary	Change From Baseline in Number of Inhalations Per Day of Albuterol or Levalbuterol to 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.	Baseline, Week 12