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

NCT01312961 | Completed Phase 2 Results DMC

• 2 other identifiers: ACT11457U1111-1117-7826
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 50

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Time to First Asthma Exacerbation: Kaplan-Meier Estimates at Week 4, Week 8 and Week 12

  Baseline up to Week 12

• Percentage of Participants With Composite Asthma Events

  Baseline up to Week 12

• Change From Baseline in Forced Expiratory Flow in One Second (FEV1) to Week 12

  Baseline, Week 12

• Change From Baseline in Peak Expiratory Flow (PEF) to Week 12

  Baseline, Week 12

• Change From Baseline in Asthma Control Questionnaire (5-question Version [ACQ-5]) to Week 12

  Baseline, Week 12

Study Arms (2)

Placebo (for Dupilumab)

PLACEBO COMPARATOR

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.

Drug: Placebo (for Dupilumab); Drug: Fluticasone/Salmeterol combination therapy; Drug: Fluticasone monotherapy; Drug: Albuterol; Drug: Levalbuterol

Dupilumab 300 mg qw

EXPERIMENTAL

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.

Drug: Dupilumab; Drug: Fluticasone/Salmeterol combination therapy; Drug: Fluticasone monotherapy; Drug: Albuterol; Drug: Levalbuterol

Interventions

Dupilumab DRUG

Solution for injection, one subcutaneous injection.

Also known as: SAR231893, REGN668

Dupilumab 300 mg qw

Placebo (for Dupilumab) DRUG

Solution for injection, one subcutaneous injection.

Placebo (for Dupilumab)

Fluticasone/Salmeterol combination therapy DRUG

Oral inhalation twice daily.

Dupilumab 300 mg qw; Placebo (for Dupilumab)

Fluticasone monotherapy DRUG

Oral inhalation twice daily.

Dupilumab 300 mg qw; Placebo (for Dupilumab)

Albuterol DRUG

Oral inhalation as needed.

Dupilumab 300 mg qw; Placebo (for Dupilumab)

Levalbuterol DRUG

Oral inhalation as needed.

Dupilumab 300 mg qw; Placebo (for Dupilumab)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (50)

Investigational Site Number 840047

Anaheim, California, 92804, United States

Location

Investigational Site Number 840046

Long Beach, California, 90806, United States

Location

Investigational Site Number 840032

Los Angeles, California, 90025, United States

Location

Investigational Site Number 840036

Los Angeles, California, 90048, United States

Location

Investigational Site Number 840005

Mission Viejo, California, 92691, United States

Location

Investigational Site Number 840007

Orange, California, 92868, United States

Location

Investigational Site Number 840048

Riverside, California, 92506, United States

Location

Investigational Site Number 840035

Rolling Hills Estates, California, 90274, United States

Location

Investigational Site Number 840041

San Francisco, California, 94143, United States

Location

Investigational Site Number 840042

San Francisco, California, 94143, United States

Location

Investigational Site Number 840039

San Jose, California, 95117, United States

Location

Investigational Site Number 840024

Santa Rosa, California, 95405, United States

Location

Investigational Site Number 840002

Stockton, California, 95207, United States

Location

Investigational Site Number 840031

Colorado Springs, Colorado, 80907, United States

Location

Investigational Site Number 840011

Denver, Colorado, 80206, United States

Location

Investigational Site Number 840017

Denver, Colorado, 80230, United States

Location

Investigational Site Number 840026

New Haven, Connecticut, 06510, United States

Location

Investigational Site Number 840044

Tallahassee, Florida, 32308, United States

Location

Investigational Site Number 840029

Tampa, Florida, 33612, United States

Location

Investigational Site Number 840028

Indianapolis, Indiana, 46208, United States

Location

Investigational Site Number 840038

Iowa City, Iowa, 52240, United States

Location

Investigational Site Number 840021

Overland Park, Kansas, 66210, United States

Location

Investigational Site Number 840053

Owensboro, Kentucky, 42303, United States

Location

Investigational Site Number 840014

Baltimore, Maryland, 21287, United States

Location

Investigational Site Number 840015

North Dartmouth, Massachusetts, 02747, United States

Location

Investigational Site Number 840003

Minneapolis, Minnesota, 55402, United States

Location

Investigational Site Number 840010

Minneapolis, Minnesota, 55402, United States

Location

Investigational Site Number 840006

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840013

St Louis, Missouri, 63141, United States

Location

Investigational Site Number 840022

Bozeman, Montana, 59718, United States

Location

Investigational Site Number 840025

Omaha, Nebraska, 68131, United States

Location

Investigational Site Number 840008

Papillion, Nebraska, 27103, United States

Location

Investigational Site Number 840018

Princeton, New Jersey, 08540, United States

Location

Investigational Site Number 840004

Winston-Salem, North Carolina, 27157-1071, United States

Location

Investigational Site Number 840023

Sylvania, Ohio, 43560, United States

Location

Investigational Site Number 840045

Oklahoma City, Oklahoma, 73120, United States

Location

Investigational Site Number 840001

Lake Oswego, Oregon, 97035, United States

Location

Investigational Site Number 840012

Medford, Oregon, 97504, United States

Location

Investigational Site Number 840016

Portland, Oregon, 97209, United States

Location

Investigational Site Number 840040

Hershey, Pennsylvania, 17033, United States

Location

Investigational Site Number 840037

Pittsburgh, Pennsylvania, 15213, United States

Location

Investigational Site Number 840009

Upland, Pennsylvania, 19013, United States

Location

Investigational Site Number 840027

Charleston, South Carolina, 29407, United States

Location

Investigational Site Number 840030

El Paso, Texas, 79902, United States

Location

Investigational Site Number 840050

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 840052

South Burlington, Vermont, 05403, United States

Location

Investigational Site Number 840049

Richmond, Virginia, 23229, United States

Location

Investigational Site Number 840020

Seattle, Washington, 98105, United States

Location

Investigational Site Number 840019

Tacoma, Washington, 98415-0299, United States

Location

Investigational Site Number 840034

Madison, Wisconsin, 53792, United States

Location

Related 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 Med. 2013 Jun 27;368(26):2455-66. doi: 10.1056/NEJMoa1304048. Epub 2013 May 21.

  PMID: 23688323 RESULT

MeSH Terms

Conditions

Asthma

Interventions

dupilumab; Fluticasone; Albuterol; Levalbuterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2011
• First Posted: March 11, 2011
• Study Start: March 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: June 8, 2017
• Results First Posted: June 8, 2017

Record last verified: 2017-06

Locations

US (50)