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

Sanofi

Status and phase: Completed; Phase 2

Conditions: Asthma

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01312961

U1111-1117-7826 (Other Identifier)

ACT11457

Details and patient eligibility

About

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.

Full 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.

Enrollment: 104 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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104 participants in 2 patient groups, including a placebo group

Placebo (for Dupilumab)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo (for Dupilumab)

Drug: Albuterol

Drug: Fluticasone monotherapy

Drug: Levalbuterol

Drug: Fluticasone/Salmeterol combination therapy

Dupilumab 300 mg qw

Experimental group

Description:

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.

Treatment:

Drug: Albuterol

Drug: Fluticasone monotherapy

Drug: Dupilumab

Drug: Levalbuterol

Drug: Fluticasone/Salmeterol combination therapy