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Evaluation of Dupilumab's Effects on Airway Inflammation in Patients With Asthma (EXPEDITION)

Primary Purpose

Asthma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Dupilumab SAR231893/REGN668
fluticasone propionate and salmeterol
budesonide and formoterol
mometasone furoate and formoterol
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Male and female adults with a physician diagnosis of persistent asthma for ≥12 months.
  • Existing treatment with medium to high dose inhaled corticosteroids in combination with a long-acting beta agonist for at least 3 months with a stable dose ≥1 month prior to Visit 1 (Screening Visit).
  • Treatment with a third asthma controller for at least 3 months with a stable dose >=1 month prior to Visit 1 was allowed.
  • Pre-bronchodilator forced expiratory volume (FEV1) 55 to 85% of predicted normal.

Exclusion criteria:

  • Participants <18 years or >65 years.
  • Fractional exhaled nitric oxide (FeNO) <26 parts per billion (ppb) at Visit 1 (Screening Visit).
  • Chronic obstructive pulmonary disease or other lung diseases (eg, idiopathic pulmonary fibrosis, eosinophilic granulomatosis with polyangiitis [Churg-Strauss Syndrome]) which could impair lung function.
  • A participant who experienced an asthma exacerbation that resulted in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids at any time from 1 month prior to Visit 1.
  • A participant who had experienced an upper or lower respiratory tract infection within the 4 weeks prior to Visit 1.
  • Evidence of lung disease(s) other than asthma.
  • Previous smoker (smoking history >10 pack-years) or current smoker (within 6 months prior to Visit 1).
  • Comorbid disease that might interfere with the evaluation of investigational medicinal product or conduct of study procedures (e.g., bronchoscopy).
  • Anti-immunoglobulin E (IgE) therapy (omalizumab) or any other biologic therapy within 6 months of Visit 1.
  • Exposure to another investigative study medication within a time period prior to Visit 1 that is less than 5 half-lives of the study medication.
  • Treatment with systemic (oral or injectable) corticosteroids within 28 days of Visit 1.

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

Sites / Locations

  • Investigational Site Number 840402
  • Investigational Site Number 840403
  • Investigational Site Number 840401
  • Investigational Site Number 840002
  • Investigational Site Number 840404
  • Investigational Site Number 840028
  • Investigational Site Number 124012
  • Investigational Site Number 124018
  • Investigational Site Number 208002
  • Investigational Site Number 208001
  • Investigational Site Number 276013
  • Investigational Site Number 276011
  • Investigational Site Number 276012
  • Investigational Site Number 752001
  • Investigational Site Number 826010
  • Investigational Site Number 826009

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Dupilumab

Arm Description

Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14, added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14, added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

Outcomes

Primary Outcome Measures

Change From Baseline in Eosinophils Cells Count in the Bronchial Submucosa at Week 12
Inflammatory cells i.e. eosinophils were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Change From Baseline in Mucin-Stained Area in the Bronchial Submucosa at Week 12
Mucin was identified by staining with Alcian-blue periodic acid-Schiff and/or immunostaining for MUC5AC and then the mucin-positive area was measured and expressed per square millimeter.
Change From Baseline in Mast Cells Count (Chymase Positive) in the Bronchial Submucosa at Week 12
Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Change From Baseline in Mast Cells Count (Tryptase Positive) in the Bronchial Submucosa at Week 12
Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Change From Baseline in T-Lymphocytes Count in the Bronchial Submucosa at Week 12
T-Lymphocytes i.e. CD3 positive cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Change From Baseline in T-Helper Lymphocytes Count in the Bronchial Submucosa at Week 12
T-helper i.e. CD4 positive lymphocytes were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.

Secondary Outcome Measures

Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12
FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/second, and reported in ppb.
Average Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 6 Through Week 12
FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/s, and reported in ppb. The average change in FeNO from baseline to Week 6 through Week 12 was calculated as follows: For each participant the change in FeNO from Baseline to Week 6, Week 8, Week 10 and Week 12 was calculated (value at Week X - value at baseline). Subsequently the weekly mean of these 4 "change from baseline" values was determined (Weeks 6, 8, 10 and 12). Using these weekly mean values the overall arithmetic mean and standard deviation of the average change in FeNO from baseline to Week 6 through Week 12 was calculated.
Number of Participants With Antidrug Antibodies (ADA)
Anti-drug antibodies were detected using a validated immunoassay. Incidence of ADA were classified as following: 1) Pre-existing immunoreactivity - an ADA positive response in the assay at baseline with all post treatment ADA results negative or an ADA positive response at baseline with all post treatment ADA responses less than 4-fold over baseline titer levels. 2) Treatment-emergent ADA: an ADA positive response in the assay post first dose, when baseline results were negative or missing. 3) Treatment-boosted ADA: an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive.
Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Serum functional dupilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse event (AE) was defined as any untoward medical occurrence in a participant who received investigational medicinal product (IMP) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during between the first administration of study medication to the end of the 12 week Post-treatment Period. Serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included both serious and non-serious AEs.

Full Information

First Posted
October 8, 2015
Last Updated
March 24, 2022
Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02573233
Brief Title
Evaluation of Dupilumab's Effects on Airway Inflammation in Patients With Asthma
Acronym
EXPEDITION
Official Title
An Exploratory, Double-blind, Placebo-controlled Study of the Effects of Dupilumab on Airway Inflammation of Adults With Persistent Asthma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
January 27, 2016 (Actual)
Primary Completion Date
January 3, 2018 (Actual)
Study Completion Date
January 3, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Primary Objective: To evaluate the effect of dupilumab, compared to placebo, on airway inflammation in participants with persistent asthma. Secondary Objective: To assess the safety, tolerability, and immunogenicity of dupilumab compared to placebo.
Detailed Description
The total study duration for each participant was between approximately 29 and maximum of 30 weeks, consisting of a screening period of 5 weeks and optional up to 7 additional days, a treatment period of 12 weeks, and a post-treatment period of 12 weeks. Participants who completed the treatment period could be eligible to participate in an open-label extension study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (for dupilumab), 2 subcutaneous injections on Day 1 (Week 1) as a loading dose followed by a single injection q2w from Week 2 to Week 14, added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Arm Title
Dupilumab
Arm Type
Experimental
Arm Description
Dupilumab, 2 subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection q2w from Week 2 to Week 14, added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form:solution Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
Dupilumab SAR231893/REGN668
Intervention Description
Pharmaceutical form:solution Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
fluticasone propionate and salmeterol
Other Intervention Name(s)
Advair
Intervention Description
Pharmaceutical form:inhalation aerosol, inhalation powder Route of administration: inhaled
Intervention Type
Drug
Intervention Name(s)
budesonide and formoterol
Other Intervention Name(s)
Symbicort
Intervention Description
Pharmaceutical form:inhalation aerosol Route of administration: inhaled
Intervention Type
Drug
Intervention Name(s)
mometasone furoate and formoterol
Other Intervention Name(s)
Dulera
Intervention Description
Pharmaceutical form:inhalation aerosol Route of administration: inhaled
Primary Outcome Measure Information:
Title
Change From Baseline in Eosinophils Cells Count in the Bronchial Submucosa at Week 12
Description
Inflammatory cells i.e. eosinophils were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Mucin-Stained Area in the Bronchial Submucosa at Week 12
Description
Mucin was identified by staining with Alcian-blue periodic acid-Schiff and/or immunostaining for MUC5AC and then the mucin-positive area was measured and expressed per square millimeter.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Mast Cells Count (Chymase Positive) in the Bronchial Submucosa at Week 12
Description
Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Mast Cells Count (Tryptase Positive) in the Bronchial Submucosa at Week 12
Description
Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time Frame
Baseline, Week 12
Title
Change From Baseline in T-Lymphocytes Count in the Bronchial Submucosa at Week 12
Description
T-Lymphocytes i.e. CD3 positive cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time Frame
Baseline, Week 12
Title
Change From Baseline in T-Helper Lymphocytes Count in the Bronchial Submucosa at Week 12
Description
T-helper i.e. CD4 positive lymphocytes were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12
Description
FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/second, and reported in ppb.
Time Frame
Baseline, Week 12
Title
Average Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 6 Through Week 12
Description
FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/s, and reported in ppb. The average change in FeNO from baseline to Week 6 through Week 12 was calculated as follows: For each participant the change in FeNO from Baseline to Week 6, Week 8, Week 10 and Week 12 was calculated (value at Week X - value at baseline). Subsequently the weekly mean of these 4 "change from baseline" values was determined (Weeks 6, 8, 10 and 12). Using these weekly mean values the overall arithmetic mean and standard deviation of the average change in FeNO from baseline to Week 6 through Week 12 was calculated.
Time Frame
From Baseline to Week 6 through Week 12
Title
Number of Participants With Antidrug Antibodies (ADA)
Description
Anti-drug antibodies were detected using a validated immunoassay. Incidence of ADA were classified as following: 1) Pre-existing immunoreactivity - an ADA positive response in the assay at baseline with all post treatment ADA results negative or an ADA positive response at baseline with all post treatment ADA responses less than 4-fold over baseline titer levels. 2) Treatment-emergent ADA: an ADA positive response in the assay post first dose, when baseline results were negative or missing. 3) Treatment-boosted ADA: an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive.
Time Frame
From Baseline up to 24 weeks
Title
Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration
Description
Serum functional dupilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method.
Time Frame
Week 0, Week 2, 6, 8, 12, 18, End of study (Week 24)
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
Adverse event (AE) was defined as any untoward medical occurrence in a participant who received investigational medicinal product (IMP) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during between the first administration of study medication to the end of the 12 week Post-treatment Period. Serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included both serious and non-serious AEs.
Time Frame
Baseline up to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Male and female adults with a physician diagnosis of persistent asthma for ≥12 months. Existing treatment with medium to high dose inhaled corticosteroids in combination with a long-acting beta agonist for at least 3 months with a stable dose ≥1 month prior to Visit 1 (Screening Visit). Treatment with a third asthma controller for at least 3 months with a stable dose >=1 month prior to Visit 1 was allowed. Pre-bronchodilator forced expiratory volume (FEV1) 55 to 85% of predicted normal. Exclusion criteria: Participants <18 years or >65 years. Fractional exhaled nitric oxide (FeNO) <26 parts per billion (ppb) at Visit 1 (Screening Visit). Chronic obstructive pulmonary disease or other lung diseases (eg, idiopathic pulmonary fibrosis, eosinophilic granulomatosis with polyangiitis [Churg-Strauss Syndrome]) which could impair lung function. A participant who experienced an asthma exacerbation that resulted in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids at any time from 1 month prior to Visit 1. A participant who had experienced an upper or lower respiratory tract infection within the 4 weeks prior to Visit 1. Evidence of lung disease(s) other than asthma. Previous smoker (smoking history >10 pack-years) or current smoker (within 6 months prior to Visit 1). Comorbid disease that might interfere with the evaluation of investigational medicinal product or conduct of study procedures (e.g., bronchoscopy). Anti-immunoglobulin E (IgE) therapy (omalizumab) or any other biologic therapy within 6 months of Visit 1. Exposure to another investigative study medication within a time period prior to Visit 1 that is less than 5 half-lives of the study medication. Treatment with systemic (oral or injectable) corticosteroids within 28 days of Visit 1. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 840402
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Investigational Site Number 840403
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Investigational Site Number 840401
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Investigational Site Number 840002
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Investigational Site Number 840404
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1071
Country
United States
Facility Name
Investigational Site Number 840028
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Investigational Site Number 124012
City
Montreal
ZIP/Postal Code
H2X 2P4
Country
Canada
Facility Name
Investigational Site Number 124018
City
Sainte Foy
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
Investigational Site Number 208002
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
Facility Name
Investigational Site Number 208001
City
København Nv
ZIP/Postal Code
2400
Country
Denmark
Facility Name
Investigational Site Number 276013
City
Frankfurt Am Main
ZIP/Postal Code
60596
Country
Germany
Facility Name
Investigational Site Number 276011
City
Großhansdorf
ZIP/Postal Code
22927
Country
Germany
Facility Name
Investigational Site Number 276012
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Investigational Site Number 752001
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Investigational Site Number 826010
City
London
ZIP/Postal Code
W2 1NY
Country
United Kingdom
Facility Name
Investigational Site Number 826009
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Learn more about this trial

Evaluation of Dupilumab's Effects on Airway Inflammation in Patients With Asthma

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