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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02573233
Recruitment Status : Completed
First Posted : October 9, 2015
Results First Posted : January 28, 2019
Last Update Posted : January 28, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE October 8, 2015
First Posted Date  ICMJE October 9, 2015
Results First Submitted Date  ICMJE December 19, 2018
Results First Posted Date  ICMJE January 28, 2019
Last Update Posted Date January 28, 2019
Actual Study Start Date  ICMJE January 27, 2016
Actual Primary Completion Date January 3, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2019)
  • Change From Baseline in Eosinophils Cells Count in the Bronchial Submucosa at Week 12 [ Time Frame: Baseline, 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 [ Time Frame: Baseline, 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 [ Time Frame: Baseline, 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 [ Time Frame: Baseline, 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 [ Time Frame: Baseline, 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 [ Time Frame: Baseline, 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2015)
  • Change from baseline in number of inflammatory cells in the bronchial submucosa per square millimeter [ Time Frame: Baseline, 12 weeks ]
  • Change from baseline in mucin-stained area in the bronchial submucosa per square millimeter [ Time Frame: Baseline, 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2019)
  • Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12 [ Time Frame: Baseline, 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 [ Time Frame: 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) [ Time Frame: From Baseline up to 24 weeks ]
    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 [ Time Frame: Week 0, Week 2, 6, 8, 12, 18, End of study (Week 24) ]
    Serum functional dupilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Week 24 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2015)
  • Absolute change from baseline in exhaled nitric oxide [ Time Frame: Baseline, 12 weeks ]
  • Proportion of patients with antidrug antibodies [ Time Frame: Up to 24 weeks ]
  • Proportion of patients with adverse events [ Time Frame: Up to 24 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Dupilumab's Effects on Airway Inflammation in Patients With Asthma
Official Title  ICMJE An Exploratory, Double-blind, Placebo-controlled Study of the Effects of Dupilumab on Airway Inflammation of Adults With Persistent Asthma
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: Placebo
    Pharmaceutical form:solution Route of administration: subcutaneous
  • Drug: Dupilumab SAR231893/REGN668
    Pharmaceutical form:solution Route of administration: subcutaneous
  • Drug: fluticasone propionate and salmeterol
    Pharmaceutical form:inhalation aerosol, inhalation powder Route of administration: inhaled
    Other Name: Advair
  • Drug: budesonide and formoterol
    Pharmaceutical form:inhalation aerosol Route of administration: inhaled
    Other Name: Symbicort
  • Drug: mometasone furoate and formoterol
    Pharmaceutical form:inhalation aerosol Route of administration: inhaled
    Other Name: Dulera
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    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.
    Interventions:
    • Drug: Placebo
    • Drug: fluticasone propionate and salmeterol
    • Drug: budesonide and formoterol
    • Drug: mometasone furoate and formoterol
  • Experimental: Dupilumab
    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.
    Interventions:
    • Drug: Dupilumab SAR231893/REGN668
    • Drug: fluticasone propionate and salmeterol
    • Drug: budesonide and formoterol
    • Drug: mometasone furoate and formoterol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 8, 2015)
42
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 3, 2018
Actual Primary Completion Date January 3, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Denmark,   Germany,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02573233
Other Study ID Numbers  ICMJE PDY14192
2015-001572-22 ( EudraCT Number )
U1111-1170-7168 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Not yet available for request
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date January 2019

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