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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

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.


Condition or disease Intervention/treatment Phase
Asthma Drug: Placebo Drug: Dupilumab SAR231893/REGN668 Drug: fluticasone propionate and salmeterol Drug: budesonide and formoterol Drug: mometasone furoate and formoterol Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: An Exploratory, Double-blind, Placebo-controlled Study of the Effects of Dupilumab on Airway Inflammation of Adults With Persistent Asthma
Actual Study Start Date : January 27, 2016
Actual Primary Completion Date : January 3, 2018
Actual Study Completion Date : January 3, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Dupilumab

Arm Intervention/treatment
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.
Drug: Placebo
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

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.
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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.


  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02573233


Locations
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United States, Arizona
Investigational Site Number 840402
Tucson, Arizona, United States, 85724
United States, Colorado
Investigational Site Number 840403
Denver, Colorado, United States, 80206
United States, Massachusetts
Investigational Site Number 840401
Boston, Massachusetts, United States, 02115
United States, Missouri
Investigational Site Number 840002
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Investigational Site Number 840404
Winston-Salem, North Carolina, United States, 27157-1071
United States, Pennsylvania
Investigational Site Number 840028
Pittsburgh, Pennsylvania, United States, 15213
Canada
Investigational Site Number 124012
Montreal, Canada, H2X 2P4
Investigational Site Number 124018
Sainte Foy, Canada, G1V 4G5
Denmark
Investigational Site Number 208002
Hvidovre, Denmark, 2650
Investigational Site Number 208001
København Nv, Denmark, 2400
Germany
Investigational Site Number 276013
Frankfurt Am Main, Germany, 60596
Investigational Site Number 276011
Großhansdorf, Germany, 22927
Investigational Site Number 276012
Hannover, Germany, 30625
Sweden
Investigational Site Number 752001
Lund, Sweden, 221 85
United Kingdom
Investigational Site Number 826010
London, United Kingdom, W2 1NY
Investigational Site Number 826009
Oxford, United Kingdom, OX3 7LE
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] November 23, 2016
Statistical Analysis Plan  [PDF] April 9, 2018

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02573233    
Other Study ID Numbers: PDY14192
2015-001572-22 ( EudraCT Number )
U1111-1170-7168 ( Other Identifier: UTN )
First Posted: October 9, 2015    Key Record Dates
Results First Posted: January 28, 2019
Last Update Posted: January 28, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Not yet available for request

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Asthma
Inflammation
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes
Fluticasone
Mometasone Furoate
Budesonide
Formoterol Fumarate
Salmeterol Xinafoate
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists