Evaluation of Dupilumab's Effects on Airway Inflammation in Patients With Asthma
- Conditions
- Asthma
- Interventions
- Registration Number
- NCT02573233
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dupilumab mometasone furoate and formoterol 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. Dupilumab fluticasone propionate and salmeterol 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. Placebo 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. Placebo fluticasone propionate and salmeterol 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. Placebo budesonide and formoterol 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. Placebo mometasone furoate and formoterol 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 Dupilumab SAR231893/REGN668 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. Dupilumab budesonide and formoterol 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Eosinophils Cells Count in the Bronchial Submucosa at Week 12 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 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 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 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-Helper Lymphocytes Count in the Bronchial Submucosa at Week 12 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.
Change From Baseline in T-Lymphocytes Count in the Bronchial Submucosa at Week 12 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12 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 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) 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 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) 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.
Trial Locations
- Locations (16)
Investigational Site Number 124012
šØš¦Montreal, Canada
Investigational Site Number 840028
šŗšøPittsburgh, Pennsylvania, United States
Investigational Site Number 752001
šøšŖLund, Sweden
Investigational Site Number 826010
š¬š§London, United Kingdom
Investigational Site Number 840402
šŗšøTucson, Arizona, United States
Investigational Site Number 840401
šŗšøBoston, Massachusetts, United States
Investigational Site Number 208001
š©š°KĆøbenhavn Nv, Denmark
Investigational Site Number 840403
šŗšøDenver, Colorado, United States
Investigational Site Number 276011
š©šŖGroĆhansdorf, Germany
Investigational Site Number 208002
š©š°Hvidovre, Denmark
Investigational Site Number 276012
š©šŖHannover, Germany
Investigational Site Number 840002
šŗšøSaint Louis, Missouri, United States
Investigational Site Number 124018
šØš¦Sainte Foy, Canada
Investigational Site Number 276013
š©šŖFrankfurt Am Main, Germany
Investigational Site Number 826009
š¬š§Oxford, United Kingdom
Investigational Site Number 840404
šŗšøWinston-Salem, North Carolina, United States