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

Asthma Clinical Trial

— EXPEDITION  

Official title:

An Exploratory, Double-blind, Placebo-controlled Study of the Effects of Dupilumab on Airway Inflammation of Adults With Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02573233
• Other study ID #: PDY14192
• Secondary ID: 2015-001572-22U1
• Status: Completed
• Phase: Phase 2
• Start date: January 27, 2016
• Est. completion date: January 3, 2018

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: January 3, 2018
• Est. primary completion date: January 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Inflammation

Intervention

Drug:
• Placebo
Pharmaceutical form:solution Route of administration: subcutaneous
• Dupilumab SAR231893/REGN668
Pharmaceutical form:solution Route of administration: subcutaneous
• fluticasone propionate and salmeterol
Pharmaceutical form:inhalation aerosol, inhalation powder Route of administration: inhaled
• budesonide and formoterol
Pharmaceutical form:inhalation aerosol Route of administration: inhaled
• mometasone furoate and formoterol
Pharmaceutical form:inhalation aerosol Route of administration: inhaled

Locations

Country	Name	City	State
Canada	Investigational Site Number 124012	Montreal
Canada	Investigational Site Number 124018	Sainte Foy
Denmark	Investigational Site Number 208002	Hvidovre
Denmark	Investigational Site Number 208001	København Nv
Germany	Investigational Site Number 276013	Frankfurt Am Main
Germany	Investigational Site Number 276011	Großhansdorf
Germany	Investigational Site Number 276012	Hannover
Sweden	Investigational Site Number 752001	Lund
United Kingdom	Investigational Site Number 826010	London
United Kingdom	Investigational Site Number 826009	Oxford
United States	Investigational Site Number 840401	Boston	Massachusetts
United States	Investigational Site Number 840403	Denver	Colorado
United States	Investigational Site Number 840028	Pittsburgh	Pennsylvania
United States	Investigational Site Number 840002	Saint Louis	Missouri
United States	Investigational Site Number 840402	Tucson	Arizona
United States	Investigational Site Number 840404	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Germany,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Week 12
Primary	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.	Baseline, Week 12
Primary	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.	Baseline, Week 12
Primary	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.	Baseline, Week 12
Primary	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.	Baseline, Week 12
Primary	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.	Baseline, Week 12
Secondary	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.	Baseline, Week 12
Secondary	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.	From Baseline to Week 6 through Week 12
Secondary	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.	From Baseline up to 24 weeks
Secondary	Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration	Serum functional dupilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method.	Week 0, Week 2, 6, 8, 12, 18, End of study (Week 24)
Secondary	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.	Baseline up to Week 24