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

NCT02573233 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: PDY141922015-001572-22U1111-1170-7168
• Study Type: interventional
• Target: 42
• Locations: 6 countries
• Sites: 16

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (5)

• Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 12

  Baseline, Week 12

• Average Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 6 Through Week 12

  From Baseline to Week 6 through Week 12

• Number of Participants With Antidrug Antibodies (ADA)

  From Baseline up to 24 weeks

• Pharmacokinetics (PK) Assessment: Serum Functional Dupilumab Concentration

  Week 0, Week 2, 6, 8, 12, 18, End of study (Week 24)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  Baseline up to Week 24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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; Drug: fluticasone propionate and salmeterol; Drug: budesonide and formoterol; Drug: mometasone furoate and formoterol

Dupilumab

EXPERIMENTAL

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; Drug: fluticasone propionate and salmeterol; Drug: budesonide and formoterol; Drug: mometasone furoate and formoterol

Interventions

Placebo DRUG

Pharmaceutical form:solution Route of administration: subcutaneous

Placebo

Dupilumab SAR231893/REGN668 DRUG

Pharmaceutical form:solution Route of administration: subcutaneous

Dupilumab

fluticasone propionate and salmeterol DRUG

Pharmaceutical form:inhalation aerosol, inhalation powder Route of administration: inhaled

Also known as: Advair

Dupilumab; Placebo

budesonide and formoterol DRUG

Pharmaceutical form:inhalation aerosol Route of administration: inhaled

Also known as: Symbicort

Dupilumab; Placebo

mometasone furoate and formoterol DRUG

Pharmaceutical form:inhalation aerosol Route of administration: inhaled

Also known as: Dulera

Dupilumab; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (16)

Investigational Site Number 840402

Tucson, Arizona, 85724, United States

Location

Investigational Site Number 840403

Denver, Colorado, 80206, United States

Location

Investigational Site Number 840401

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number 840002

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840404

Winston-Salem, North Carolina, 27157-1071, United States

Location

Investigational Site Number 840028

Pittsburgh, Pennsylvania, 15213, United States

Location

Investigational Site Number 124012

Montreal, H2X 2P4, Canada

Location

Investigational Site Number 124018

Sainte-Foy, G1V 4G5, Canada

Location

Investigational Site Number 208002

Hvidovre, 2650, Denmark

Location

Investigational Site Number 208001

København NV, 2400, Denmark

Location

Investigational Site Number 276013

Frankfurt am Main, 60596, Germany

Location

Investigational Site Number 276011

Großhansdorf, 22927, Germany

Location

Investigational Site Number 276012

Hanover, 30625, Germany

Location

Investigational Site Number 752001

Lund, 221 85, Sweden

Location

Investigational Site Number 826010

London, W2 1NY, United Kingdom

Location

Investigational Site Number 826009

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

dupilumab; Fluticasone-Salmeterol Drug Combination; Budesonide; Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination; Mometasone Furoate; Mometasone Furoate, Formoterol Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fluticasone; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Pregnenediones; Pregnenes; Pregnanes; Pregnadienediols; Pregnadienes

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2015
• First Posted: October 9, 2015
• Study Start: January 27, 2016
• Primary Completion: January 3, 2018
• Study Completion: January 3, 2018
• Last Updated: April 4, 2022
• Results First Posted: January 28, 2019

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (2); DK (2); CA (2); US (6); SE (1); DE (3)