Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate-to-severe COPD With Type 2 Inflammation (BOREAS)

• ClinicalTrials.gov Identifier: NCT03930732
• Recruitment Status: Completed
• First Posted: April 29, 2019
• Results First Posted: February 28, 2024
• Last Update Posted: February 28, 2024
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

Primary Objective:

To evaluate the efficacy of dupilumab administered every 2 weeks in patients with moderate-or severe Chronic Obstructive Pulmonary Disease (COPD) as measured by

• Annualized rate of acute moderate and severe COPD exacerbation (AECOPD)

Secondary Objectives:

To evaluate the effect of dupilumab administered every 2 weeks on

• Pre-bronchodilator forced expiratory volume in 1 second (FEV1) over 12 weeks compared to placebo
• Health related quality of life, assessed by the change from baseline to Week 52 in the St. George's Respiratory Questionnaire (SGRQ)
• Pre-bronchodilator FEV1 over 52 weeks compared to placebo
• Lung function assessments
• Moderate and severe COPD exacerbations
• To evaluate safety and tolerability
• To evaluate dupilumab systemic exposure and incidence of anti-drug antibodies (ADA)

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Dupilumab SAR231893; Drug: Inhaled Corticosteroid; Drug: Inhaled Long-Acting Beta Agonist; Drug: Inhaled Long-Acting Muscarinic Antagonist; Drug: Placebo	Phase 3

Detailed Description:

Approximately 68 weeks including a 4-week screening period, a 52-week treatment period, and 12 weeks of follow-up.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 939 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) With Type 2 Inflammation
• Actual Study Start Date: April 15, 2019
• Actual Primary Completion Date: February 8, 2023
• Actual Study Completion Date: May 2, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dupilumab; Participants received dupilumab 300 mg administered as SC injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of treatment i.e., at Week 52).	Drug: Dupilumab SAR231893; Pharmaceutical form: Solution for injection Route of administration: Subcutaneous; Other Name: Dupixent; Drug: Inhaled Corticosteroid; Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation; Drug: Inhaled Long-Acting Beta Agonist; Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation; Drug: Inhaled Long-Acting Muscarinic Antagonist; Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation
Placebo Comparator: Placebo; Participants received placebo matched to dupilumab 300 mg as subcutaneous (SC) injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, end of treatment [EOT] visit occurred 2 weeks after last administration of treatment i.e., at Week 52).	Drug: Inhaled Corticosteroid; Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation; Drug: Inhaled Long-Acting Beta Agonist; Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation; Drug: Inhaled Long-Acting Muscarinic Antagonist; Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation; Drug: Placebo; Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Outcome Measures

Primary Outcome Measures :

1. Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-Week Treatment Period [ Time Frame: Baseline (Day 1) to Week 52 ]
   Moderate exacerbations were recorded by the Investigator and defined as acute exacerbation of COPD (AECOPD) that required either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were also recorded by the Investigator and defined as AECOPD requiring hospitalization, or observation for >24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. Events were adjudicated by independent third party.

Secondary Outcome Measures :

1. Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) at Week 12 [ Time Frame: Baseline (Day 1) to Week 12 ]
   The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration.
2. Change From Baseline in Pre-BD FEV1 at Week 52 [ Time Frame: Baseline (Day 1) to Week 52 ]
   The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration.
3. Change From Baseline in Pre-BD FEV1 at Week 12 in Subgroup of Participants With Baseline Fractional Exhaled Nitric Oxide (FeNO) >=20 Parts Per Billion (Ppb) [ Time Frame: Baseline (Day 1) to Week 12 ]
   FeNO is a demonstrated biomarker of type 2 airway inflammation in respiratory diseases. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 milliliter per second (mL/s) and reported in ppb. This assessment was conducted prior to spirometry and following a fast of at least 1 hour.
4. Change From Baseline in Pre-BD FEV1 at Week 52 in Subgroup of Participants With Baseline FeNO >=20 Ppb [ Time Frame: Baseline (Day 1) to Week 52 ]
   FeNO is a demonstrated biomarker of type 2 airway inflammation in respiratory diseases. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/s and reported in ppb. This assessment was conducted prior to spirometry and following a fast of at least 1 hour.
5. Change From Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 [ Time Frame: Baseline (Day 1) to Week 52 ]
   The SGRQ was a 50-item self-administered questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation and rated on electronic diary. Scores by dimension were calculated for 3 domains: symptoms, activity and impacts (psycho-social) as well as a total score. Global and domain scores range from 0 to 100, with 100 representing the worst possible health status and 0 indicating the best possible health status. Higher score indicates worse health status/heath related quality of life.
6. Percentage of Participants With SGRQ Improvement >=4 Points at Week 52 [ Time Frame: Baseline (Day 1) to Week 52 ]
   A responder was defined as a participant with improvement from baseline in SGRQ total score at Week 52 by >=4 points. Participants with improvement <4 points or with missing values were considered as non-responders. The percentage of participants who achieved a clinically meaningful response in SGRQ total score (reduction [improvement] by >=4 points)/responders are reported.
7. Change From Baseline in Evaluating Respiratory Symptoms (E-RS) in COPD (E-RS: COPD) RS-Total Score at Week 52 [ Time Frame: Baseline (Day 1) to Week 52 ]
   The E-RS in COPD scale was a part of the exacerbations of chronic pulmonary disease tool (EXACT). It was a derivative instrument used to measure the effect of treatment on the severity of respiratory symptoms in stable COPD. E-RS: COPD RS-Total Score was derived based on weekly averages of daily assessed 11 respiratory symptom items contained in the 14-item EXACT questionnaire. The RS-Total score represented overall respiratory symptom severity, ranged from 0 to 40. Summation procedure was used to derive the three daily domain scores: 1). RS-Breathlessness (range 0-17), 2) RS-Cough and Sputum (score range 0-11), 3) RS-Chest Symptoms (score range 0-12). The higher the score, more severe were the symptoms.
8. Annualized Rate of Moderate or Severe COPD Exacerbation Over the 52-Week Treatment Period in Subgroup of Participants With Baseline FeNO >=20 Ppb [ Time Frame: Baseline (Day 1) to Week 52 ]
   Moderate exacerbations were recorded by the Investigator and defined as AECOPD that required either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were also recorded by the investigator and defined as AECOPD requiring hospitalization, or observation for >24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate among participants with baseline FeNO >=20 ppb was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. Events were adjudicated by independent third party.
9. Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 [ Time Frame: Baseline (Day 1) to Weeks 2, 4, 8, 24, 36 and 44 ]
   The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration.
10. Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 [ Time Frame: Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36 and 52 ]
    The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Post-BD FEV1 referred to the spirometry performed within 30 minutes after administration of bronchodilator.
11. Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52 [ Time Frame: Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36, 44 and 52 ]
    FEF is the amount of air (in liters) which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Spirometry was performed after a wash out period of bronchodilators according to their action duration.
12. Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 [ Time Frame: Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36 and 52 ]
    FEF is the amount of air (in liters) which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Spirometry was performed after a wash out period of bronchodilators according to their action duration.
13. Annualized Rate of Severe COPD Exacerbations Over the 52-Week Treatment Period [ Time Frame: Baseline (Day 1) to Week 52 ]
    Moderate exacerbations were recorded by the Investigator and defined as AECOPD that required either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were also recorded by the Investigator and defined as AECOPD requiring hospitalization, or observation for >24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. Events were adjudicated by independent third party.
14. Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period [ Time Frame: Baseline (Day 1) and up to Weeks 12, 24, 36 and 52 ]
    The time to first moderate or severe exacerbation was defined as date of the first event minus randomization date +1. The median time to first severe exacerbation was derived from Cox regression model. Moderate exacerbations events were recorded by the investigator and defined as AECOPD that require either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were recorded by the Investigator and defined as AECOPD requiring hospitalization, or observation for >24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days.
15. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: TEAEs were collected from the time from the first administration of study treatment to the last administration of the study treatment + 98 days, up to 491 days ]
    An Adverse Event (AE) was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during TE period which was defined as the period from the time of first dose of study treatment until the last visit in the study. Serious adverse events (SAE) were defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
16. Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab [ Time Frame: Up to Week 52 ]
    Number of participants with treatment-emergent response to dupilumab with peak post-baseline titers during the on-treatment period are reported. Treatment-emergent response was defined as a positive response in the ADA assay post first dose, when baseline results were negative or missing. Categories were based on titer values and included: low (Titer <1000); moderate (1000<=Titer<=10,000); and high (Titer >10,000). On-treatment period was defined as last study treatment administration plus 14 days; that is, Week 52.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• Participants with a physician diagnosis of COPD who met the following criteria at screening:

  • Current or former smokers with a smoking history of ≥10 pack-years.
  • Moderate-to-severe COPD (post-bronchodilator FEV1/ forced vital capacity [FVC] ratio <0.70 and post-bronchodilator FEV1 % predicted >30% and ≤70%).
  • Medical Research Council (MRC) Dyspnea Scale grade ≥2.
  • Patient-reported history of signs and symptoms of chronic bronchitis (chronic productive cough) for 3 months in the year up to screening in the absence of other known causes of chronic cough.
  • Documented history of high exacerbation risk defined as exacerbation history of ≥2 moderate or ≥1 severe within the year prior to inclusion. At least one exacerbation should have occurred while the patient was taking inhaled corticosteroid (ICS)/long acting beta agonist (LABA)/long acting muscarinic antagonist (LAMA) (or LABA/LAMA if ICS is contraindicated). Moderate exacerbations were recorded by the investigator and defined as acute exacerbation of COPD (AECOPD) that required either systemic corticosteroids (intramuscular, intravenous, or oral) and/or antibiotics. One of the two required moderate exacerbations had to require the use of systemic corticosteroids. Severe exacerbations were recorded by the investigator and defined as AECOPD requiring hospitalization or observation >24 hours in emergency department/urgent care facility.
  • Background triple therapy (ICS + LABA + LAMA) for 3 months prior to randomization with a stable dose of medication for ≥1 month prior to Visit 1; Double therapy (LABA + LAMA) allowed if ICS was contraindicated.
• Evidence of Type 2 inflammation: Patients with blood eosinophils ≥300 cells/microliter at Visit 1.

Exclusion criteria:

• COPD diagnosis for less than 12 months prior to randomization.
• A current diagnosis of asthma or history of asthma according to the 2018 Global Initiative for Asthma (GINA) guidelines or other accepted guidelines.
• Significant pulmonary disease other than COPD (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome etc) or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
• Cor pulmonale, evidence of right cardiac failure.
• Treatment with oxygen of more than 12 hours per day.
• Hypercapnia requiring Bi-level ventilation.
• AECOPD as defined in inclusion criteria within 4 weeks prior to screening, or during the screening period.
• Respiratory tract infection within 4 weeks prior to screening, or during the screening period.
• History of, or planned pneumonectomy or lung volume reduction surgery. Patients who were participating in the acute phase of a pulmonary rehabilitation program, ie, who started rehabilitation <4 weeks prior to screening (Note: patients in the maintenance phase of a rehabilitation program could be included).
• Diagnosis of α-1 anti-trypsin deficiency.

The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

United States, Alabama

SEC Clinical Research, LLC-Site Number:8400030

Andalusia, Alabama, United States, 36420

Clinical Research Center of Alabama, LLC-Site Number:8400041

Birmingham, Alabama, United States, 35209-6802

UAB Lung Health Center-Site Number:8400013

Birmingham, Alabama, United States, 35294

SEC Clinical Research, LLC-Site Number:8400059

Dothan, Alabama, United States, 36303

Pulmonary Associates of Mobile, P.C.-Site Number:8400057

Mobile, Alabama, United States, 36608

United States, Colorado

Asthma and Allergy Associates, PC-Site Number:8400034

Colorado Springs, Colorado, United States, 80907

United States, Florida

Clinical Research Of West Florida Inc-Site Number:8400010

Clearwater, Florida, United States, 33765

Finlay Medical Research-Site Number:8400014

Greenacres City, Florida, United States, 33467

Project 4 research, Inc.-Site Number:8400023

Miami, Florida, United States, 33125

Finlay Medical Research-Site Number:8400062

Miami, Florida, United States, 33126

Renstar Medical Research-Site Number:8400051

Ocala, Florida, United States, 34470

Florida Institute for Clinical Research, LLC-Site Number:8400029

Orlando, Florida, United States, 32825

Emerald Coast Research Associates-Site Number:8400032

Panama City, Florida, United States, 32405

Sarasota Clinical Research-Site Number:8400026

Sarasota, Florida, United States, 34239

United States, Georgia

VitaLink research-Hamilton Mill-Site Number:8400055

Dacula, Georgia, United States, 30019

DC Research Works-Site Number:8400016

Marietta, Georgia, United States, 30060

North Georgia Clinical Research-Site Number:8400025

Woodstock, Georgia, United States, 30189

United States, Maryland

Johns Hopkins University (Asthma and Allergy Center)-Site Number:8400012

Baltimore, Maryland, United States, 21224

Asthma Allergy & Sinus Center-Site Number:8400038

White Marsh, Maryland, United States, 21162

United States, Michigan

Michigan Medicine (University of Michigan)-Site Number:8400050

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

Mayo Clinic Lanmark Center 2-46-Site Number:8400065

Rochester, Minnesota, United States, 55905

United States, Missouri

Midwest Chest Consultants, P.C.-Site Number:8400011

Saint Charles, Missouri, United States, 63301

Washington University School of Medicine-Site Number:8400004

Saint Louis, Missouri, United States, 63104

United States, Nevada

Sierra Clinical Research-Site Number:8400035

Las Vegas, Nevada, United States, 89106

United States, New York

Va Western New York Healthcare-Site Number:8400067

Buffalo, New York, United States, 14215

IMA Clinical Research, LLC-Site Number:8400070

New York, New York, United States, 10036

United States, North Carolina

The University of North Carolina at Chapel Hill - Division of Pulmonary and Critical Care Medicine-Site Number:8400019

Chapel Hill, North Carolina, United States, 27514

American Health Research-Site Number:8400061

Charlotte, North Carolina, United States, 28277

Duke Asthma, Allergy and Airway Center-Site Number:8400064

Durham, North Carolina, United States, 27705

Accellacare-Site Number:8400052

Wilmington, North Carolina, United States, 28401

Southeastern Research Center-Site Number:8400060

Winston-Salem, North Carolina, United States, 27103-4027

United States, Ohio

Midwest Pulmonary and Sleep Research Center-Site Number:8400040

Dayton, Ohio, United States, 45459

Aventiv Research, Inc-Site Number:8400024

Dublin, Ohio, United States, 43016

United States, Oklahoma

OK Clinical Research-Site Number:8400005

Edmond, Oklahoma, United States, 73034

United States, Oregon

Velocity Clinical Research, Medford-Site Number:8400001

Medford, Oregon, United States, 97504

United States, Pennsylvania

Jefferson Associates in Internal Medicine-Site Number:8400037

Clairton, Pennsylvania, United States, 15025

Temple University Hospital-Site Number:8400009

Philadelphia, Pennsylvania, United States, 19140

Emphysema COPD Research Center, Kaufmann Medical Building-Site Number:8400033

Pittsburgh, Pennsylvania, United States, 15213

Berks Schuylkill Respiratory Specialists, LTD-Site Number:8400063

Wyomissing, Pennsylvania, United States, 19610

United States, South Carolina

VitaLink Research-Easley-Site Number:8400022

Easley, South Carolina, United States, 29640

VitaLink Research- Gaffney-Site Number:8400047

Gaffney, South Carolina, United States, 29340

VitaLink Research-Greenville-Site Number:8400007

Greenville, South Carolina, United States, 29615

Clinical Research of Charleston-Site Number:8400044

Mount Pleasant, South Carolina, United States, 29464

Clinical Research of Rock Hill-Site Number:8400046

Rock Hill, South Carolina, United States, 29732

VitaLink Research - Spartanburg-Site Number:8400048

Spartanburg, South Carolina, United States, 29303

United States, Tennessee

Clinical Trials Center of Middle Tennessee-Site Number:8400073

Franklin, Tennessee, United States, 37067

United States, Texas

Bayer College of Medicine-Site Number:8400018

Houston, Texas, United States, 77030

Metroplex Pulmonary and Sleep Center-Site Number:8400021

McKinney, Texas, United States, 75069

Sherman Clinical Research-Site Number:8400027

Sherman, Texas, United States, 75092

United States, Washington

MultiCare Institute for Research and Innovation-Site Number:8400036

Tacoma, Washington, United States, 98405

United States, Wisconsin

Allergy, Asthma & Sinus Center, S.C.-Site Number:8400008

Greenfield, Wisconsin, United States, 53228

Argentina

Investigational Site Number :0320011

Caba, Buenos Aires, Argentina, 1430

Investigational Site Number :0320002

Caba, Buenos Aires, Argentina, C1414AIF

Investigational Site Number :0320003

Caba, Buenos Aires, Argentina, C1425BEN

Investigational Site Number :0320004

Caba, Buenos Aires, Argentina, C1425FVH

Investigational Site Number :0320012

La Plata, Buenos Aires, Argentina, B1900BNN

Investigational Site Number :0320007

Quilmes, Ciudad De Buenos Aires, Argentina, B1878FNR

Investigational Site Number :0320006

Rosario, Santa Fe, Argentina, S2000DBS

Investigational Site Number :0320009

San Miguel de Tucumán, Tucumán, Argentina, T4000IAR

Investigational Site Number :0320001

Buenos Aires, Argentina, C1121ABE

Investigational Site Number :0320005

Buenos Aires, Argentina

Investigational Site Number :0320008

Mar Del Plata, Argentina, B7600

Investigational Site Number :0320010

Mendoza, Argentina, 5500

Bulgaria

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Haskovo, Bulgaria, 6305

Investigational Site Number :1001003

Montana, Bulgaria, 3400

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Ruse, Bulgaria, 7002

Investigational Site Number :1001009

Sofia, Bulgaria, 1202

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Sofia, Bulgaria, 1233

Investigational Site Number :1001001

Sofia, Bulgaria, 1680

Investigational Site Number :1001005

Stara Zagora, Bulgaria, 6001

Investigational Site Number :1001010

Troyan, Bulgaria, 5600

Canada, Alberta

Investigational Site Number :1240021

Edmonton, Alberta, Canada, T5H4B9

Investigational Site Number :1240015

Edmonton, Alberta, Canada, T6G 2G3

Investigational Site Number :1240016

Sherwood Park, Alberta, Canada, T8H 0N2

Canada, British Columbia

Investigational Site Number :1240017

Vancouver, British Columbia, Canada, V5Z 1M9

Investigational Site Number :1240007

Vancouver, British Columbia, Canada, V6Z 1Y6

Canada, Ontario

Investigational Site Number :1240002

Burlington, Ontario, Canada, L7N 3V2

Investigational Site Number :1240012

Toronto, Ontario, Canada, M5T 3A9

Investigational Site Number :1240013

Windsor, Ontario, Canada, N8X 5A6

Canada, Quebec

Investigational Site Number :1240009

Montreal, Quebec, Canada, H1M 1B1

Investigational Site Number :1240003

Montreal, Quebec, Canada, H1T 1C8

Investigational Site Number :1240001

Montreal, Quebec, Canada, H4A 3J1

Investigational Site Number :1240010

Sherbrooke, Quebec, Canada, J1H 5N4

Investigational Site Number :1240011

Sherbrooke, Quebec, Canada, J1L 0H8

Investigational Site Number :1240006

St-charles Borrommee, Quebec, Canada, J6E 2B4

Investigational Site Number :1240008

Trois-Rivieres, Quebec, Canada, G8T 7A1

Investigational Site Number :1240020

Victoriaville, Quebec, Canada, G6P 6P6

Canada

Investigational Site Number :1240005

Quebec, Canada, G1V 4G5

Investigational Site Number :1240004

Quebec, Canada, G1V 4W2

Investigational Site Number :1240019

Quebec, Canada, G3K 2P8

Investigational Site Number :1240018

Quebec, Canada, GIS 2L6

Chile

Investigational Site Number :1520006

Curicó, Maule, Chile, 3341643

Investigational Site Number :1520001

Talca, Maule, Chile

Investigational Site Number :1520009

Santiago, Reg Metropolitana De Santiago, Chile, 7500587

Investigational Site Number :1520003

Santiago, Reg Metropolitana De Santiago, Chile, 7500692

Investigational Site Number :1520005

Santiago, Reg Metropolitana De Santiago, Chile, 7500698

Investigational Site Number :1520008

Santiago, Reg Metropolitana De Santiago, Chile, 8380453

Investigational Site Number :1520002

Santiago, Reg Metropolitana De Santiago, Chile, 8910131

Investigational Site Number :1520004

Quillota, Valparaíso, Chile, 2260877

China

Investigational Site Number :1560037

Baotou, China, 014010

Investigational Site Number :1560006

Beijing, China

Investigational Site Number :1560003

Changchun, China, 130021

Investigational Site Number :1560022

Changsha, China, 410011

Investigational Site Number :1560021

Changsha, China, 410013

Investigational Site Number :1560001

Chengdu, China, 610041

Investigational Site Number :1560017

Chengdu, China, 611130

Investigational Site Number :1560012

Chongqing, China, 400037

Investigational Site Number :1560005

Chongqing, China, 400038

Investigational Site Number :1560053

Fuzhou, China, 350001

Investigational Site Number :1560036

Guangzhou, China, 510150

Investigational Site Number :1560019

Guangzhou, China, 510163

Investigational Site Number :1560045

Haikou, China, 570216

Investigational Site Number :1560018

Haikou, China, 570311

Investigational Site Number :1560046

Hangzhou, China, 310009

Investigational Site Number :1560009

Hefei, China, 230022

Investigational Site Number :1560041

Hefei, China

Investigational Site Number :1560015

Hohhot, China, 010017

Investigational Site Number :1560008

Hohhot, China, 010050

Investigational Site Number :1560027

Nanchang, China, 330006

Investigational Site Number :1560034

Nanjing, China, 210009

Investigational Site Number :1560032

Shanghai, China, 200025

Investigational Site Number :1560013

Shanghai, China, 200080

Investigational Site Number :1560007

Shanghai, China, 200433

Investigational Site Number :1560014

Shenyang, China, 110001

Investigational Site Number :1560004

Shenyang, China, 110004

Investigational Site Number :1560051

Shenzhen, China, 518020

Investigational Site Number :1560016

Shijiazhuang, China, 050000

Investigational Site Number :1560024

Taiyuan, China, 030001

Investigational Site Number :1560010

Tianjin, China, 300052

Investigational Site Number :1560028

Urumchi, China, 830054

Investigational Site Number :1560052

Wuhan, China, 430014

Investigational Site Number :1560020

Xi'An, China, 710061

Investigational Site Number :1560054

Xuzhou, China, 221002

Investigational Site Number :1560011

Yangzhou, China, 225001

Investigational Site Number :1560031

Zhanjiang, China, 524001

Investigational Site Number :1560002

Zhengzhou, China, 450003

Czechia

Investigational Site Number :2030002

Jindrichuv Hradec III, Czechia, 37701

Investigational Site Number :2030005

Karlovy Vary, Czechia, 36017

Investigational Site Number :2030009

Miroslav, Czechia, 67172

Investigational Site Number :2030001

Novy Bor, Czechia, 47301

Investigational Site Number :2030003

Praha 4, Czechia, 14059

Investigational Site Number :2030008

Praha 6 - Brevnov, Czechia, 16900

Investigational Site Number :2030004

Rokycany, Czechia, 33722

Investigational Site Number :2030006

Strakonice, Czechia, 38601

Denmark

Investigational Site Number :2080001

Copenhagen Nv, Denmark, 2400

Investigational Site Number :2080002

Hvidovre, Denmark, 2650

Investigational Site Number :2080006

Naestved, Denmark, 4700

Investigational Site Number :2080005

Odense C, Denmark, 5000

Investigational Site Number :2080004

Roskilde, Denmark, 4000

Investigational Site Number :2080007

Vejle, Denmark, 7100

Investigational Site Number :2080003

Ålborg, Denmark, 9100

Finland

Investigational Site Number :2460003

Pori, Finland, 28500

Investigational Site Number :2460001

Turku, Finland, 20520

Germany

Investigational Site Number :2760006

Berlin, Germany, 10787

Investigational Site Number :2760009

Frankfurt am Main, Germany, 60596

Investigational Site Number :2760002

Hamburg, Germany, 20354

Investigational Site Number :2760007

Koblenz, Germany, 56068

Investigational Site Number :2760011

Leipzig, Germany, 04347

Investigational Site Number :2760010

Lübeck, Germany, 23552

Investigational Site Number :2760008

Marburg, Germany, 35043

Hungary

Investigational Site Number :3480007

Balassagyarmat, Hungary, 2660

Investigational Site Number :3480011

Budapest, Hungary, 1122

Investigational Site Number :3480008

Edelény, Hungary, 3780

Investigational Site Number :3480001

Gödöllö, Hungary, 2100

Investigational Site Number :3480010

Hajdunánás, Hungary, 4080

Investigational Site Number :3480002

Komarom, Hungary, 2900

Investigational Site Number :3480003

Makó, Hungary, 6900

Investigational Site Number :3480006

Mohács, Hungary, 7700

Investigational Site Number :3480012

Puspokladany, Hungary, 4150

Investigational Site Number :3480005

Szombathely, Hungary, 9700

Investigational Site Number :3480004

Százhalombatta, Hungary, 2440

Israel

Investigational Site Number :3760006

Ashkelon, Israel, 78278

Investigational Site Number :3760007

Beer Sheva, Israel, 84101

Investigational Site Number :3760003

Haifa, Israel, 34362

Investigational Site Number :3760005

Jerusalem, Israel, 91031

Investigational Site Number :3760004

Jerusalem, Israel, 91120

Investigational Site Number :3760001

Petah-Tikva, Israel, 49100

Investigational Site Number :3760002

Rehovot, Israel, 76100

Italy

Investigational Site Number :3800004

Cona, Ferrara, Italy, 44124

Investigational Site Number :3800003

Rozzano, Milano, Italy, 20089

Investigational Site Number :3800007

Pisa, Italy, 56124

Investigational Site Number :3800001

Reggio Emilia, Italy, 42123

Investigational Site Number :3800005

Roma, Italy, 00133

Japan

Investigational Site Number :3920013

Kasuga-shi, Fukuoka, Japan, 816-0813

Investigational Site Number :3920011

Himeji-shi, Hyogo, Japan, 670-0849

Investigational Site Number :3920023

Higashiibaraki-gun, Ibaraki, Japan, 311-3193

Investigational Site Number :3920014

Naka-gun, Ibaraki, Japan, 319-1113

Investigational Site Number :3920019

Takamatsu-shi, Kagawa, Japan, 761-8073

Investigational Site Number :3920027

Yokohama-shi, Kanagawa, Japan, 223-0059

Investigational Site Number :3920003

Joyo-shi, Kyoto, Japan, 610-0113

Investigational Site Number :3920017

Kyoto-shi, Kyoto, Japan, 612-8555

Investigational Site Number :3920006

Ueda-shi, Nagano, Japan

Investigational Site Number :3920029

Urasoe-shi, Okinawa, Japan, 901-2121

Investigational Site Number :3920018

Kawachinagano-shi, Osaka, Japan, 586-8521

Investigational Site Number :3920001

Kishiwada-shi, Osaka, Japan, 596-8501

Investigational Site Number :3920028

Osaka-shi, Osaka, Japan, 531-0073

Investigational Site Number :3920012

Sakai-shi, Osaka, Japan, 591-8555

Investigational Site Number :3920021

Hamamatsu-shi, Shizuoka, Japan, 434-8511

Investigational Site Number :3920008

Chuo-ku, Tokyo, Japan, 103-0022

Investigational Site Number :3920030

Chuo-ku, Tokyo, Japan, 103-0028

Investigational Site Number :3920005

Chuo-ku, Tokyo, Japan, 104-0031

Investigational Site Number :3920015

Kokubunji-shi, Tokyo, Japan, 185-0014

Investigational Site Number :3920016

Shinagawa-ku, Tokyo, Japan, 140-8522

Investigational Site Number :3920004

Toshima-ku, Tokyo, Japan, 170-0003

Investigational Site Number :3920026

Toshima-ku, Tokyo, Japan, 1710014

Korea, Republic of

Investigational Site Number :4100003

Wonju, Gangwon-do, Korea, Republic of, 26426

Investigational Site Number :4100004

Seongnam, Gyeonggi-do, Korea, Republic of, 13620

Investigational Site Number :4100008

Incheon, Incheon-gwangyeoksi, Korea, Republic of, 21431

Investigational Site Number :4100001

Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03080

Investigational Site Number :4100009

Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03312

Investigational Site Number :4100007

Seoul, Seoul-teukbyeolsi, Korea, Republic of, 05505

Mexico

Investigational Site Number :4840002

Guadalajara, Jalisco, Mexico, 44100

Investigational Site Number :4840001

Monterrey, Nuevo León, Mexico, 64460

Investigational Site Number :4840004

Chihuahua, Mexico, 31000

Investigational Site Number :4840003

Durango, Mexico, 34080

Investigational Site Number :4840006

Mexico Distrito Federal, Mexico, 06700

Investigational Site Number :4840007

Oaxaca, Mexico, 68000

Investigational Site Number :4840005

Veracruz, Mexico, 91910

Poland

Investigational Site Number :6160009

Grudziadz, Kujawsko-pomorskie, Poland, 86-300

Investigational Site Number :6160007

Krakow, Malopolskie, Poland, 31-559

Investigational Site Number :6160015

Grodzisk Mazowiecki, Mazowieckie, Poland, 05-825

Investigational Site Number :6160012

Warszawa, Mazowieckie, Poland, 01-456

Investigational Site Number :6160008

Bialystok, Podlaskie, Poland, 15-044

Investigational Site Number :6160014

Elblag, Pomorskie, Poland, 82-300

Investigational Site Number :6160011

Katowice, Slaskie, Poland, 40-648

Investigational Site Number :6160016

Poznan, Wielkopolskie, Poland, 60-214

Investigational Site Number :6160006

Poznan, Wielkopolskie, Poland, 61-578

Romania

Investigational Site Number :6420001

Bucharest, Romania, 011461

Investigational Site Number :6420009

Bucuresti, Romania, 030303

Investigational Site Number :6420008

Bucuresti, Romania, 050159

Investigational Site Number :6420003

Cluj-Napoca, Romania, 400371

Investigational Site Number :6420004

Cluj-Napoca, Romania, 400371

Investigational Site Number :6420007

Constanta, Romania, 900002

Investigational Site Number :6420006

Timisoara, Romania, 300310

Investigational Site Number :6420010

Timisoara, Romania, 300310

Russian Federation

Investigational Site Number :6430003

Chelyabinsk, Russian Federation, 454091

Investigational Site Number :6430004

Kazan, Russian Federation, 420008

Investigational Site Number :6430006

Moscow, Russian Federation, 105077

Investigational Site Number :6430001

Moscow, Russian Federation, 115093

Investigational Site Number :6430005

Moscow, Russian Federation, 115280

Investigational Site Number :6430008

Moscow, Russian Federation, 115682

Investigational Site Number :6430002

Moscow, Russian Federation, 117546

Investigational Site Number :6430009

Moscow, Russian Federation, 125284

Investigational Site Number :6430007

St-Petersburg, Russian Federation, 193231

Slovakia

Investigational Site Number :7030007

Banska Bystrica, Slovakia, 97517

Investigational Site Number :7030006

Humenne, Slovakia, 066 01

Investigational Site Number :7030003

Levice, Slovakia, 93401

Investigational Site Number :7030001

Poprad, Slovakia, 058 01

Investigational Site Number :7030002

Spisska Nova Ves, Slovakia, 05201

Spain

Investigational Site Number :7240096

Santiago de Compostela, A Coruña [La Coruña], Spain, 15706

Investigational Site Number :7240002

Barcelona, Barcelona [Barcelona], Spain, 08035

Investigational Site Number :7240007

Sant Boi de Llobregat, Barcelona [Barcelona], Spain, 08830

Investigational Site Number :7240005

Mérida / Badajoz, Extremadura, Spain, 06800

Investigational Site Number :7240006

Pozuelo de Alarcón, Madrid, Spain, 28223

Investigational Site Number :7240003

Madrid, Spain, 28007

Investigational Site Number :7240001

Málaga, Spain, 29010

Investigational Site Number :7240010

Palma de Mallorca, Spain, 07120

Investigational Site Number :7240004

Valencia, Spain, 46015

Sweden

Investigational Site Number :7520001

Lund, Sweden, 221 85

Investigational Site Number :7520002

Stockholm, Sweden, 114 46

Turkey

Investigational Site Number :7920004

Ankara, Turkey, 06100

Investigational Site Number :7920001

Istanbul, Turkey, 34098

Investigational Site Number :7920006

Izmir, Turkey, 35040

Investigational Site Number :7920007

Izmir, Turkey, 35110

Investigational Site Number :7920008

Kirikkale, Turkey, 71450

Investigational Site Number :7920005

Manisa, Turkey, 45000

Investigational Site Number :7920002

Mersin, Turkey, 33070

Ukraine

Investigational Site Number :8040003

Chernivtsi, Ukraine, 58001

Investigational Site Number :8040001

Ivano-Frankivsk, Ukraine, 76018

Investigational Site Number :8040006

Kharkiv, Ukraine, 61166

Investigational Site Number :8040004

Kyiv, Ukraine, 02125

Investigational Site Number :8040009

Odesa, Ukraine, 65025

Investigational Site Number :8040002

Ternopil, Ukraine, 46000

Investigational Site Number :8040005

Vinnytsya, Ukraine, 21001

Investigational Site Number :8040007

Zhytomyr, Ukraine, 10002

Sponsors and Collaborators

Sanofi

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

  Study Documents (Full-Text)

Documents provided by Sanofi:

Study Protocol  [PDF] November 7, 2018

Statistical Analysis Plan  [PDF] March 23, 2020

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT03930732
• Other Study ID Numbers: EFC15804; 2018-001953-28 ( EudraCT Number ); U1111-1211-8804 ( Other Identifier: UTN )
• First Posted: April 29, 2019
• Results First Posted: February 28, 2024
• Last Update Posted: February 28, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Inflammation; Pathologic Processes; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Cholinergic Agents; Muscarinic Antagonists; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Cholinergic Antagonists