Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate-to-severe COPD With Type 2 Inflammation
- Conditions
- Chronic Obstructive Pulmonary Disease
- Interventions
- Drug: Inhaled CorticosteroidDrug: Inhaled Long-Acting Beta AgonistDrug: PlaceboDrug: Inhaled Long-Acting Muscarinic Antagonist
- Registration Number
- NCT03930732
- Lead Sponsor
- Sanofi
- 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)
- Detailed Description
Approximately 68 weeks including a 4-week screening period, a 52-week treatment period, and 12 weeks of follow-up.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 939
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dupilumab Inhaled Corticosteroid 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). Dupilumab Dupilumab SAR231893 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). Dupilumab Inhaled Long-Acting Beta Agonist 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). Placebo Inhaled Long-Acting Beta Agonist 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). Placebo 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). Dupilumab Inhaled Long-Acting Muscarinic Antagonist 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). Placebo Inhaled Long-Acting Muscarinic Antagonist 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). Placebo Inhaled Corticosteroid 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).
- Primary Outcome Measures
Name Time Method Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-Week Treatment Period 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
Name Time Method Change From Baseline in Pre-BD FEV1 at Week 52 in Subgroup of Participants With Baseline FeNO >=20 Ppb 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.
Change From Baseline in Pre-BD FEV1 at Week 52 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.
Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) at Week 12 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.
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) 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.
Annualized Rate of Severe COPD Exacerbations Over the 52-Week Treatment Period 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.
Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab 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.
Change From Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 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.
Percentage of Participants With SGRQ Improvement >=4 Points at Week 52 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.
Change From Baseline in Evaluating Respiratory Symptoms (E-RS) in COPD (E-RS: COPD) RS-Total Score at Week 52 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.
Annualized Rate of Moderate or Severe COPD Exacerbation Over the 52-Week Treatment Period in Subgroup of Participants With Baseline FeNO >=20 Ppb 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.
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 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.
Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44 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.
Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) 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.
Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52 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.
Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period 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.
Trial Locations
- Locations (275)
Investigational Site Number :1240013
🇨🇦Windsor, Ontario, Canada
Investigational Site Number :1240021
🇨🇦Edmonton, Alberta, Canada
Investigational Site Number :1560037
🇨🇳Baotou, China
Investigational Site Number :1560052
🇨🇳Wuhan, China
Investigational Site Number :1560054
🇨🇳Xuzhou, China
Investigational Site Number :7520001
🇸🇪Lund, Sweden
Project 4 research, Inc.-Site Number:8400023
🇺🇸Miami, Florida, United States
DC Research Works-Site Number:8400016
🇺🇸Marietta, Georgia, United States
SEC Clinical Research, LLC-Site Number:8400059
🇺🇸Dothan, Alabama, United States
Pulmonary Associates of Mobile, P.C.-Site Number:8400057
🇺🇸Mobile, Alabama, United States
Clinical Research Of West Florida Inc-Site Number:8400010
🇺🇸Clearwater, Florida, United States
Johns Hopkins University (Asthma and Allergy Center)-Site Number:8400012
🇺🇸Baltimore, Maryland, United States
Aventiv Research, Inc-Site Number:8400024
🇺🇸Dublin, Ohio, United States
Finlay Medical Research-Site Number:8400062
🇺🇸Miami, Florida, United States
Sarasota Clinical Research-Site Number:8400026
🇺🇸Sarasota, Florida, United States
Velocity Clinical Research, Medford-Site Number:8400001
🇺🇸Medford, Oregon, United States
Temple University Hospital-Site Number:8400009
🇺🇸Philadelphia, Pennsylvania, United States
Emphysema COPD Research Center, Kaufmann Medical Building-Site Number:8400033
🇺🇸Pittsburgh, Pennsylvania, United States
Bayer College of Medicine-Site Number:8400018
🇺🇸Houston, Texas, United States
Investigational Site Number :1240012
🇨🇦Toronto, Ontario, Canada
Investigational Site Number :1240010
🇨🇦Sherbrooke, Quebec, Canada
Investigational Site Number :1240011
🇨🇦Sherbrooke, Quebec, Canada
Investigational Site Number :4840001
🇲🇽Monterrey, Nuevo León, Mexico
Duke Asthma, Allergy and Airway Center-Site Number:8400064
🇺🇸Durham, North Carolina, United States
Investigational Site Number :2080003
🇩🇰Ålborg, Denmark
Investigational Site Number :1560006
🇨🇳Beijing, China
Investigational Site Number :1560005
🇨🇳Chongqing, China
Investigational Site Number :1560024
🇨🇳Taiyuan, China
Investigational Site Number :1560002
🇨🇳Zhengzhou, China
Investigational Site Number :1520006
🇨🇱Curicó, Maule, Chile
Investigational Site Number :2080002
🇩🇰Hvidovre, Denmark
Investigational Site Number :1520009
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1240016
🇨🇦Sherwood Park, Alberta, Canada
Sierra Clinical Research-Site Number:8400035
🇺🇸Las Vegas, Nevada, United States
Investigational Site Number :0320004
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number :0320005
🇦🇷Buenos Aires, Argentina
Investigational Site Number :1001005
🇧🇬Stara Zagora, Bulgaria
Investigational Site Number :1001010
🇧🇬Troyan, Bulgaria
Investigational Site Number :3480008
🇭🇺Edelény, Hungary
Investigational Site Number :0320007
🇦🇷Quilmes, Ciudad De Buenos Aires, Argentina
Investigational Site Number :0320010
🇦🇷Mendoza, Argentina
Investigational Site Number :1001006
🇧🇬Ruse, Bulgaria
VitaLink Research-Easley-Site Number:8400022
🇺🇸Easley, South Carolina, United States
Investigational Site Number :2460001
🇫🇮Turku, Finland
Investigational Site Number :3480004
🇭🇺Százhalombatta, Hungary
Investigational Site Number :1240017
🇨🇦Vancouver, British Columbia, Canada
VitaLink Research- Gaffney-Site Number:8400047
🇺🇸Gaffney, South Carolina, United States
Investigational Site Number :0320009
🇦🇷San Miguel de Tucumán, Tucumán, Argentina
Investigational Site Number :0320012
🇦🇷La Plata, Buenos Aires, Argentina
VitaLink Research - Spartanburg-Site Number:8400048
🇺🇸Spartanburg, South Carolina, United States
Investigational Site Number :1520002
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1240007
🇨🇦Vancouver, British Columbia, Canada
VitaLink Research-Greenville-Site Number:8400007
🇺🇸Greenville, South Carolina, United States
Clinical Research of Charleston-Site Number:8400044
🇺🇸Mount Pleasant, South Carolina, United States
Investigational Site Number :0320003
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number :0320001
🇦🇷Buenos Aires, Argentina
Investigational Site Number :1001004
🇧🇬Haskovo, Bulgaria
Investigational Site Number :1001001
🇧🇬Sofia, Bulgaria
Investigational Site Number :1240008
🇨🇦Trois-Rivieres, Quebec, Canada
Investigational Site Number :1520004
🇨🇱Quillota, Valparaíso, Chile
Investigational Site Number :1520005
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1520008
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :3480003
🇭🇺Makó, Hungary
Investigational Site Number :3760003
🇮🇱Haifa, Israel
Investigational Site Number :3760005
🇮🇱Jerusalem, Israel
Investigational Site Number :3800004
🇮🇹Cona, Ferrara, Italy
Investigational Site Number :3920027
🇯🇵Yokohama-shi, Kanagawa, Japan
Investigational Site Number :6420009
🇷🇴Bucuresti, Romania
Investigational Site Number :6420004
🇷🇴Cluj-Napoca, Romania
Investigational Site Number :6420007
🇷🇴Constanta, Romania
Investigational Site Number :3480006
🇭🇺Mohács, Hungary
Investigational Site Number :3480012
🇭🇺Puspokladany, Hungary
Investigational Site Number :4840004
🇲🇽Chihuahua, Mexico
Investigational Site Number :6160009
🇵🇱Grudziadz, Kujawsko-pomorskie, Poland
Investigational Site Number :7030003
🇸🇰Levice, Slovakia
Investigational Site Number :8040003
🇺🇦Chernivtsi, Ukraine
Investigational Site Number :3480005
🇭🇺Szombathely, Hungary
Investigational Site Number :3760004
🇮🇱Jerusalem, Israel
Investigational Site Number :3760001
🇮🇱Petah-Tikva, Israel
Investigational Site Number :3920006
🇯🇵Ueda-shi, Nagano, Japan
Investigational Site Number :3920019
🇯🇵Takamatsu-shi, Kagawa, Japan
Investigational Site Number :3920001
🇯🇵Kishiwada-shi, Osaka, Japan
Investigational Site Number :4840003
🇲🇽Durango, Mexico
Investigational Site Number :4840006
🇲🇽Mexico Distrito Federal, Mexico
Investigational Site Number :4840007
🇲🇽Oaxaca, Mexico
Investigational Site Number :6160012
🇵🇱Warszawa, Mazowieckie, Poland
Investigational Site Number :6160008
🇵🇱Bialystok, Podlaskie, Poland
Investigational Site Number :6160014
🇵🇱Elblag, Pomorskie, Poland
Investigational Site Number :6160006
🇵🇱Poznan, Wielkopolskie, Poland
Investigational Site Number :6420003
🇷🇴Cluj-Napoca, Romania
Investigational Site Number :6430004
🇷🇺Kazan, Russian Federation
Investigational Site Number :8040006
🇺🇦Kharkiv, Ukraine
Investigational Site Number :6430002
🇷🇺Moscow, Russian Federation
Investigational Site Number :3920030
🇯🇵Chuo-ku, Tokyo, Japan
Investigational Site Number :6160011
🇵🇱Katowice, Slaskie, Poland
Investigational Site Number :6160016
🇵🇱Poznan, Wielkopolskie, Poland
Investigational Site Number :6420006
🇷🇴Timisoara, Romania
Investigational Site Number :6430001
🇷🇺Moscow, Russian Federation
Investigational Site Number :6430005
🇷🇺Moscow, Russian Federation
Investigational Site Number :6430009
🇷🇺Moscow, Russian Federation
Investigational Site Number :6430003
🇷🇺Chelyabinsk, Russian Federation
Investigational Site Number :6430007
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number :8040002
🇺🇦Ternopil, Ukraine
Investigational Site Number :7030006
🇸🇰Humenne, Slovakia
Investigational Site Number :7030001
🇸🇰Poprad, Slovakia
Investigational Site Number :8040009
🇺🇦Odesa, Ukraine
Investigational Site Number :8040005
🇺🇦Vinnytsya, Ukraine
Investigational Site Number :8040007
🇺🇦Zhytomyr, Ukraine
Clinical Research Center of Alabama, LLC-Site Number:8400041
🇺🇸Birmingham, Alabama, United States
UAB Lung Health Center-Site Number:8400013
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Lanmark Center 2-46-Site Number:8400065
🇺🇸Rochester, Minnesota, United States
Investigational Site Number :6430008
🇷🇺Moscow, Russian Federation
SEC Clinical Research, LLC-Site Number:8400030
🇺🇸Andalusia, Alabama, United States
Finlay Medical Research-Site Number:8400014
🇺🇸Greenacres City, Florida, United States
Renstar Medical Research-Site Number:8400051
🇺🇸Ocala, Florida, United States
VitaLink research-Hamilton Mill-Site Number:8400055
🇺🇸Dacula, Georgia, United States
Emerald Coast Research Associates-Site Number:8400032
🇺🇸Panama City, Florida, United States
North Georgia Clinical Research-Site Number:8400025
🇺🇸Woodstock, Georgia, United States
Asthma Allergy & Sinus Center-Site Number:8400038
🇺🇸White Marsh, Maryland, United States
Midwest Chest Consultants, P.C.-Site Number:8400011
🇺🇸Saint Charles, Missouri, United States
Va Western New York Healthcare-Site Number:8400067
🇺🇸Buffalo, New York, United States
Washington University School of Medicine-Site Number:8400004
🇺🇸Saint Louis, Missouri, United States
American Health Research-Site Number:8400061
🇺🇸Charlotte, North Carolina, United States
IMA Clinical Research, LLC-Site Number:8400070
🇺🇸New York, New York, United States
Midwest Pulmonary and Sleep Research Center-Site Number:8400040
🇺🇸Dayton, Ohio, United States
Accellacare-Site Number:8400052
🇺🇸Wilmington, North Carolina, United States
Jefferson Associates in Internal Medicine-Site Number:8400037
🇺🇸Clairton, Pennsylvania, United States
OK Clinical Research-Site Number:8400005
🇺🇸Edmond, Oklahoma, United States
Berks Schuylkill Respiratory Specialists, LTD-Site Number:8400063
🇺🇸Wyomissing, Pennsylvania, United States
Clinical Trials Center of Middle Tennessee-Site Number:8400073
🇺🇸Franklin, Tennessee, United States
Metroplex Pulmonary and Sleep Center-Site Number:8400021
🇺🇸McKinney, Texas, United States
MultiCare Institute for Research and Innovation-Site Number:8400036
🇺🇸Tacoma, Washington, United States
Sherman Clinical Research-Site Number:8400027
🇺🇸Sherman, Texas, United States
Allergy, Asthma & Sinus Center, S.C.-Site Number:8400008
🇺🇸Greenfield, Wisconsin, United States
Investigational Site Number :0320011
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number :0320002
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number :0320006
🇦🇷Rosario, Santa Fe, Argentina
Investigational Site Number :0320008
🇦🇷Mar Del Plata, Argentina
Investigational Site Number :1001003
🇧🇬Montana, Bulgaria
Investigational Site Number :1001009
🇧🇬Sofia, Bulgaria
Investigational Site Number :1001002
🇧🇬Sofia, Bulgaria
Investigational Site Number :1240015
🇨🇦Edmonton, Alberta, Canada
Investigational Site Number :1240009
🇨🇦Montreal, Quebec, Canada
Investigational Site Number :1240002
🇨🇦Burlington, Ontario, Canada
Investigational Site Number :1240003
🇨🇦Montreal, Quebec, Canada
Investigational Site Number :1240001
🇨🇦Montreal, Quebec, Canada
Investigational Site Number :1240006
🇨🇦St-charles Borrommee, Quebec, Canada
Investigational Site Number :1240020
🇨🇦Victoriaville, Quebec, Canada
Investigational Site Number :1240005
🇨🇦Quebec, Canada
Investigational Site Number :1240004
🇨🇦Quebec, Canada
Investigational Site Number :1240019
🇨🇦Quebec, Canada
Investigational Site Number :1240018
🇨🇦Quebec, Canada
Investigational Site Number :1520001
🇨🇱Talca, Maule, Chile
Investigational Site Number :1520003
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1560003
🇨🇳Changchun, China
Investigational Site Number :1560021
🇨🇳Changsha, China
Investigational Site Number :1560022
🇨🇳Changsha, China
Investigational Site Number :1560017
🇨🇳Chengdu, China
Investigational Site Number :1560001
🇨🇳Chengdu, China
Investigational Site Number :1560036
🇨🇳Guangzhou, China
Investigational Site Number :1560012
🇨🇳Chongqing, China
Investigational Site Number :1560053
🇨🇳Fuzhou, China
Investigational Site Number :1560019
🇨🇳Guangzhou, China
Investigational Site Number :1560045
🇨🇳Haikou, China
Investigational Site Number :1560018
🇨🇳Haikou, China
Investigational Site Number :1560046
🇨🇳Hangzhou, China
Investigational Site Number :1560016
🇨🇳Shijiazhuang, China
Investigational Site Number :1560009
🇨🇳Hefei, China
Investigational Site Number :1560015
🇨🇳Hohhot, China
Investigational Site Number :1560027
🇨🇳Nanchang, China
Investigational Site Number :1560041
🇨🇳Hefei, China
Investigational Site Number :1560008
🇨🇳Hohhot, China
Investigational Site Number :1560032
🇨🇳Shanghai, China
Investigational Site Number :1560034
🇨🇳Nanjing, China
Investigational Site Number :1560013
🇨🇳Shanghai, China
Investigational Site Number :1560007
🇨🇳Shanghai, China
Investigational Site Number :1560014
🇨🇳Shenyang, China
Investigational Site Number :1560051
🇨🇳Shenzhen, China
Investigational Site Number :1560004
🇨🇳Shenyang, China
Investigational Site Number :1560010
🇨🇳Tianjin, China
Investigational Site Number :1560028
🇨🇳Urumchi, China
Investigational Site Number :1560031
🇨🇳Zhanjiang, China
Investigational Site Number :1560020
🇨🇳Xi'An, China
Investigational Site Number :1560011
🇨🇳Yangzhou, China
Investigational Site Number :2030002
🇨🇿Jindrichuv Hradec III, Czechia
Investigational Site Number :2030005
🇨🇿Karlovy Vary, Czechia
Investigational Site Number :2030001
🇨🇿Novy Bor, Czechia
Investigational Site Number :2030009
🇨🇿Miroslav, Czechia
Investigational Site Number :2030003
🇨🇿Praha 4, Czechia
Investigational Site Number :2030004
🇨🇿Rokycany, Czechia
Investigational Site Number :3760006
🇮🇱Ashkelon, Israel
Investigational Site Number :2030008
🇨🇿Praha 6 - Brevnov, Czechia
Investigational Site Number :2030006
🇨🇿Strakonice, Czechia
Investigational Site Number :2080001
🇩🇰Copenhagen Nv, Denmark
Investigational Site Number :2080006
🇩🇰Naestved, Denmark
Investigational Site Number :2460003
🇫🇮Pori, Finland
Investigational Site Number :2080007
🇩🇰Vejle, Denmark
Investigational Site Number :2080005
🇩🇰Odense C, Denmark
Investigational Site Number :2080004
🇩🇰Roskilde, Denmark
Investigational Site Number :2760002
🇩🇪Hamburg, Germany
Investigational Site Number :2760006
🇩🇪Berlin, Germany
Investigational Site Number :2760009
🇩🇪Frankfurt am Main, Germany
Investigational Site Number :2760010
🇩🇪Lübeck, Germany
Investigational Site Number :2760011
🇩🇪Leipzig, Germany
Investigational Site Number :2760008
🇩🇪Marburg, Germany
Investigational Site Number :2760007
🇩🇪Koblenz, Germany
Investigational Site Number :3480007
🇭🇺Balassagyarmat, Hungary
Investigational Site Number :3480011
🇭🇺Budapest, Hungary
Investigational Site Number :3480001
🇭🇺Gödöllö, Hungary
Investigational Site Number :3480010
🇭🇺Hajdunánás, Hungary
Investigational Site Number :3480002
🇭🇺Komarom, Hungary
Investigational Site Number :3760007
🇮🇱Beer Sheva, Israel
Investigational Site Number :3800003
🇮🇹Rozzano, Milano, Italy
Investigational Site Number :3760002
🇮🇱Rehovot, Israel
Investigational Site Number :3800007
🇮🇹Pisa, Italy
Investigational Site Number :3800005
🇮🇹Roma, Italy
Investigational Site Number :3800001
🇮🇹Reggio Emilia, Italy
Investigational Site Number :3920011
🇯🇵Himeji-shi, Hyogo, Japan
Investigational Site Number :3920013
🇯🇵Kasuga-shi, Fukuoka, Japan
Investigational Site Number :3920023
🇯🇵Higashiibaraki-gun, Ibaraki, Japan
Investigational Site Number :3920003
🇯🇵Joyo-shi, Kyoto, Japan
Investigational Site Number :3920014
🇯🇵Naka-gun, Ibaraki, Japan
Investigational Site Number :3920017
🇯🇵Kyoto-shi, Kyoto, Japan
Investigational Site Number :3920029
🇯🇵Urasoe-shi, Okinawa, Japan
Investigational Site Number :3920018
🇯🇵Kawachinagano-shi, Osaka, Japan
Investigational Site Number :3920028
🇯🇵Osaka-shi, Osaka, Japan
Investigational Site Number :3920012
🇯🇵Sakai-shi, Osaka, Japan
Investigational Site Number :3920021
🇯🇵Hamamatsu-shi, Shizuoka, Japan
Investigational Site Number :3920008
🇯🇵Chuo-ku, Tokyo, Japan
Investigational Site Number :3920005
🇯🇵Chuo-ku, Tokyo, Japan
Investigational Site Number :3920015
🇯🇵Kokubunji-shi, Tokyo, Japan
Investigational Site Number :3920004
🇯🇵Toshima-ku, Tokyo, Japan
Investigational Site Number :3920026
🇯🇵Toshima-ku, Tokyo, Japan
Investigational Site Number :3920016
🇯🇵Shinagawa-ku, Tokyo, Japan
Investigational Site Number :4100003
🇰🇷Wonju, Gangwon-do, Korea, Republic of
Investigational Site Number :4100008
🇰🇷Incheon, Incheon-gwangyeoksi, Korea, Republic of
Investigational Site Number :4100004
🇰🇷Seongnam, Gyeonggi-do, Korea, Republic of
Investigational Site Number :4100001
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4100009
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4100007
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4840002
🇲🇽Guadalajara, Jalisco, Mexico
Investigational Site Number :4840005
🇲🇽Veracruz, Mexico
Investigational Site Number :6160007
🇵🇱Krakow, Malopolskie, Poland
Investigational Site Number :6160015
🇵🇱Grodzisk Mazowiecki, Mazowieckie, Poland
Investigational Site Number :6420001
🇷🇴Bucharest, Romania
Investigational Site Number :6420008
🇷🇴Bucuresti, Romania
Investigational Site Number :6420010
🇷🇴Timisoara, Romania
Investigational Site Number :6430006
🇷🇺Moscow, Russian Federation
Investigational Site Number :7030007
🇸🇰Banska Bystrica, Slovakia
Investigational Site Number :7240002
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number :7030002
🇸🇰Spisska Nova Ves, Slovakia
Investigational Site Number :7240007
🇪🇸Sant Boi de Llobregat, Barcelona [Barcelona], Spain
Investigational Site Number :7240096
🇪🇸Santiago de Compostela, A Coruña [La Coruña], Spain
Investigational Site Number :7240005
🇪🇸Mérida / Badajoz, Extremadura, Spain
Investigational Site Number :7240006
🇪🇸Pozuelo de Alarcón, Madrid, Spain
Investigational Site Number :7240003
🇪🇸Madrid, Spain
Investigational Site Number :7240004
🇪🇸Valencia, Spain
Investigational Site Number :7240001
🇪🇸Málaga, Spain
Investigational Site Number :7240010
🇪🇸Palma de Mallorca, Spain
Investigational Site Number :7920004
🇹🇷Ankara, Turkey
Investigational Site Number :7920001
🇹🇷Istanbul, Turkey
Investigational Site Number :7920006
🇹🇷Izmir, Turkey
Investigational Site Number :7920008
🇹🇷Kirikkale, Turkey
Investigational Site Number :7520002
🇸🇪Stockholm, Sweden
Investigational Site Number :7920007
🇹🇷Izmir, Turkey
Investigational Site Number :7920005
🇹🇷Manisa, Turkey
Investigational Site Number :7920002
🇹🇷Mersin, Turkey
Investigational Site Number :8040001
🇺🇦Ivano-Frankivsk, Ukraine
Investigational Site Number :8040004
🇺🇦Kyiv, Ukraine
Asthma and Allergy Associates, PC-Site Number:8400034
🇺🇸Colorado Springs, Colorado, United States
The University of North Carolina at Chapel Hill - Division of Pulmonary and Critical Care Medicine-Site Number:8400019
🇺🇸Chapel Hill, North Carolina, United States
Michigan Medicine (University of Michigan)-Site Number:8400050
🇺🇸Ann Arbor, Michigan, United States
Florida Institute for Clinical Research, LLC-Site Number:8400029
🇺🇸Orlando, Florida, United States
Southeastern Research Center-Site Number:8400060
🇺🇸Winston-Salem, North Carolina, United States
Clinical Research of Rock Hill-Site Number:8400046
🇺🇸Rock Hill, South Carolina, United States