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

Chronic Obstructive Pulmonary Disease Clinical Trial

— BOREAS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03930732
• Other study ID #: EFC15804
• Secondary ID: 2018-001953-28U1
• Status: Completed
• Phase: Phase 3
• Start date: April 15, 2019
• Est. completion date: May 2, 2023

Study information

• Verified date: January 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 939
• Est. completion date: May 2, 2023
• Est. primary completion date: February 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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 a-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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Inflammation
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Dupilumab SAR231893
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
• Inhaled Corticosteroid
Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation
• Inhaled Long-Acting Beta Agonist
Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation
• Inhaled Long-Acting Muscarinic Antagonist
Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation
• Placebo
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Locations

Country	Name	City	State
Argentina	Investigational Site Number :0320001	Buenos Aires
Argentina	Investigational Site Number :0320005	Buenos Aires
Argentina	Investigational Site Number :0320002	Caba	Buenos Aires
Argentina	Investigational Site Number :0320003	Caba	Buenos Aires
Argentina	Investigational Site Number :0320004	Caba	Buenos Aires
Argentina	Investigational Site Number :0320011	Caba	Buenos Aires
Argentina	Investigational Site Number :0320012	La Plata	Buenos Aires
Argentina	Investigational Site Number :0320008	Mar Del Plata
Argentina	Investigational Site Number :0320010	Mendoza
Argentina	Investigational Site Number :0320007	Quilmes	Ciudad De Buenos Aires
Argentina	Investigational Site Number :0320006	Rosario	Santa Fe
Argentina	Investigational Site Number :0320009	San Miguel de Tucumán	Tucumán
Bulgaria	Investigational Site Number :1001004	Haskovo
Bulgaria	Investigational Site Number :1001003	Montana
Bulgaria	Investigational Site Number :1001006	Ruse
Bulgaria	Investigational Site Number :1001001	Sofia
Bulgaria	Investigational Site Number :1001002	Sofia
Bulgaria	Investigational Site Number :1001009	Sofia
Bulgaria	Investigational Site Number :1001005	Stara Zagora
Bulgaria	Investigational Site Number :1001010	Troyan
Canada	Investigational Site Number :1240002	Burlington	Ontario
Canada	Investigational Site Number :1240015	Edmonton	Alberta
Canada	Investigational Site Number :1240021	Edmonton	Alberta
Canada	Investigational Site Number :1240001	Montreal	Quebec
Canada	Investigational Site Number :1240003	Montreal	Quebec
Canada	Investigational Site Number :1240009	Montreal	Quebec
Canada	Investigational Site Number :1240004	Quebec
Canada	Investigational Site Number :1240005	Quebec
Canada	Investigational Site Number :1240018	Quebec
Canada	Investigational Site Number :1240019	Quebec
Canada	Investigational Site Number :1240010	Sherbrooke	Quebec
Canada	Investigational Site Number :1240011	Sherbrooke	Quebec
Canada	Investigational Site Number :1240016	Sherwood Park	Alberta
Canada	Investigational Site Number :1240006	St-charles Borrommee	Quebec
Canada	Investigational Site Number :1240012	Toronto	Ontario
Canada	Investigational Site Number :1240008	Trois-Rivieres	Quebec
Canada	Investigational Site Number :1240007	Vancouver	British Columbia
Canada	Investigational Site Number :1240017	Vancouver	British Columbia
Canada	Investigational Site Number :1240020	Victoriaville	Quebec
Canada	Investigational Site Number :1240013	Windsor	Ontario
Chile	Investigational Site Number :1520006	Curicó	Maule
Chile	Investigational Site Number :1520004	Quillota	Valparaíso
Chile	Investigational Site Number :1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520003	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520005	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520008	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520009	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520001	Talca	Maule
China	Investigational Site Number :1560037	Baotou
China	Investigational Site Number :1560006	Beijing
China	Investigational Site Number :1560003	Changchun
China	Investigational Site Number :1560021	Changsha
China	Investigational Site Number :1560022	Changsha
China	Investigational Site Number :1560001	Chengdu
China	Investigational Site Number :1560017	Chengdu
China	Investigational Site Number :1560005	Chongqing
China	Investigational Site Number :1560012	Chongqing
China	Investigational Site Number :1560053	Fuzhou
China	Investigational Site Number :1560019	Guangzhou
China	Investigational Site Number :1560036	Guangzhou
China	Investigational Site Number :1560018	Haikou
China	Investigational Site Number :1560045	Haikou
China	Investigational Site Number :1560046	Hangzhou
China	Investigational Site Number :1560009	Hefei
China	Investigational Site Number :1560041	Hefei
China	Investigational Site Number :1560008	Hohhot
China	Investigational Site Number :1560015	Hohhot
China	Investigational Site Number :1560027	Nanchang
China	Investigational Site Number :1560034	Nanjing
China	Investigational Site Number :1560007	Shanghai
China	Investigational Site Number :1560013	Shanghai
China	Investigational Site Number :1560032	Shanghai
China	Investigational Site Number :1560004	Shenyang
China	Investigational Site Number :1560014	Shenyang
China	Investigational Site Number :1560051	Shenzhen
China	Investigational Site Number :1560016	Shijiazhuang
China	Investigational Site Number :1560024	Taiyuan
China	Investigational Site Number :1560010	Tianjin
China	Investigational Site Number :1560028	Urumchi
China	Investigational Site Number :1560052	Wuhan
China	Investigational Site Number :1560020	Xi'An
China	Investigational Site Number :1560054	Xuzhou
China	Investigational Site Number :1560011	Yangzhou
China	Investigational Site Number :1560031	Zhanjiang
China	Investigational Site Number :1560002	Zhengzhou
Czechia	Investigational Site Number :2030002	Jindrichuv Hradec III
Czechia	Investigational Site Number :2030005	Karlovy Vary
Czechia	Investigational Site Number :2030009	Miroslav
Czechia	Investigational Site Number :2030001	Novy Bor
Czechia	Investigational Site Number :2030003	Praha 4
Czechia	Investigational Site Number :2030008	Praha 6 - Brevnov
Czechia	Investigational Site Number :2030004	Rokycany
Czechia	Investigational Site Number :2030006	Strakonice
Denmark	Investigational Site Number :2080003	Ålborg
Denmark	Investigational Site Number :2080001	Copenhagen Nv
Denmark	Investigational Site Number :2080002	Hvidovre
Denmark	Investigational Site Number :2080006	Naestved
Denmark	Investigational Site Number :2080005	Odense C
Denmark	Investigational Site Number :2080004	Roskilde
Denmark	Investigational Site Number :2080007	Vejle
Finland	Investigational Site Number :2460003	Pori
Finland	Investigational Site Number :2460001	Turku
Germany	Investigational Site Number :2760006	Berlin
Germany	Investigational Site Number :2760009	Frankfurt am Main
Germany	Investigational Site Number :2760002	Hamburg
Germany	Investigational Site Number :2760007	Koblenz
Germany	Investigational Site Number :2760011	Leipzig
Germany	Investigational Site Number :2760010	Lübeck
Germany	Investigational Site Number :2760008	Marburg
Hungary	Investigational Site Number :3480007	Balassagyarmat
Hungary	Investigational Site Number :3480011	Budapest
Hungary	Investigational Site Number :3480008	Edelény
Hungary	Investigational Site Number :3480001	Gödöllö
Hungary	Investigational Site Number :3480010	Hajdunánás
Hungary	Investigational Site Number :3480002	Komarom
Hungary	Investigational Site Number :3480003	Makó
Hungary	Investigational Site Number :3480006	Mohács
Hungary	Investigational Site Number :3480012	Puspokladany
Hungary	Investigational Site Number :3480004	Százhalombatta
Hungary	Investigational Site Number :3480005	Szombathely
Israel	Investigational Site Number :3760006	Ashkelon
Israel	Investigational Site Number :3760007	Beer Sheva
Israel	Investigational Site Number :3760003	Haifa
Israel	Investigational Site Number :3760004	Jerusalem
Israel	Investigational Site Number :3760005	Jerusalem
Israel	Investigational Site Number :3760001	Petah-Tikva
Israel	Investigational Site Number :3760002	Rehovot
Italy	Investigational Site Number :3800004	Cona	Ferrara
Italy	Investigational Site Number :3800007	Pisa
Italy	Investigational Site Number :3800001	Reggio Emilia
Italy	Investigational Site Number :3800005	Roma
Italy	Investigational Site Number :3800003	Rozzano	Milano
Japan	Investigational Site Number :3920005	Chuo-ku	Tokyo
Japan	Investigational Site Number :3920008	Chuo-ku	Tokyo
Japan	Investigational Site Number :3920030	Chuo-ku	Tokyo
Japan	Investigational Site Number :3920021	Hamamatsu-shi	Shizuoka
Japan	Investigational Site Number :3920023	Higashiibaraki-gun	Ibaraki
Japan	Investigational Site Number :3920011	Himeji-shi	Hyogo
Japan	Investigational Site Number :3920003	Joyo-shi	Kyoto
Japan	Investigational Site Number :3920013	Kasuga-shi	Fukuoka
Japan	Investigational Site Number :3920018	Kawachinagano-shi	Osaka
Japan	Investigational Site Number :3920001	Kishiwada-shi	Osaka
Japan	Investigational Site Number :3920015	Kokubunji-shi	Tokyo
Japan	Investigational Site Number :3920017	Kyoto-shi	Kyoto
Japan	Investigational Site Number :3920014	Naka-gun	Ibaraki
Japan	Investigational Site Number :3920028	Osaka-shi	Osaka
Japan	Investigational Site Number :3920012	Sakai-shi	Osaka
Japan	Investigational Site Number :3920016	Shinagawa-ku	Tokyo
Japan	Investigational Site Number :3920019	Takamatsu-shi	Kagawa
Japan	Investigational Site Number :3920004	Toshima-ku	Tokyo
Japan	Investigational Site Number :3920026	Toshima-ku	Tokyo
Japan	Investigational Site Number :3920006	Ueda-shi	Nagano
Japan	Investigational Site Number :3920029	Urasoe-shi	Okinawa
Japan	Investigational Site Number :3920027	Yokohama-shi	Kanagawa
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 :4100007	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100009	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100003	Wonju	Gangwon-do
Mexico	Investigational Site Number :4840004	Chihuahua
Mexico	Investigational Site Number :4840003	Durango
Mexico	Investigational Site Number :4840002	Guadalajara	Jalisco
Mexico	Investigational Site Number :4840006	Mexico Distrito Federal
Mexico	Investigational Site Number :4840001	Monterrey	Nuevo León
Mexico	Investigational Site Number :4840007	Oaxaca
Mexico	Investigational Site Number :4840005	Veracruz
Poland	Investigational Site Number :6160008	Bialystok	Podlaskie
Poland	Investigational Site Number :6160014	Elblag	Pomorskie
Poland	Investigational Site Number :6160015	Grodzisk Mazowiecki	Mazowieckie
Poland	Investigational Site Number :6160009	Grudziadz	Kujawsko-pomorskie
Poland	Investigational Site Number :6160011	Katowice	Slaskie
Poland	Investigational Site Number :6160007	Krakow	Malopolskie
Poland	Investigational Site Number :6160006	Poznan	Wielkopolskie
Poland	Investigational Site Number :6160016	Poznan	Wielkopolskie
Poland	Investigational Site Number :6160012	Warszawa	Mazowieckie
Romania	Investigational Site Number :6420001	Bucharest
Romania	Investigational Site Number :6420008	Bucuresti
Romania	Investigational Site Number :6420009	Bucuresti
Romania	Investigational Site Number :6420003	Cluj-Napoca
Romania	Investigational Site Number :6420004	Cluj-Napoca
Romania	Investigational Site Number :6420007	Constanta
Romania	Investigational Site Number :6420006	Timisoara
Romania	Investigational Site Number :6420010	Timisoara
Russian Federation	Investigational Site Number :6430003	Chelyabinsk
Russian Federation	Investigational Site Number :6430004	Kazan
Russian Federation	Investigational Site Number :6430001	Moscow
Russian Federation	Investigational Site Number :6430002	Moscow
Russian Federation	Investigational Site Number :6430005	Moscow
Russian Federation	Investigational Site Number :6430006	Moscow
Russian Federation	Investigational Site Number :6430008	Moscow
Russian Federation	Investigational Site Number :6430009	Moscow
Russian Federation	Investigational Site Number :6430007	St-Petersburg
Slovakia	Investigational Site Number :7030007	Banska Bystrica
Slovakia	Investigational Site Number :7030006	Humenne
Slovakia	Investigational Site Number :7030003	Levice
Slovakia	Investigational Site Number :7030001	Poprad
Slovakia	Investigational Site Number :7030002	Spisska Nova Ves
Spain	Investigational Site Number :7240002	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240003	Madrid
Spain	Investigational Site Number :7240001	Málaga
Spain	Investigational Site Number :7240005	Mérida / Badajoz	Extremadura
Spain	Investigational Site Number :7240010	Palma de Mallorca
Spain	Investigational Site Number :7240006	Pozuelo de Alarcón	Madrid
Spain	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 :7240004	Valencia
Sweden	Investigational Site Number :7520001	Lund
Sweden	Investigational Site Number :7520002	Stockholm
Turkey	Investigational Site Number :7920004	Ankara
Turkey	Investigational Site Number :7920001	Istanbul
Turkey	Investigational Site Number :7920006	Izmir
Turkey	Investigational Site Number :7920007	Izmir
Turkey	Investigational Site Number :7920008	Kirikkale
Turkey	Investigational Site Number :7920005	Manisa
Turkey	Investigational Site Number :7920002	Mersin
Ukraine	Investigational Site Number :8040003	Chernivtsi
Ukraine	Investigational Site Number :8040001	Ivano-Frankivsk
Ukraine	Investigational Site Number :8040006	Kharkiv
Ukraine	Investigational Site Number :8040004	Kyiv
Ukraine	Investigational Site Number :8040009	Odesa
Ukraine	Investigational Site Number :8040002	Ternopil
Ukraine	Investigational Site Number :8040005	Vinnytsya
Ukraine	Investigational Site Number :8040007	Zhytomyr
United States	SEC Clinical Research, LLC-Site Number:8400030	Andalusia	Alabama
United States	Michigan Medicine (University of Michigan)-Site Number:8400050	Ann Arbor	Michigan
United States	Johns Hopkins University (Asthma and Allergy Center)-Site Number:8400012	Baltimore	Maryland
United States	Clinical Research Center of Alabama, LLC-Site Number:8400041	Birmingham	Alabama
United States	UAB Lung Health Center-Site Number:8400013	Birmingham	Alabama
United States	Va Western New York Healthcare-Site Number:8400067	Buffalo	New York
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	American Health Research-Site Number:8400061	Charlotte	North Carolina
United States	Jefferson Associates in Internal Medicine-Site Number:8400037	Clairton	Pennsylvania
United States	Clinical Research Of West Florida Inc-Site Number:8400010	Clearwater	Florida
United States	Asthma and Allergy Associates, PC-Site Number:8400034	Colorado Springs	Colorado
United States	VitaLink research-Hamilton Mill-Site Number:8400055	Dacula	Georgia
United States	Midwest Pulmonary and Sleep Research Center-Site Number:8400040	Dayton	Ohio
United States	SEC Clinical Research, LLC-Site Number:8400059	Dothan	Alabama
United States	Aventiv Research, Inc-Site Number:8400024	Dublin	Ohio
United States	Duke Asthma, Allergy and Airway Center-Site Number:8400064	Durham	North Carolina
United States	VitaLink Research-Easley-Site Number:8400022	Easley	South Carolina
United States	OK Clinical Research-Site Number:8400005	Edmond	Oklahoma
United States	Clinical Trials Center of Middle Tennessee-Site Number:8400073	Franklin	Tennessee
United States	VitaLink Research- Gaffney-Site Number:8400047	Gaffney	South Carolina
United States	Finlay Medical Research-Site Number:8400014	Greenacres City	Florida
United States	Allergy, Asthma & Sinus Center, S.C.-Site Number:8400008	Greenfield	Wisconsin
United States	VitaLink Research-Greenville-Site Number:8400007	Greenville	South Carolina
United States	Bayer College of Medicine-Site Number:8400018	Houston	Texas
United States	Sierra Clinical Research-Site Number:8400035	Las Vegas	Nevada
United States	DC Research Works-Site Number:8400016	Marietta	Georgia
United States	Metroplex Pulmonary and Sleep Center-Site Number:8400021	McKinney	Texas
United States	Velocity Clinical Research, Medford-Site Number:8400001	Medford	Oregon
United States	Finlay Medical Research-Site Number:8400062	Miami	Florida
United States	Project 4 research, Inc.-Site Number:8400023	Miami	Florida
United States	Pulmonary Associates of Mobile, P.C.-Site Number:8400057	Mobile	Alabama
United States	Clinical Research of Charleston-Site Number:8400044	Mount Pleasant	South Carolina
United States	IMA Clinical Research, LLC-Site Number:8400070	New York	New York
United States	Renstar Medical Research-Site Number:8400051	Ocala	Florida
United States	Florida Institute for Clinical Research, LLC-Site Number:8400029	Orlando	Florida
United States	Emerald Coast Research Associates-Site Number:8400032	Panama City	Florida
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	Mayo Clinic Lanmark Center 2-46-Site Number:8400065	Rochester	Minnesota
United States	Clinical Research of Rock Hill-Site Number:8400046	Rock Hill	South Carolina
United States	Midwest Chest Consultants, P.C.-Site Number:8400011	Saint Charles	Missouri
United States	Washington University School of Medicine-Site Number:8400004	Saint Louis	Missouri
United States	Sarasota Clinical Research-Site Number:8400026	Sarasota	Florida
United States	Sherman Clinical Research-Site Number:8400027	Sherman	Texas
United States	VitaLink Research - Spartanburg-Site Number:8400048	Spartanburg	South Carolina
United States	MultiCare Institute for Research and Innovation-Site Number:8400036	Tacoma	Washington
United States	Asthma Allergy & Sinus Center-Site Number:8400038	White Marsh	Maryland
United States	Accellacare-Site Number:8400052	Wilmington	North Carolina
United States	Southeastern Research Center-Site Number:8400060	Winston-Salem	North Carolina
United States	North Georgia Clinical Research-Site Number:8400025	Woodstock	Georgia
United States	Berks Schuylkill Respiratory Specialists, LTD-Site Number:8400063	Wyomissing	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Canada,  Chile,  China,  Czechia,  Denmark,  Finland,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Romania,  Russian Federation,  Slovakia,  Spain,  Sweden,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-Week Treatment Period	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.	Baseline (Day 1) to Week 52
Secondary	Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) at 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.	Baseline (Day 1) to Week 12
Secondary	Change From Baseline in Pre-BD FEV1 at 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.	Baseline (Day 1) to Week 52
Secondary	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)	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.	Baseline (Day 1) to Week 12
Secondary	Change From Baseline in Pre-BD FEV1 at Week 52 in Subgroup of Participants With Baseline FeNO >=20 Ppb	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.	Baseline (Day 1) to Week 52
Secondary	Change From Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) Total Score at 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.	Baseline (Day 1) to Week 52
Secondary	Percentage of Participants With SGRQ Improvement >=4 Points at 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.	Baseline (Day 1) to Week 52
Secondary	Change From Baseline in Evaluating Respiratory Symptoms (E-RS) in COPD (E-RS: COPD) RS-Total Score at 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.	Baseline (Day 1) to Week 52
Secondary	Annualized Rate of Moderate or Severe COPD Exacerbation Over the 52-Week Treatment Period in Subgroup of Participants With Baseline FeNO >=20 Ppb	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.	Baseline (Day 1) to Week 52
Secondary	Change From Baseline in Pre-BD FEV1 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.	Baseline (Day 1) to Weeks 2, 4, 8, 24, 36 and 44
Secondary	Change From Baseline in Post-BD FEV1 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.	Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36 and 52
Secondary	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	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.	Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36, 44 and 52
Secondary	Change From Baseline in Post-BD FEF 25-75% 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.	Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36 and 52
Secondary	Annualized Rate of Severe COPD Exacerbations Over the 52-Week Treatment Period	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.	Baseline (Day 1) to Week 52
Secondary	Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period	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.	Baseline (Day 1) and up to Weeks 12, 24, 36 and 52
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	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.	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
Secondary	Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab	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.	Up to Week 52