Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (AERIFY-2)

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

Randomized, Double-blind, Placebo-controlled, Parallel-group Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of SAR440340/ REGN3500/ Itepekimab (Anti-IL-33 mAb) in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04751487
• Other study ID #: EFC16819
• Secondary ID: U1111-1250-28432
• Status: Recruiting
• Phase: Phase 3
• Start date: February 12, 2021
• Est. completion date: October 17, 2025

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free number for US &
• Phone: 800-633-1610
• Email: contact-us[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

Primary population (former smokers cohort):

• Evaluate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate-or-severe COPD exacerbations in former smokers with moderate-to-severe COPD

Secondary Objectives:

Primary population (former smokers cohort):

• Evaluate the efficacy of itepekimab compared with placebo on pulmonary function in former smokers with moderate-to-severe COPD

• Evaluate the efficacy of itepekimab compared with placebo on occurrence of acute exacerbation of COPD (AECOPD) in former smokers with moderate-to-severe COPD

• Evaluate the efficacy of itepekimab compared with placebo on severe AECOPD in former smokers with moderate-to-severe COPD

• Evaluate the efficacy of itepekimab compared with placebo on corticosteroid-treated AECOPD in former smokers with moderate-to-severe COPD

• Evaluate the efficacy of itepekimab compared with placebo on respiratory symptoms in former smokers with moderate-to-severe COPD

• Evaluate the efficacy of itepekimab compared with placebo on Forced Expiratory Volume in 1 second (FEV1) slope in former smokers with moderate-to-severe COPD

• Evaluate the efficacy of itepekimab compared with placebo on health-related quality of life (HRQoL) as assessed by St. George's Respiratory Questionnaire (SGRQ) in former smokers with moderate-to-severe COPD

• Evaluate the safety and tolerability of itepekimab in former smokers with moderate-to-severe COPD

• Evaluate the pharmacokinetic (PK) profile of itepekimab in former smokers with moderate-to-severe COPD

• Evaluate immunogenicity to itepekimab in former smokers with moderate-to-severe COPD

Secondary population (current smokers cohort)

• Estimate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate or severe COPD exacerbations in current smokers with moderate-to-severe COPD

• Estimate the efficacy of itepekimab compared with placebo on pulmonary function in current smokers with moderate-to-severe COPD

• Estimate the safety and tolerability of itepekimab in current smokers with moderate-to-severe COPD

• Estimate the PK profile of itepekimab in current smokers with moderate to severe COPD

• Estimate immunogenicity to itepekimab in current smokers with moderate-to-severe COPD

Description:

The study duration per participant:

• Screening period is 3-5 weeks

• Randomized investigational medicinal product (IMP) treatment period is 52 weeks for first cohort of randomized former smoker participants [approximately 930] and cohort of current smokers [approximately 280], and 24 to 52 weeks for potential additional randomized former smoker participants

• Post-IMP treatment follow-up period is 20 weeks for participants not transitioning to the extension study LTS18133 Note: A long-term, double-blinded extension study (LTS18133) will be implemented to allow participants in this study to continue receiving active IMP for an additional period. Only participants completing their End-of-Treatment (EOT) visit per this study protocol will be offered to participate in the LTS18133 study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1210
• Est. completion date: October 17, 2025
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

Inclusion criteria :

• Participant must be 40 to 85 years of age inclusive.

• Physician diagnosis of COPD for at least 1 year (based on Global Initiative for Chronic Obstructive Lung Disease [GOLD] definition).

• Smoking history of =10 pack-years:

• For former smokers: participants who report that they are not currently smoking and smoking cessation must have occurred =6 months prior to Screening (Visit 1A) with an intention to quit permanently.

• For current smokers: participants who report that they are currently smoking tobacco (participant smoked at least 1 cigarette per day on average during the past 7 days) at Screening (Visit 1A) and who are not currently participating in or planning to initiate a smoking cessation intervention at Screening (Visit 1A) or during Screening period.

• Participants with moderate-to-severe COPD

• Participant-reported history of signs and symptoms of chronic bronchitis (chronic productive cough for at least 3 months in the year prior to Screening in a participant in whom other causes of chronic cough [eg, inadequately treated gastroesophageal reflux or chronic rhinosinusitis; or clinical diagnosis of bronchiectasis] has been excluded).

• Documented history of high exacerbation risk defined as having had =2 moderate or =1 severe exacerbations within the year prior to Screening (Visit 1A), with at least 1 exacerbation treated with systemic corticosteroids. At least one exacerbation must have occurred while participants were on their current controller therapy:

• Moderate exacerbations will be recorded by the Investigator and are defined as acute worsening of respiratory symptoms that requires either systemic corticosteroids (IM, IV, or oral) and/or antibiotics.

• Severe exacerbations will be recorded by the Investigator and are defined as AECOPD that require hospitalization or observation for >24 hours in emergency department/urgent care facility.

• Participants with standard of care controller therapy, for =3 months prior to Screening (Visit 1A) and at a stable dose of controller therapy for at least 1 month prior to the Screening, including either: inhaled corticosteroid (ICS) + long-acting beta-agonist (LABA), long-acting muscarinic antagonist (LAMA) + LABA or LAMA + LABA + ICS.

• Body mass index (BMI) =18.0 kg/m^2, or BMI =16.0 kg/m^2 for participants enrolled in East-Asian countries.

• Female participant is not pregnant, not breastfeeding, and at least one of the following conditions applies:

• not a women of child-bearing potential (WOCBP) OR

• a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 20 weeks after the last dose of study intervention. -

Exclusion criteria:

• Current diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines, or documented history of asthma unless asthma resolved before 18 years of age and has not recurred.

• For former smokers: Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit 1A).

• For current smokers: vaping of any products (eg, nicotine, THC) within 6 months prior to Screening (Visit 1A).

• Clinically significant new abnormal electrocardiogram (ECG) within 6 months prior to, or at Screening (Visit 1A) that may affect the participant's participation in the study.

• Clinically significant and current pulmonary disease other than COPD, eg, sarcoidosis, interstitial lung disease, bronchiectasis (clinical diagnosis), diagnosis of a-1 anti-trypsin deficiency, or another diagnosed pulmonary disease.

• Diagnosis of cor pulmonale, evidence of right cardiac failure, or moderate-to-severe pulmonary hypertension.

• Hypercapnia requiring bilevel positive airway pressure (BiPAP).

• Moderate or severe exacerbation of COPD (AECOPD) within 4 weeks prior to Screening (Visit 1A).

• Prior history of / planned: lung pneumonectomy for any reason, or lung volume reduction procedures (including bronchoscopic volume reduction) for COPD. Note: Surgical biopsy, or segmentectomy, or wedge resection, or lobectomy for other diseases would not be excluded.

• Unstable ischemic heart disease, including acute myocardial infarction within the past 1 year prior to Screening, or unstable angina in the 6 months prior to Screening (Visit 1A).

• Cardiac arrhythmias including paroxysmal (eg, intermittent) atrial fibrillation.

• Uncontrolled hypertension (ie, systolic blood pressure [BP] >180 mm Hg or diastolic BP >110 mm Hg with or without use of anti-hypertensive therapy).

• Participants with active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection (TBI), or who are at high risk of contracting TB (such as close contact with individuals with active or latent TB) or received Bacillus Calmette-Guérin (BCG)-vaccination within 12 weeks prior to Screening (Visit 1A).

• History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening (Visit 1A).

• Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection or in contact with known exposure to COVID-19 at Screening (Visit 1A); known history of COVID-19 infection within 4 weeks prior to Screening (Visit 1A); history of requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO) secondary to COVID-19 within 3 months prior to Screening (Visit 1A); participants who have had a COVID-19 infection prior Screening (Visit 1A) who have not yet sufficiently recovered to participate in the procedures of a clinical trial.

• Evidence of acute or chronic infection requiring systemic treatment with antibacterial, antiviral, antifungal, antiparasitic, or antiprotozoal medications within 4 weeks before Screening (Visit 1A), significant viral infections within 4 weeks before Screening (Visit 1A) that may not have been treated with antiviral treatment (eg, influenza receiving only symptomatic treatment).

• Participants with active autoimmune disease or participants using immunosuppressive therapy for autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis.

• History of malignancy within 5 years before Screening (Visit 1A), except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.

• Previous use of itepekimab.

The above information is 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
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Itepekimab SAR440340
Pharmaceutical form: solution for injection in pre-filled syringe Route of administration: subcutaneous
• Placebo
Pharmaceutical form: solution for injection in pre-filled syringe Route of administration: subcutaneous

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320009	Berazategui	Buenos Aires
Argentina	Investigational Site Number : 0320006	Buenos Aires	Ciudad De Buenos Aires
Argentina	Investigational Site Number : 0320001	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320008	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320005	Pergamino	Buenos Aires
Argentina	Investigational Site Number : 0320003	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320004	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320007	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320002	Vicente Lopez	Ciudad De Buenos Aires
Brazil	Santa Casa de Belo Horizonte - Hospital Emygdio Germano Site Number : 0760014	Belo Horizonte	Minas Gerais
Brazil	Faculdade de Medicina da Universidade Estadual Paulista Site Number : 0760005	Botucatu	São Paulo
Brazil	CECAP - Centro de Cardiologia Clinica e Pesquisa Dra. Juliana Souza Site Number : 0760018	Brasilia	Distrito Federal
Brazil	PUC Campinas - Sociedade Campineira de Educaçao e Instruçao Site Number : 0760010	Campinas	São Paulo
Brazil	CETI - Centro de Estudos em Terapias Inovadoras Site Number : 0760012	Curitiba	Paraná
Brazil	Hospital Nossa Senhora da Conceicao - Grupo Hospitalar Conceicao Site Number : 0760006	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Sao Lucas da PUCRS Site Number : 0760007	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Ceos Site Number : 0760021	Porto Alegre	Rio Grande Do Sul
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre Site Number : 0760001	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Brasil de Pesquisa Clínica-IBPCLIN S/A Site Number : 0760017	Rio de Janeiro
Brazil	SER da Bahia Site Number : 0760020	Salvador	Bahia
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clinicos Site Number : 0760015	Sao Bernardo do Campo	São Paulo
Brazil	Hospital Sao Domingos Site Number : 0760016	Sao Luis	Maranhão
Brazil	CEPIC - Centro Paulista de Investigação Clínica Site Number : 0760004	Sao Paulo
Brazil	Nucleo de Pesquisa Clinica e Ensino da Rede Sao Camilo Site Number : 0760013	Sao Paulo	São Paulo
Brazil	Clinica de Alergia Martti Antila Site Number : 0760008	Sorocaba	São Paulo
Brazil	CEDOES - Centro de Diagnostico e Pesquisa de Osteoporose do ES Site Number : 0760009	Vitoria	Espírito Santo
Bulgaria	Investigational Site Number : 1000008	Blagoevgrad
Bulgaria	Investigational Site Number : 1000013	Dupnitsa
Bulgaria	Investigational Site Number : 1000004	Gabrovo
Bulgaria	Investigational Site Number : 1000009	Haskovo
Bulgaria	Investigational Site Number : 1000005	Montana
Bulgaria	Investigational Site Number : 1000002	Plovdiv
Bulgaria	Investigational Site Number : 1000003	Ruse
Bulgaria	Investigational Site Number : 1000012	Ruse
Bulgaria	Investigational Site Number : 1000001	Sofia
Bulgaria	Investigational Site Number : 1000006	Sofia
Canada	Investigational Site Number : 1240021	Ajax	Ontario
Canada	Investigational Site Number : 1240020	Burlington	Ontario
Canada	Investigational Site Number : 1240023	Guelph	Ontario
Canada	Investigational Site Number : 1240014	Kelowna	British Columbia
Canada	Investigational Site Number : 1240012	Moncton	New Brunswick
Canada	Investigational Site Number : 1240016	Penticton	British Columbia
Canada	Investigational Site Number : 1240003	Quebec
Canada	Investigational Site Number : 1240004	Sherbrooke	Quebec
Canada	Investigational Site Number : 1240006	Sherwood Park	Alberta
Canada	Investigational Site Number : 1240005	St-charles Borrommee	Quebec
Canada	Investigational Site Number : 1240019	Terrebonne	Quebec
Canada	Investigational Site Number : 1240009	Toronto	Ontario
Canada	Investigational Site Number : 1240001	Trois-Rivieres	Quebec
Canada	Investigational Site Number : 1240002	Victoriaville	Quebec
Canada	Investigational Site Number : 1240018	Windsor	Ontario
Canada	Investigational Site Number : 1240022	Windsor	Ontario
Chile	Investigational Site Number : 1520006	Quillota	Valparaíso
Chile	Investigational Site Number : 1520001	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 : 1520007	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520008	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520002	Talca	Maule
Chile	Investigational Site Number : 1520009	Valdivia	Los Ríos
Czechia	Investigational Site Number : 2030001	Jindrichuv Hradec III
Czechia	Investigational Site Number : 2030009	Mesice
Czechia	Investigational Site Number : 2030005	Mlada Boleslav
Czechia	Investigational Site Number : 2030008	Olomouc
Czechia	Investigational Site Number : 2030004	Ostrava
Czechia	Investigational Site Number : 2030002	Praha 4
Czechia	Investigational Site Number : 2030006	Teplice
Czechia	Investigational Site Number : 2030007	Varnsdorf
Denmark	Investigational Site Number : 2080001	Hvidovre
Denmark	Investigational Site Number : 2080003	Vejle
Estonia	Investigational Site Number : 2330001	Tartu
France	Investigational Site Number : 2500006	Angers
France	Investigational Site Number : 2500001	Lyon
France	Investigational Site Number : 2500002	Montpellier
France	Investigational Site Number : 2500007	Paris
France	Investigational Site Number : 2500003	Pessac
France	Investigational Site Number : 2500004	Reims
Georgia	Investigational Site Number : 2680003	Batumi
Georgia	Investigational Site Number : 2680001	Tbilisi
Georgia	Investigational Site Number : 2680002	Tbilisi
Germany	Investigational Site Number : 2760004	Berlin
Germany	Investigational Site Number : 2760009	Berlin
Germany	Investigational Site Number : 2760010	Berlin
Germany	Investigational Site Number : 2760005	Frankfurt am Main
Germany	Investigational Site Number : 2760002	Hamburg
Germany	Investigational Site Number : 2760014	Hannover
Germany	Investigational Site Number : 2760006	Koblenz
Germany	Investigational Site Number : 2760007	Leipzig
Germany	Investigational Site Number : 2760008	Leipzig
Germany	Investigational Site Number : 2760003	Lübeck
Germany	Investigational Site Number : 2760001	Mainz
Germany	Investigational Site Number : 2760012	Neu-Isenburg
Germany	Investigational Site Number : 2760011	Rosenheim
Hungary	Investigational Site Number : 3480002	Balassagyarmat
Hungary	Investigational Site Number : 3480009	Budapest
Hungary	Investigational Site Number : 3480013	Budapest
Hungary	Investigational Site Number : 3480005	Edelény
Hungary	Investigational Site Number : 3480004	Hajdunánás
Hungary	Investigational Site Number : 3480003	Puspokladany
Hungary	Investigational Site Number : 3480001	Százhalombatta
Hungary	Investigational Site Number : 3480012	Szombathely
India	Investigational Site Number : 3560016	Belgaum
India	Investigational Site Number : 3560001	Chandigarh
India	Investigational Site Number : 3560014	India
India	Investigational Site Number : 3560013	Jaipur
India	Investigational Site Number : 3560019	Kanpur
India	Investigational Site Number : 3560010	Kolkata
India	Investigational Site Number : 3560005	Nagpur
India	Investigational Site Number : 3560017	Nagpur
India	Investigational Site Number : 3560009	Nashik
India	Investigational Site Number : 3560012	Pune
India	Investigational Site Number : 3560018	Pune
Israel	Investigational Site Number : 3760002	Jerusalem
Israel	Investigational Site Number : 3760003	Jerusalem
Israel	Investigational Site Number : 3760001	Petah-Tikva
Israel	Investigational Site Number : 3760009	Ramat Gan
Israel	Investigational Site Number : 3760004	Rehovot
Japan	Investigational Site Number : 3920017	Chuo-ku	Tokyo
Japan	Investigational Site Number : 3920024	Chuo-ku	Tokyo
Japan	Investigational Site Number : 3920040	Chuo-ku	Tokyo
Japan	Investigational Site Number : 3920005	Fukuoka-shi	Fukuoka
Japan	Investigational Site Number : 3920027	Fukuoka-shi	Fukuoka
Japan	Investigational Site Number : 3920002	Hamamatsu-shi	Shizuoka
Japan	Investigational Site Number : 3920028	Hamamatsu-shi	Shizuoka
Japan	Investigational Site Number : 3920013	Himeji-shi	Hyogo
Japan	Investigational Site Number : 3920010	Hiroshima-shi	Hiroshima
Japan	Investigational Site Number : 3920034	Ikoma-shi	Nara
Japan	Investigational Site Number : 3920019	Itabashi-ku	Tokyo
Japan	Investigational Site Number : 3920033	Kawasaki-shi	Kanagawa
Japan	Investigational Site Number : 3920029	Kiyose-City	Tokyo
Japan	Investigational Site Number : 3920011	Konan-ku, Yokohama-shi	Kanagawa
Japan	Investigational Site Number : 3920021	Kure-shi	Hiroshima
Japan	Investigational Site Number : 3920035	Kure-shi	Hiroshima
Japan	Investigational Site Number : 3920030	Kurume-shi	Fukuoka
Japan	Investigational Site Number : 3920043	Matsusaka-shi	Mie
Japan	Investigational Site Number : 3920001	Meguro-ku	Tokyo
Japan	Investigational Site Number : 3920015	Mizunami-shi	Gifu
Japan	Investigational Site Number : 3920020	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920023	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920003	Osaka-shi	Osaka
Japan	Investigational Site Number : 3920026	Osaka-shi	Osaka
Japan	Investigational Site Number : 3920007	Sakai-shi	Osaka
Japan	Investigational Site Number : 3920009	Sakaide-shi	Kagawa
Japan	Investigational Site Number : 3920036	Sano-shi	Tochigi
Japan	Investigational Site Number : 3920038	Sapporo-shi	Hokkaido
Japan	Investigational Site Number : 3920042	Sapporo-shi	Hokkaido
Japan	Investigational Site Number : 3920025	Shibuya-ku	Tokyo
Japan	Investigational Site Number : 3920016	Shinagawa-ku	Tokyo
Japan	Investigational Site Number : 3920037	Shinagawa-ku	Tokyo
Japan	Investigational Site Number : 3920014	Takamatsu-shi	Kagawa
Japan	Investigational Site Number : 3920041	Toshima-ku	Tokyo
Japan	Investigational Site Number : 3920032	Yanagawa-shi	Fukuoka
Japan	Investigational Site Number : 3920006	Yao-shi	Osaka
Japan	Investigational Site Number : 3920039	Yokohama-shi	Kanagawa
Korea, Republic of	Investigational Site Number : 4100003	Incheon	Incheon-gwangyeoksi
Korea, Republic of	Investigational Site Number : 4100005	Seongnam	Gyeonggi-do
Korea, Republic of	Investigational Site Number : 4100001	Seoul
Korea, Republic of	Investigational Site Number : 4100004	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100002	Wonju	Gangwon-do
Latvia	Investigational Site Number : 4280002	Daugavpils
Latvia	Investigational Site Number : 4280001	Riga
Lithuania	Investigational Site Number : 4400001	Kaunas
Lithuania	Investigational Site Number : 4400002	Kaunas
Lithuania	Investigational Site Number : 4400003	Klaipeda
Mexico	Investigational Site Number : 4840010	Aguascalientes
Mexico	Investigational Site Number : 4840003	Chihuahua
Mexico	Investigational Site Number : 4840007	Durango
Mexico	Investigational Site Number : 4840012	Durango, Durango
Mexico	Investigational Site Number : 4840006	Mexico City
Mexico	Investigational Site Number : 4840002	Monterrey	Nuevo León
Mexico	Investigational Site Number : 4840008	Monterrey	Nuevo León
Mexico	Investigational Site Number : 4840009	Monterrey	Nuevo León
Mexico	Investigational Site Number : 4840001	Monterrey, Nuevo León
Mexico	Investigational Site Number : 4840004	Veracruz
Mexico	Investigational Site Number : 4840015	Yucatan
Netherlands	Investigational Site Number : 5280005	Arnhem
Netherlands	Investigational Site Number : 5280001	Breda
Netherlands	Investigational Site Number : 5280006	Nijmegen
Netherlands	Investigational Site Number : 5280008	Zutphen
Netherlands	Investigational Site Number : 5280004	Zwolle
Norway	Investigational Site Number : 5780001	Lørenskog
Poland	Investigational Site Number : 6160008	Bialystok	Podlaskie
Poland	Investigational Site Number : 6160002	Katowice	Slaskie
Poland	Investigational Site Number : 6160003	Malbork	Pomorskie
Poland	Investigational Site Number : 6160009	Ostrowiec Swietokrzyski	Swietokrzyskie
Poland	Investigational Site Number : 6160005	Wolomin	Mazowieckie
Portugal	Investigational Site Number : 6200009	Almada
Portugal	Investigational Site Number : 6200006	Aveiro
Portugal	Investigational Site Number : 6200002	Braga
Portugal	Investigational Site Number : 6200004	Coimbra
Portugal	Investigational Site Number : 6200011	Guarda
Portugal	Investigational Site Number : 6200001	Guimarães
Portugal	Investigational Site Number : 6200010	Matosinhos
Portugal	Investigational Site Number : 6200003	Porto
Puerto Rico	Cardiopulmonary Research Site Number : 8400040	Guaynabo
Puerto Rico	BRCR Medical Center, Inc. Site Number : 8400190	Ponce
Puerto Rico	BRCR Medical Center Site Number : 8400180	San Juan
Puerto Rico	Inspire Pulmonary & Sleep Medicine Specialists Site Number : 8400232	Temecula
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 : 6430003	Saint-Petersburg
Russian Federation	Investigational Site Number : 6430004	St-Petersburg
Russian Federation	Investigational Site Number : 6430006	Ulyanovsk
South Africa	Investigational Site Number : 7100013	Benoni
South Africa	Investigational Site Number : 7100001	Cape Town
South Africa	Investigational Site Number : 7100002	Cape Town
South Africa	Investigational Site Number : 7100019	Cape Town
South Africa	Investigational Site Number : 7100015	Chatsworth
South Africa	Investigational Site Number : 7100005	Durban
South Africa	Investigational Site Number : 7100006	Durban
South Africa	Investigational Site Number : 7100016	Durban
South Africa	Investigational Site Number : 7100017	Durban
South Africa	Investigational Site Number : 7100004	Gatesville
South Africa	Investigational Site Number : 7100012	Middelburg
South Africa	Investigational Site Number : 7100003	Parow
South Africa	Investigational Site Number : 7100009	Pretoria
Spain	Investigational Site Number : 7240014	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240010	Cáceres
Spain	Investigational Site Number : 7240009	Lleida / Lleida	Lleida [Lérida]
Spain	Investigational Site Number : 7240003	Madrid
Spain	Investigational Site Number : 7240011	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240007	Madrid / Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240001	Málaga
Spain	Investigational Site Number : 7240002	Mérida / Badajoz	Extremadura
Spain	Investigational Site Number : 7240004	Palma de Mallorca	Balears [Baleares]
Spain	Investigational Site Number : 7240008	Pozuelo De Alarcón	Madrid
Spain	Investigational Site Number : 7240006	Sant Boi de Llobregat	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240013	Santander	Cantabria
Spain	Investigational Site Number : 7240012	Zaragoza
Turkey	Investigational Site Number : 7920007	Ankara
Turkey	Investigational Site Number : 7920005	Balcali Adana
Turkey	Investigational Site Number : 7920001	Istanbul
Turkey	Investigational Site Number : 7920003	Izmir
Turkey	Investigational Site Number : 7920006	Kirikkale
Turkey	Investigational Site Number : 7920002	Mersin
United Kingdom	Investigational Site Number : 8260003	Bradford
United Kingdom	Investigational Site Number : 8260002	Chertsey	Surrey
United Kingdom	Investigational Site Number : 8260005	Liverpool
United Kingdom	Investigational Site Number : 8260008	Milton Keynes
United Kingdom	Investigational Site Number : 8260001	Newcastle upon Tyne
United Kingdom	Investigational Site Number : 8260007	Tyne And Wear	North Tyneside
United Kingdom	Investigational Site Number : 8260006	Wishaw	Glasgow City
United States	Johns Hopkins Asthma and Allergy Center Site Number : 8400055	Baltimore	Maryland
United States	The Rheumatology and Pulmonary Clinic Site Number : 8400053	Beckley	West Virginia
United States	St. Luke's University Health Network Site Number : 8400187	Bethlehem	Pennsylvania
United States	TTS Research Site Number : 8400012	Boerne	Texas
United States	Care Access Site Number : 8400276	Boston	Massachusetts
United States	Care Access Site Number : 8400281	Boston	Massachusetts
United States	Helix Biomedics, LLC Site Number : 8400049	Boynton Beach	Florida
United States	Meris Clinical Research Site Number : 8400021	Brandon	Florida
United States	Smart Medical Research Site Number : 8400191	Brooklyn	New York
United States	VA Western New York Healthcare System Site Number : 8400050	Buffalo	New York
United States	Lowcountry Lung & Critical Care Site Number : 8400175	Charleston	South Carolina
United States	American Health Research Site Number : 8400002	Charlotte	North Carolina
United States	University of Cincinnati Site Number : 8400042	Cincinnati	Ohio
United States	Innovative Research of West Florida, Inc Site Number : 8400041	Clearwater	Florida
United States	Medtrial, LLC Site Number : 8400048	Columbia	South Carolina
United States	Remington-Davis Inc Site Number : 8400004	Columbus	Ohio
United States	Beautiful Minds Clinical Research Center Site Number : 8400352	Cutler Bay	Florida
United States	Omega Research Site Number : 8400031	DeBary	Florida
United States	Allianz Research Institute Colorado Site Number : 8400061	Denver	Colorado
United States	Henry Ford Hospital Site Number : 8400052	Detroit	Michigan
United States	Sciences Connections, LLC Site Number : 8400045	Doral	Florida
United States	OK Clinical Research LLC Site Number : 8400001	Edmond	Oklahoma
United States	Care Access Fairview Heights Site Number : 8400033	Fairview Heights	Illinois
United States	New York - Presbyterian Queens Site Number : 8400028	Flushing	New York
United States	Clinical Trials Center of Middle Tennessee Site Number : 8400025	Franklin	Tennessee
United States	UCSF Fresno Site Number : 8400030	Fresno	California
United States	VitaLink Research- Gaffney Site Number : 8400003	Gaffney	South Carolina
United States	North Florida/South Georgia Veterans Health System Site Number : 8400176	Gainesville	Florida
United States	Aurora BayCare Medical Center Site Number : 8400046	Green Bay	Wisconsin
United States	Finlay Medical Research Site Number : 8400011	Greenacres City	Florida
United States	Direct Helpers Medical Center Inc Site Number : 8400065	Hialeah	Florida
United States	United Memorial Medical Center (UMMC) Site Number : 8400193	Houston	Texas
United States	Advanced Respiratory and Sleep Medicine Site Number : 8400022	Huntersville	North Carolina
United States	Multi-Specialty Research Associates, Inc Site Number : 8400044	Lake City	Florida
United States	Radiance Clinical Research Site Number : 8400037	Lampasas	Texas
United States	Sierra Clinical Research Site Number : 8400005	Las Vegas	Nevada
United States	Revive Research Institute Site Number : 8400186	Lathrup Village	Michigan
United States	Lexington VA Health Care System Site Number : 8400036	Lexington	Kentucky
United States	Advanced Pulmonary Research Institute Site Number : 8400018	Loxahatchee Groves	Florida
United States	Columbus Clinical Services Site Number : 8400054	Miami	Florida
United States	Finlay Medical Research Site Number : 8400007	Miami	Florida
United States	MCR Research Site Number : 8400425	Miami	Florida
United States	My Community Research Center Site Number : 8400060	Miami	Florida
United States	Phoenix Medical Research Site Number : 8400019	Miami	Florida
United States	Y and L Advance Health Care, Inc D/B/A Elite Clinical Res Site Number : 8400009	Miami	Florida
United States	AES Salt Lake City Site Number : 8400332	Murray	Utah
United States	Rutgers Institute for Translational Medicine and Science/Rutgers University Site Number : 8400059	New Brunswick	New Jersey
United States	Captain James A. Lovell Federal Health Care Center Site Number : 8400032	North Chicago	Illinois
United States	Renstar Medical Research Site Number : 8400015	Ocala	Florida
United States	Central Florida Pulmonary Group, PA Site Number : 8400192	Orlando	Florida
United States	Heuer M.D. Research Site Number : 8400016	Orlando	Florida
United States	Oviedo Medical Research Site Number : 8400026	Oviedo	Florida
United States	Palmtree Clinical Research Site Number : 8400184	Palm Springs	California
United States	Innovation Medical Research Center Site Number : 8400067	Palmetto Bay	Florida
United States	Pines Care Research Center LLC Site Number : 8400056	Pembroke Pines	Florida
United States	Illinois Lung Institute Site Number : 8400024	Peoria	Illinois
United States	Temple University Hospital Site Number : 8400062	Philadelphia	Pennsylvania
United States	Synexus Phoenix Central (Central Phoenix Medical Clinic) Site Number : 8400333	Phoenix	Arizona
United States	Allegheny Health Network Site Number : 8400058	Pittsburgh	Pennsylvania
United States	Clincove: Plano Primary Care Clinic Site Number : 8400424	Plano	Texas
United States	Kaiser Permanente Center for Health Research Site Number : 8400039	Portland	Oregon
United States	Probe Clinical Research Corporation Site Number : 8400188	Riverside	California
United States	Washington University School of Medicine Site Number : 8400035	Saint Louis	Missouri
United States	Sun Research Institute Site Number : 8400183	San Antonio	Texas
United States	Sarasota Memorial Health Care System Clinical ResearchCenter Site Number : 8400178	Sarasota	Florida
United States	Schenectady Pulmonary and Critical Care Associates Site Number : 8400029	Schenectady	New York
United States	Pulmonary & Critical Care Site Number : 8400047	Shreveport	Louisiana
United States	Clinical Research of West Florida, Inc Site Number : 8400008	Tampa	Florida
United States	Genesis Clinical Research, LLC Site Number : 8400182	Tampa	Florida
United States	Toledo Institute of Clinical Research Site Number : 8400014	Toledo	Ohio
United States	Cotton O'Neil Garfield Site Number : 8400063	Topeka	Kansas
United States	Medster Research, LLC Site Number : 8400051	Valdosta	Georgia
United States	The Iowa Clinic Site Number : 8400034	West Des Moines	Iowa
United States	North Georgia Clinical Research Site Number : 8400013	Woodstock	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Canada,  Chile,  Czechia,  Denmark,  Estonia,  France,  Georgia,  Germany,  Hungary,  India,  Israel,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) in former smokers	Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) over the placebo-controlled treatment period.	Baseline up to End Of Treatment (EOT) (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)
Secondary	Change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) in former smokers	FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.	Baseline to Week 24
Secondary	Change from baseline in post-BD FEV1 in former smokers	FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.	Baseline to Week 24 and Week 52
Secondary	Change from baseline in pre-BD FEV1 in former smokers	FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.	Baseline to Week 52
Secondary	Time to first moderate or severe AECOPD in former smokers	Time to first moderate or severe AECOPD over the placebo-controlled treatment period.	Baseline through EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)
Secondary	Annualized rate of severe AECOPD in former smokers	Annualized rate of severe AECOPD over the placebo-controlled treatment period.	Baseline up to EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)
Secondary	Time to first severe AECOPD in former smokers	Time to first severe AECOPD over the placebo-controlled treatment period.	Baseline through EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)
Secondary	Annualized rate of corticosteroid-treated AECOPD in former smokers	Annualized rate of corticosteroid-treated AECOPD over the placebo-controlled treatment period.	Baseline up to EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)
Secondary	Change from baseline in Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score in former smokers	The E-RS: COPD is administered as a part of the 14-item EXACT questionnaire and is completed on a daily basis.The 11-item E-RS:COPD assesses severity of respiratory symptoms overall and severity of individual symptoms such as breathlessness, cough and sputum, and chest symptoms The total score of E-RS:COPD ranges from 0 to 40, with higher values indicating more severe respiratory symptoms.	Baseline to Week 24 and Week 52
Secondary	Rate of change in post-BD FEV1 (L) from baseline (post-BD FEV1 slope) in former smokers		Baseline up to EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)
Secondary	Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score in former smokers	The SGRQ is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. A global score ranges from 0 to 100. Scores by dimension are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A lower score indicates better quality of life.	Baseline to Week 24 and Week 52
Secondary	Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score in former smokers	The SGRQ is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. A global score ranges from 0 to 100. Scores by dimension are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A lower score indicates better quality of life.	Baseline to Week 24 and Week 52
Secondary	Incidence of treatment-emergent adverse events (TEAEs), adverse event of special interests (AESIs), serious adverse events (SAEs), and adverse events (AEs) leading to permanent treatment discontinuation in former smokers		Baseline up to End-of-Study (EOS) (Up to Week 72 for participants not transitioning to the extension study LTS18133; Up to Week 52 for participants transitioning to the extension study LTS18133)
Secondary	Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities in former smokers		Baseline up to EOS (Up to Week 72 for participants not transitioning to the extension study LTS18133; Up to Week 52 for participants transitioning to the extension study LTS18133)
Secondary	Functional itepekimab concentrations in serum in former smokers		Baseline up to EOS (Up to Week 72 for participants not transitioning to the extension study LTS18133; Up to Week 52 for participants transitioning to the extension study LTS18133)
Secondary	Incidence of treatment-emergent anti-itepekimab antibodies responses in former smokers		Baseline up to EOS (Up to Week 72 for participants not transitioning to the extension study LTS18133; Up to Week 52 for participants transitioning to the extension study LTS18133)
Secondary	Annualized rate of moderate or severe AECOPD in current smokers	Annualized rate of moderate or severe AECOPD over the placebo-controlled treatment period.	Baseline up to Week 52
Secondary	Change from baseline in pre-BD FEV1 in current smokers	FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.	Baseline up to Week 24 and Week 52
Secondary	Incidence of TEAEs, AESIs, SAEs, and AEs leading to permanent treatment discontinuation in current smokers		Baseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133)
Secondary	Incidence of potentially clinically significant laboratory, vital signs, and ECGs abnormalities in current smokers		Baseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133)
Secondary	Functional itepekimab concentrations in serum in current smokers		Baseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133)
Secondary	Incidence of treatment-emergent anti-itepekimab antibodies responses in current smokers		Baseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133)

External Links

•   EFC16819 COPD website