Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— MIRANDA  

Official title:

A Phase III, Multicentre, Randomised, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Tozorakimab in Participants With Symptomatic Chronic Obstructive Pulmonary Disease (COPD) With a History of COPD Exacerbations (MIRANDA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06040086
• Other study ID #: D9180C00012
• Secondary ID: 2023-505543-39
• Status: Recruiting
• Phase: Phase 3
• Start date: September 22, 2023
• Est. completion date: December 7, 2026

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this Phase III study is to evaluate the efficacy and safety of tozorakimab administered subcutaneously (SC) in adult participants with symptomatic COPD with a history of ≥ 2 moderate or ≥ 1 severe exacerbations of COPD in the 12 months prior to enrolment. Participants should be receiving optimised treatment with inhaled maintenance therapy (ICS/LABA/LAMA triple therapy, or dual therapy if triple is not considered appropriate) throughout at least the last 3 months prior to enrolment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1240
• Est. completion date: December 7, 2026
• Est. primary completion date: September 10, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Participant must be = 40 years of age and capable of giving signed informed consent.

2. Documented diagnosis of COPD for at least one year prior to enrolment.

3. Post BD FEV1/FVC < 0.70 and post-BD FEV1 >20% of predicted normal value

4. Documented history of = 2 moderate or = 1 severe COPD exacerbations within 12 months prior to enrolment.

5. Documented optimised inhaled dual or triple therapy for at least 3 months prior to enrolment.

6. Smoking history of = 10 pack-years.

7. CAT total score = 10, with each of the phlegm (sputum) and cough items with a score = 2

Exclusion Criteria:

1. Clinically important pulmonary disease other than COPD.

2. Radiological findings suggestive of a respiratory disease other than COPD that is significantly contributing to the participant's respiratory symptoms. Radiological findings of pulmonary nodules suspicious for lung cancer, as per applicable guidances, without appropriate follow up prior to randomisation. Radiological findings suggestive of acute infection.

3. Current diagnosis of asthma, prior history of asthma, or asthma-COPD overlap. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of 18

4. Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that could affect safety, study findings or participants ability to complete the study.

5. COPD exacerbation, within 2 weeks prior to randomization, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalization.

6. Active significant infection within the 4 weeks prior to randomization, pneumonia within 6 weeks prior to randomization, or medical condition that predisposes the participant to infection.

7. Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.

8. Significant COVID-19 illness within the 6 months prior to enrolment.

9. Unstable cardiovascular disorder.

10. Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure.

11. History of active severe inflammatory bowel disease or colitis within one year prior to enrolment, or unexplained diarrhoea within the 4 weeks prior to randomisation.

12. History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV 2.

13. History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C)

14. Evidence of active liver disease, including jaundice during screening.

15. Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than one year prior to enrolment. Suspected malignancy or undefined neoplasms.

16. Participants who have evidence of active TB.

17. History of partial or total lung resection.

18. Scheduled major surgical procedure during the course of the study.

19. Participants that have previously received tozorakimab.

20. Any clinically significant abnormal findings in physical examination, vital signs, ECG, or laboratory testing during the screening period, which in the opinion of the investigator may put the participant at risk because of their participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Placebo
Placebo administered subcutaneously, equivalent volume to tozorakimab throughout the study.
• Tozorakimab
Administered subcutaneously tozorakimab and placebo throughout the study.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Córdoba
Argentina	Research Site	Florencio Varela
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Mendoza
Argentina	Research Site	Quilmes
Argentina	Research Site	San Fernando
Argentina	Research Site	San Miguel de Tucuman
Belgium	Research Site	Brussels
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Kortrijk
Belgium	Research Site	Leuven
Belgium	Research Site	Liege
Belgium	Research Site	Mechelen
Belgium	Research Site	Namur
Belgium	Research Site	Roeselare
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Blumenau
Brazil	Research Site	Campina Grande do Sul
Brazil	Research Site	Campinas
Brazil	Research Site	Campinas
Brazil	Research Site	Fortaleza
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Sao Bernardo do Campo
Brazil	Research Site	Sao Jose Do Rio Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Valinhos
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Haskovo
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Panagyurishte
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Veliko Tanovo
Bulgaria	Research Site	Yambol
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	St Charles Borromee	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Winchester	Ontario
Chile	Research Site	Concepción
Chile	Research Site	Curico
Chile	Research Site	Quillota
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Viña del Mar
China	Research Site	Anhui
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hohhot
China	Research Site	Huizhou
China	Research Site	Jieyang
China	Research Site	Jinan
China	Research Site	Lanzhou
China	Research Site	Liaocheng
China	Research Site	Linhai
China	Research Site	Nan Chong
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Nantong
China	Research Site	Ningbo
China	Research Site	Pingxiang
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenyang
China	Research Site	Shenzhen
China	Research Site	ShiJiazhuang
China	Research Site	Shijiazhuang
China	Research Site	Taizhou
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Xuzhou
China	Research Site	Xuzhou
China	Research Site	Yinchuan
China	Research Site	Zigong
Denmark	Research Site	Aarhus
Denmark	Research Site	Ålborg
Denmark	Research Site	Hvidovre
Denmark	Research Site	København NV
Denmark	Research Site	Næstved
Denmark	Research Site	Roskilde
Denmark	Research Site	Vejle
France	Research Site	Aix en Provence
France	Research Site	Brest Cedex
France	Research Site	Colmar
France	Research Site	Epagny Metz-Tessy
France	Research Site	La Tronche
France	Research Site	Libourne Cedex
France	Research Site	Lyon Cedex 04
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Quimper cedex
France	Research Site	Reims
France	Research Site	Strasbourg Cedex
France	Research Site	Villefranche Sur Saone
Germany	Research Site	Augsburg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Darmstadt
Germany	Research Site	Essen
Germany	Research Site	Frankfurt
Germany	Research Site	Frankfurt/Main
Germany	Research Site	Großhansdorf
Germany	Research Site	Halle
Germany	Research Site	Halle (Saale)
Germany	Research Site	Hannover
Germany	Research Site	Köln
Germany	Research Site	Leipzig
Germany	Research Site	Marburg
Germany	Research Site	Moers
Germany	Research Site	München
Germany	Research Site	München-Pasing
Germany	Research Site	Nürnberg
Germany	Research Site	Peine
Germany	Research Site	Solingen
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Exohi Thessaloniki
Greece	Research Site	Heraklion
Greece	Research Site	Ioannina
Greece	Research Site	Thessaloniki
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Edelény
Hungary	Research Site	Encs
Hungary	Research Site	Gödöllo
Hungary	Research Site	Hajdúnánás
Hungary	Research Site	Mosonmagyaróvár
Hungary	Research Site	Pécs
Hungary	Research Site	Püspökladány
Hungary	Research Site	Százhalombatta
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Szolnok
India	Research Site	Ajmer
India	Research Site	Coimbatore
India	Research Site	Dehradun
India	Research Site	Delhi
India	Research Site	Dwarka
India	Research Site	Hyderabad
India	Research Site	Jaipur
India	Research Site	Jaipur
India	Research Site	Nagpur
India	Research Site	Thane
India	Research Site	Vijayawada
India	Research Site	Visakhapatnam
Ireland	Research Site	Cork
Ireland	Research Site	Dublin
Ireland	Research Site	Dublin
Ireland	Research Site	Galway
Italy	Research Site	Cona
Italy	Research Site	Foggia
Italy	Research Site	Modena
Italy	Research Site	Napoli
Italy	Research Site	Padua
Italy	Research Site	Pavia
Italy	Research Site	Pisa
Italy	Research Site	Roma
Japan	Research Site	Aomori-shi
Japan	Research Site	Asahikawa-shi
Japan	Research Site	Chikushino-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fujieda-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Ginowan-shi
Japan	Research Site	Hakodate-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Iizuka-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Izumi-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kasuga-shi
Japan	Research Site	Kasugai-shi
Japan	Research Site	Kawachinagano-shi
Japan	Research Site	Kitakyushu-shi
Japan	Research Site	Kiyose-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Kusatsu-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Matsusaka-shi
Japan	Research Site	Mino-shi
Japan	Research Site	Minokamo shi
Japan	Research Site	Mizunami-shi
Japan	Research Site	Morioka-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nankoku-shi
Japan	Research Site	Nankoku-shi
Japan	Research Site	Ogaki-shi
Japan	Research Site	Okinawa-shi
Japan	Research Site	Omuta-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sakaide-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Shizuoka-shi
Japan	Research Site	Tachikawa-shi
Japan	Research Site	Toon-shi
Japan	Research Site	Toride-shi
Japan	Research Site	Toshima-ku
Japan	Research Site	Toyonaka-shi
Japan	Research Site	Ube
Japan	Research Site	Ueda-shi
Japan	Research Site	Urasoe-shi
Japan	Research Site	Urayasu-shi
Japan	Research Site	Utsunomiya-shi
Japan	Research Site	Yanagawa-shi
Japan	Research Site	Yokohama
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Jeonju
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Malaysia	Research Site	Kajang
Malaysia	Research Site	Kota Bharu
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuantan
Malaysia	Research Site	Sarawak Miri
Malaysia	Research Site	Seremban
Mexico	Research Site	Benito Juarez
Mexico	Research Site	Chihuahua
Mexico	Research Site	Culiacan
Mexico	Research Site	Durango
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico City
Mexico	Research Site	Monterrey
Mexico	Research Site	Monterrey
Mexico	Research Site	Oaxaca
Mexico	Research Site	Queretaro
Mexico	Research Site	Tijuna
Mexico	Research Site	Veracruz
Netherlands	Research Site	Arnhem
Netherlands	Research Site	Breda
Netherlands	Research Site	Den Bosch
Netherlands	Research Site	Groningen
Netherlands	Research Site	Harderwijk
Netherlands	Research Site	Heerlen
Netherlands	Research Site	Roermond
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Zutphen
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Piura
Peru	Research Site	Santa Beatriz
Poland	Research Site	Bialystok
Poland	Research Site	Bielsko-Biala
Poland	Research Site	Bydgoszcz
Poland	Research Site	Chrzanów
Poland	Research Site	Grodzisk Mazowiecki
Poland	Research Site	Katowice
Poland	Research Site	Kielce
Poland	Research Site	Krakow
Poland	Research Site	Kraków
Poland	Research Site	Kraków
Poland	Research Site	Lublin
Poland	Research Site	Ostróda
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Plock
Poland	Research Site	Poznan
Poland	Research Site	Rzeszów
Poland	Research Site	Slupsk
Poland	Research Site	Sosnowiec
Spain	Research Site	Badalona(Barcelona)
Spain	Research Site	Barcelona
Spain	Research Site	Caceres
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Mérida
Spain	Research Site	Santander
Spain	Research Site	Zaragoza
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khlong Luang
Thailand	Research Site	Muang
Thailand	Research Site	Muang
Thailand	Research Site	Mueang
Thailand	Research Site	Nakhon Ratchasima
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Mersin
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Corby
United Kingdom	Research Site	Cottingham
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Macclesfield
United Kingdom	Research Site	Newcastle upon Tyne
United Kingdom	Research Site	Portsmouth
United Kingdom	Research Site	Wakefield
United States	Research Site	Andover	Kansas
United States	Research Site	Aurora	Colorado
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bowling Green	Kentucky
United States	Research Site	Boynton Beach	Florida
United States	Research Site	Bronx	New York
United States	Research Site	Canton	Michigan
United States	Research Site	Champaign	Illinois
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chesterfield	Missouri
United States	Research Site	Chesterfield	Missouri
United States	Research Site	Chicago	Illinois
United States	Research Site	Columbus	Georgia
United States	Research Site	Cortland	New York
United States	Research Site	Dayton	Ohio
United States	Research Site	Decatur	Alabama
United States	Research Site	Denver	Colorado
United States	Research Site	East Providence	Rhode Island
United States	Research Site	El Paso	Texas
United States	Research Site	Elizabethton	Tennessee
United States	Research Site	Fort Wayne	Indiana
United States	Research Site	Gaffney	South Carolina
United States	Research Site	Grants Pass	Oregon
United States	Research Site	Greenville	North Carolina
United States	Research Site	Hannibal	Missouri
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Huntersville	North Carolina
United States	Research Site	Jackson	Tennessee
United States	Research Site	Kenosha	Wisconsin
United States	Research Site	Lakeland	Florida
United States	Research Site	Lakeland	Florida
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lexington	Kentucky
United States	Research Site	McKinney	Texas
United States	Research Site	McKinney	Texas
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	New Orleans	Louisiana
United States	Research Site	Newport Beach	California
United States	Research Site	Ocala	Florida
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orange	California
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Peoria	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Roy	Utah
United States	Research Site	Rutland	Vermont
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Francisco	California
United States	Research Site	Sheffield	Alabama
United States	Research Site	Toms River	New Jersey
United States	Research Site	Towson	Maryland
United States	Research Site	Tucson	Arizona
United States	Research Site	Tucson	Arizona
United States	Research Site	Union	South Carolina
United States	Research Site	Washington	District of Columbia
United States	Research Site	Winfield	Illinois
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Wooster	Ohio
United States	Research Site	Yuma	Arizona
Vietnam	Research Site	Ha Noi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh City
Vietnam	Research Site	Hochiminh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Denmark,  France,  Germany,  Greece,  Hungary,  India,  Ireland,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Peru,  Poland,  Spain,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers.	The primary endpoint will be assessed first in the primary population (former smokers with symptomatic COPD and a history of exacerbations, on optimised treatment with maintenance inhaled therapy [triple therapy, or dual therapy if triple is not considered appropriate]).	Over 52 weeks
Secondary	Annualized rate of moderate to severe COPD exacerbations in former or current smokers.	The annualized rate will be assessed in the overall population of participants including current and former smokers with symptomatic COPD and history of exacerbations, on optimised treatment with maintenance inhaled therapy.	Over 52 weeks
Secondary	Change from baseline in SGRQ total score from in former smokers	Difference in mean change from baseline in SGRQ total score in former smokers.	Over 52 weeks
Secondary	Change from baseline in SGRQ total score from in the overall population of current and former smokers.	Difference in mean change from baseline in SGRQ total score in the overall population of current and former smokers.	Over 52 weeks
Secondary	Annualized rate of severe COPD exacerbations in former smokers	The rate ratio of severe COPD exacerbations will be assessed in former smokers.	Variable duration period up to study completion, maximum of approximately 3 years
Secondary	Annualized rate of severe COPD exacerbations in former or current smokers	The rate ratio of severe COPD exacerbations will be assessed in the overall population of current and former smokers.	Variable duration period up to study completion, maximum of approximately 3 years
Secondary	Change from baseline in E-RS:COPD total score in former smokers	Difference in mean change in E-RS:COPD total score from baseline in former smokers.	Over 52 weeks
Secondary	Change from baseline in E-RS:COPD total score in former or current smokers	Difference in mean change in E-RS:COPD total score from baseline in the overall population of current and former smokers.	Over 52 weeks
Secondary	Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers	Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers.	Week 52, over 52 weeks
Secondary	Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former or current smokers	Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in the overall population of current and former smokers.	Week 52, over 52 weeks
Secondary	Time to first moderate to severe COPD exacerbation	Time to first moderate to severe COPD exacerbation compared with placebo.	Over 52 weeks
Secondary	Time to first severe COPD exacerbation	Time to first severe COPD exacerbation compared with placebo.	Variable duration period up to study completion, maximum of approximately 3 years
Secondary	Change from baseline in CAT total score	Change from baseline in CAT total score compared with placebo.	Week 52
Secondary	Proportion of participants achieving MCID in CAT score	Proportion of participants achieving MCID in CAT score (percentage of participants with a decrease in CAT total score of = 2 points from baseline).	Week 52
Secondary	Proportion of participants achieving MCID in SGRQ total score	Proportion of participants achieving MCID in SGRQ score (percentage of participants with a decrease in SGRQ total score of = 4 points from baseline).	Week 52
Secondary	Proportion of participants achieving MCID in E-RS:COPD total score	Proportion of participants achieving MCID in E-RS:COPD total score (percentage of participants with a decrease in E-RS:COPD total score of = 2 points from baseline).	Week 52
Secondary	Annualized rate of healthcare resource utilization	Annualized rate of healthcare resource utilization.	Variable duration period up to study completion, maximum of approximately 3 years
Secondary	Change from baseline in rescue medication	Change from baseline (difference in mean number of puffs/day) in rescue medication use.	Over 52 weeks
Secondary	Trough serum concentrations of tozorakimab	Pharmacokinetics: concentrations of tozorakimab in trough serum.	Over 52 weeks
Secondary	Presence of anti-drug antibodies	Immunogenicity: presence of tozorakimab anti-drug antibodies in blood serum.	Over 52 weeks
Secondary	Time to death	Time to death (all-cause mortality)	Variable duration period up to study completion, maximum of approximately 3 years