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

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— OBERON  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05166889
• Other study ID #: D9180C00003
• Secondary ID: 2021-003797-30
• Status: Recruiting
• Phase: Phase 3
• Start date: January 3, 2022
• Est. completion date: August 27, 2025

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 Dose 1 and Dose 2 administered subcutaneously (SC) in adult participants with symptomatic COPD and history of ≥ 2 moderate or ≥ 1 severe exacerbation of COPD in the previous 12 months. Participants should be receiving optimised treatment with maintenance inhaled therapy (ICS/LABA/LAMA triple therapy, or dual therapy if triple is not considered appropriate) in stable doses throughout at least 3 months prior to enrolment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1060
• Est. completion date: August 27, 2025
• Est. primary completion date: June 4, 2025
• 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 optimized inhaled dual or triple therapy at a stable dose 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.

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

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

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

14. 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.

15. Participants who have evidence of active TB.

16. Participants that have previously received tozorakimab.

17. 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.

18. Active vaping of any products or using smoked marijuana within the 6 months prior to randomization and during the study.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Tozorakimab
Administered subcutaneously tozorakimab Dose 1 and placebo through Week 52.
• Tozorakimab
Administered subcutaneously tozorakimab Dose 2 through Week 52.
• Placebo
Placebo administered subcutaneously, equivalent volume to tozorakimab through week 52.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
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	Ranelagh
Argentina	Research Site	San Fernando
Argentina	Research Site	San Miguel de Tucuman
Belgium	Research Site	Bruxelles
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Belgium	Research Site	Liege
Belgium	Research Site	Namur
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Haskovo
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Lovech
Bulgaria	Research Site	Petrich
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sandanski
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Troyan
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Vratsa
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Barrie	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Guelph	Ontario
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Kamloops	British Columbia
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Markham	Ontario
Canada	Research Site	Montreal	PQ
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Sherwood Park	Alberta
Canada	Research Site	Stouffville	Ontario
Canada	Research Site	Terrebonne	Quebec
Canada	Research Site	Winchester	Ontario
Czechia	Research Site	Brno
Czechia	Research Site	Broumov
Czechia	Research Site	Jihlava
Czechia	Research Site	Jindrichuv Hradec
Czechia	Research Site	Liberec 1
Czechia	Research Site	Mlada Boleslav
Czechia	Research Site	Olomouc
Czechia	Research Site	Rokycany
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
Finland	Research Site	Hämeenlinna
Finland	Research Site	Helsinki
Finland	Research Site	Kuopio
Finland	Research Site	Tampere
Finland	Research Site	Turku
Finland	Research Site	Turku
Hungary	Research Site	Baja
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Edelény
Hungary	Research Site	Encs
Hungary	Research Site	Gyöngyös
Hungary	Research Site	Mosonmagyaróvár
Hungary	Research Site	Százhalombatta
Hungary	Research Site	Székesfehérvár
India	Research Site	Ahmedabad
India	Research Site	Aligarh
India	Research Site	Belagavi
India	Research Site	Coimbatore
India	Research Site	Dehradun
India	Research Site	Hyderabad
India	Research Site	Jaipur
India	Research Site	Kolkatta
India	Research Site	Mohali
India	Research Site	Nagpur
India	Research Site	Nashik
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	Thane
Japan	Research Site	Asahikawa-shi
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chikushino-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Fujieda-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Iizuka-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Iwata-shi
Japan	Research Site	Izumi-shi
Japan	Research Site	Joyo-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kakogawa-shi
Japan	Research Site	Kamogawa-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kawachinagano-shi
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Kitakyusyu
Japan	Research Site	Kitakyusyu-shi
Japan	Research Site	Kiyose-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Kofu-shi
Japan	Research Site	Koga-shi
Japan	Research Site	Kokubunji-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Matsusaka-shi
Japan	Research Site	Meguro-ku
Japan	Research Site	Mitaka-shi
Japan	Research Site	Miyazaki-shi
Japan	Research Site	Mizunami-shi
Japan	Research Site	Nagaoka-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Narita-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Nishinomiya-shi
Japan	Research Site	Obihiro
Japan	Research Site	Okayama
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sakaide-shi
Japan	Research Site	Saku-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-Shi
Japan	Research Site	Seto-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Shizuoka-shi
Japan	Research Site	Tachikawa-shi
Japan	Research Site	Takamatsu-shi
Japan	Research Site	Toshima-ku
Japan	Research Site	Toyama-shi
Japan	Research Site	Toyonaka-shi
Japan	Research Site	Wakayama-shi
Japan	Research Site	Yamagata-shi
Japan	Research Site	Yanagawa-shi
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	Incheon
Korea, Republic of	Research Site	Jeonju-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Benito Juarez
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mérida
Mexico	Research Site	Mexico City
Mexico	Research Site	Monterrey
Mexico	Research Site	Morelia
Mexico	Research Site	Oaxaca
Mexico	Research Site	Veracruz
Netherlands	Research Site	Alkmaar
Netherlands	Research Site	Eindhoven
Netherlands	Research Site	Groningen
Netherlands	Research Site	Harderwijk
Netherlands	Research Site	Heerlen
Netherlands	Research Site	Zutphen
Netherlands	Research Site	Zwolle
Norway	Research Site	Ålesund
Norway	Research Site	Bergen
Norway	Research Site	Bodø
Norway	Research Site	Levanger
Norway	Research Site	Lørenskog
Norway	Research Site	Oslo
Norway	Research Site	Tønsberg
Portugal	Research Site	Guimaraes
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Matosinhos
Portugal	Research Site	Vila Franca de Xira
Portugal	Research Site	Vila Nova de Gaia
Puerto Rico	Research Site	Guaynabo
Puerto Rico	Research Site	San Juan
Spain	Research Site	Galdakao
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Merida
Spain	Research Site	Pozuelo de Alarcon
Spain	Research Site	Santander
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Sweden	Research Site	Göteborg
Sweden	Research Site	Göteborg
Sweden	Research Site	Lund
Sweden	Research Site	Malmö
Sweden	Research Site	Örebro
Sweden	Research Site	Stockholm
Turkey	Research Site	Ankara
Turkey	Research Site	Aydin
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Izmir
Turkey	Research Site	Mersin
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Bakersfield	California
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Boynton Beach	Florida
United States	Research Site	Brick	New Jersey
United States	Research Site	Bronx	New York
United States	Research Site	Brookhaven	Georgia
United States	Research Site	Buffalo	New York
United States	Research Site	Burlington	Vermont
United States	Research Site	Charleston	West Virginia
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	DuBois	Pennsylvania
United States	Research Site	Durham	North Carolina
United States	Research Site	Evanston	Illinois
United States	Research Site	Evergreen Park	Illinois
United States	Research Site	Fargo	North Dakota
United States	Research Site	Fort Worth	Texas
United States	Research Site	Franklin	Tennessee
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Guttenberg	New Jersey
United States	Research Site	Hawthorne	New York
United States	Research Site	Hershey	Pennsylvania
United States	Research Site	Houston	Texas
United States	Research Site	Huntsville	Alabama
United States	Research Site	Iowa City	Iowa
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kansas City	Kansas
United States	Research Site	Kingwood	Texas
United States	Research Site	Kissimmee	Florida
United States	Research Site	Marshfield	Wisconsin
United States	Research Site	Meridian	Idaho
United States	Research Site	Missoula	Montana
United States	Research Site	Mobile	Alabama
United States	Research Site	Montgomery	Alabama
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Hyde Park	New York
United States	Research Site	New York	New York
United States	Research Site	Normal	Illinois
United States	Research Site	North Massapequa	New York
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Palm Springs	California
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Plantation	Florida
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Rochester	Minnesota
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Sayre	Pennsylvania
United States	Research Site	Schenectady	New York
United States	Research Site	Sherman	Texas
United States	Research Site	Tacoma	Washington
United States	Research Site	Tempe	Arizona
United States	Research Site	Zachary	Louisiana
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  Finland,  Hungary,  India,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Portugal,  Puerto Rico,  Spain,  Sweden,  Turkey, 

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]) and then assessed in the overall population of participants.	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	Time to first moderate to severe COPD exacerbation in former smokers.	To explore the extent to which treatment with each dose of tozorakimab delays the time to first exacerbation compared with placebo in former smokers.	over 52 weeks
Secondary	Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in former smokers.	Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers.	Week 52, or over 52 weeks
Secondary	Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in the overall population of current and former smokers.	Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in the overall population of current and former smokers.	Week 52, or over 52 weeks
Secondary	Percentage of responders achieving MCID in E-RS:COPD total score in former smokers.	Responder analyses for E-RS:COPD total score at Week 52 based upon a = 2 point improvement (decrease) from baseline in former smokers.	Week 52
Secondary	Percentage of responders achieving MCID in E-RS:COPD total score in the overall population of current and former smokers.	Responder analyses for E-RS:COPD total score at Week 52 based upon a = 2 point improvement (decrease) from baseline in the overall population of current and former smokers.	Week 52
Secondary	Mean 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	Mean change from baseline in E-RS:COPD total score in the overall population of current and former 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	Percentage of responders achieving MCID in SGRQ total score in former smokers.	Percentage of participants with a decrease in SGRQ total score of = 4 points from baseline in former smokers.	Week 52
Secondary	Percentage of responders achieving MCID in SGRQ total score in the overall population of current and former smokers.	Percentage of participants with a decrease in SGRQ total score of = 4 points from baseline in the overall population of current and former smokers.	Week 52
Secondary	Mean 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	Mean 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	Time to first severe COPD exacerbation in former smokers.	To evaluate hazard ratio of first severe COPD exacerbation in 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.	over 52 weeks
Secondary	Change from baseline in CAT total score.	Analyses of change from baseline in CAT total score in former smokers.	Week 52
Secondary	Percentage of participants with a decrease in CAT total score in former smokers.	Proportion of participants achieving MCID in CAT total score, a decrease in CAT total score of = 2 points from baseline in former smokers.	Week 52
Secondary	Proportion of participants having = 1 healthcare resource utilization type in former smokers.	Proportion of participants having = 1 healthcare resource utilization type in former smokers.	over 52 weeks
Secondary	Annualized rate of healthcare resource utilization in former smokers.	Annualized rate of healthcare resource utilization in former smokers.	over 52 weeks
Secondary	The change from baseline in mean number of puffs per day in rescue use in former smokers.	Difference in mean number of puffs per day from baseline.	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 60 weeks