Clinical trial NCT05166889: Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: Chronic Obstructive Pulmonary Disease
COPD
tozorakimab
exacerbations
ICS
LABA/LAMA
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-12-22
Enrollment: 1132
Sex: ALL
Minimum age (years): 40
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers.
timeFrame: over 52 weeks
Secondary outcomes:
measure: Annualized rate of moderate to severe COPD exacerbations in former or current smokers.
timeFrame: over 52 weeks
measure: Time to first moderate to severe COPD exacerbation in former smokers.
timeFrame: over 52 weeks
measure: Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in former smokers.
timeFrame: Week 52, or over 52 weeks
measure: Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in the overall population of current and former smokers.
timeFrame: Week 52, or over 52 weeks
measure: Percentage of responders achieving MCID in E-RS:COPD total score in former smokers.
timeFrame: Week 52
measure: Percentage of responders achieving MCID in E-RS:COPD total score in the overall population of current and former smokers.
timeFrame: Week 52
measure: Mean change from baseline in E-RS:COPD total score in former smokers.
timeFrame: over 52 weeks
measure: Mean change from baseline in E-RS:COPD total score in the overall population of current and former smokers.
timeFrame: over 52 weeks
measure: Percentage of responders achieving MCID in SGRQ total score in former smokers.
timeFrame: Week 52
measure: Percentage of responders achieving MCID in SGRQ total score in the overall population of current and former smokers.
timeFrame: Week 52
measure: Mean change from baseline in SGRQ total score from in former smokers.
timeFrame: over 52 weeks
measure: Mean change from baseline in SGRQ total score from in the overall population of current and former smokers
timeFrame: over 52 weeks
measure: Time to first severe COPD exacerbation in former smokers.
timeFrame: over 52 weeks
measure: Annualized rate of severe COPD exacerbations in former smokers.
timeFrame: over 52 weeks
measure: Change from baseline in CAT total score.
timeFrame: Week 52
measure: Percentage of participants with a decrease in CAT total score in former smokers.
timeFrame: Week 52
measure: Proportion of participants having ≥ 1 healthcare resource utilization type in former smokers.
timeFrame: over 52 weeks
measure: Annualized rate of healthcare resource utilization in former smokers.
timeFrame: over 52 weeks
measure: The change from baseline in mean number of puffs per day in rescue use in former smokers.
timeFrame: over 52 weeks
measure: Trough serum concentrations of tozorakimab.
timeFrame: over 52 weeks
measure: Presence of anti-drug antibodies.
timeFrame: over 60 weeks
Other outcomes:
Locations:
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city: Troyan
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city: Vratsa
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city: Calgary
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state: Alberta
city: Edmonton
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state: Alberta
city: Sherwood Park
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state: Alberta
city: Kamloops
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state: British Columbia
city: Kelowna
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state: British Columbia
city: Ajax
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state: Ontario
city: Guelph
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state: Ontario
city: Markham
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city: Stouffville
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state: Ontario
city: Winchester
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state: Ontario
city: Montreal
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state: PQ
city: Terrebonne
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state: Quebec
city: Quebec
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city: Quebec
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facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Broumov
country: Czechia
facility: Research Site
city: Jindrichuv Hradec
country: Czechia
facility: Research Site
city: Liberec 1
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Rokycany
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city: Hvidovre
country: Denmark
facility: Research Site
city: København NV
country: Denmark
facility: Research Site
city: Næstved
country: Denmark
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city: Roskilde
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city: Vejle
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city: Ålborg
country: Denmark
facility: Research Site
city: Helsinki
country: Finland
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city: Hämeenlinna
country: Finland
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city: Kuopio
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city: Tampere
country: Finland
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city: Turku
country: Finland
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city: Turku
country: Finland
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city: Budapest
country: Hungary
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city: Debrecen
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city: Edelény
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city: Encs
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city: Mosonmagyaróvár
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city: Nyíregyháza-Sóstóhegy
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city: Százhalombatta
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city: Ahmedabad
country: India
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city: Belagavi
country: India
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city: Coimbatore
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country: India
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city: Hyderabad
country: India
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city: Jaipur
country: India
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city: Mohali
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city: Nagpur
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city: Nashik
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city: New Delhi
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city: Surat
country: India
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city: Thane
country: India
facility: Research Site
city: Asahikawa-shi
country: Japan
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city: Chikushino-shi
country: Japan
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city: Chuo-ku
country: Japan
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city: Fujieda-shi
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city: Fukuoka-shi
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city: Hamamatsu-shi
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city: Hamamatsu-shi
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city: Hiroshima-shi
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city: Obihiro
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city: Okayama
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city: Osaka-shi
country: Japan
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city: Osaka-shi
country: Japan
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city: Osaka-shi
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
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city: Shinjuku-ku
country: Japan
facility: Research Site
city: Shizuoka-shi
country: Japan
facility: Research Site
city: Toshima-ku
country: Japan
facility: Research Site
city: Toyonaka-shi
country: Japan
facility: Research Site
city: Yanagawa-shi
country: Japan
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city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Jeonju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
facility: Research Site
city: Benito Juarez
country: Mexico
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city: Chihuahua
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city: Guadalajara
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
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city: Monterrey
country: Mexico
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city: Morelia
country: Mexico
facility: Research Site
city: Mérida
country: Mexico
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city: Oaxaca
country: Mexico
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city: Veracruz
country: Mexico
facility: Research Site
city: Alkmaar
country: Netherlands
facility: Research Site
city: Eindhoven
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Harderwijk
country: Netherlands
facility: Research Site
city: Heerlen
country: Netherlands
facility: Research Site
city: Zutphen
country: Netherlands
facility: Research Site
city: Zwolle
country: Netherlands
facility: Research Site
city: Bergen
country: Norway
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city: Bodø
country: Norway
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city: Levanger
country: Norway
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city: Lørenskog
country: Norway
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city: Oslo
country: Norway
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city: Tønsberg
country: Norway
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city: Ålesund
country: Norway
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city: Guimaraes
country: Portugal
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city: Lisboa
country: Portugal
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city: Lisboa
country: Portugal
facility: Research Site
city: Matosinhos
country: Portugal
facility: Research Site
city: Vila Franca de Xira
country: Portugal
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city: Vila Nova de Gaia
country: Portugal
facility: Research Site
city: Guaynabo
country: Puerto Rico
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city: Galdakao
country: Spain
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city: Madrid
country: Spain
facility: Research Site
city: Merida
country: Spain
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city: Málaga
country: Spain
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city: Pozuelo de Alarcon
country: Spain
facility: Research Site
city: Santander
country: Spain
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city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Göteborg
country: Sweden
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city: Göteborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Malmö
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Aydin
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Mersin
country: Turkey
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
References: