Clinical trial NCT05158387: 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 (TITANIA)
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: 2021-12-15
Enrollment: 1172
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:
city: Sheffield
country: United States
facility: Research Site
state: Alabama
city: Lincoln
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Northridge
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state: California
city: Colorado Springs
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city: Toledo
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city: Oklahoma City
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city: Sao Bernardo do Campo
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city: Santiago
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city: Santiago
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city: Santiago
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city: Santiago
country: Chile
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city: Talca
country: Chile
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city: Baotou
country: China
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country: China
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city: Beijing
country: China
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city: Changchun
country: China
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city: Changde
country: China
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country: China
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country: China
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country: China
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country: China
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city: Chongqing
country: China
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country: China
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country: China
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country: China
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country: China
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city: Haikou
country: China
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city: Hangzhou
country: China
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city: Hefei
country: China
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city: Hohhot
country: China
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city: Kunming
country: China
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city: Linhai
country: China
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city: Nanchang
country: China
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city: Nanjing
country: China
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city: Ningbo
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shengyang
country: China
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city: Shenyang
country: China
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city: Shenzhen
country: China
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city: Shenzhen
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Suzhou
country: China
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city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
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city: Wuhan
country: China
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city: Wuxi
country: China
facility: Research Site
city: Xiamen
country: China
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city: Xuzhou
country: China
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city: Xuzhou
country: China
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city: Yangzhou
country: China
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city: Yinchuan
country: China
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city: Zhanjiang
country: China
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city: Zunyi
country: China
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city: Barranquilla
country: Colombia
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city: Ibague
country: Colombia
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city: Rionegro
country: Colombia
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city: Zipaquira
country: Colombia
facility: Research Site
city: Brest Cedex 2
country: France
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city: Dijon
country: France
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city: Grenoble cedex 9
country: France
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city: Lyon Cedex
country: France
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country: France
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city: Montivilliers
country: France
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city: Montpellier
country: France
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country: France
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city: Saint-Herblain
country: France
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city: Toulouse
country: France
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city: Ahrensburg
country: Germany
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city: Bamberg
country: Germany
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city: Berlin
country: Germany
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city: Berlin
country: Germany
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city: Darmstadt
country: Germany
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city: Halle
country: Germany
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city: Köln
country: Germany
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city: Marburg
country: Germany
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city: München-Pasing
country: Germany
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city: München
country: Germany
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city: Peine
country: Germany
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city: Alexandroupolis
country: Greece
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city: Athens
country: Greece
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city: Exohi Thessaloniki
country: Greece
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city: Ioannina
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city: Patras
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city: Thessaloniki
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city: Milano
country: Italy
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city: Napoli
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city: Roma
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city: Salerno
country: Italy
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city: San Donà di Piave
country: Italy
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city: Sassari
country: Italy
facility: Research Site
city: Statte
country: Italy
facility: Research Site
city: Telese Terme
country: Italy
facility: Research Site
city: Tradate
country: Italy
facility: Research Site
city: Vercelli
country: Italy
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city: Verona
country: Italy
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Baguio
country: Philippines
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city: Cebu City
country: Philippines
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city: Iloilo City
country: Philippines
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city: Białystok
country: Poland
facility: Research Site
city: Białystok
country: Poland
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city: Bychawa
country: Poland
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city: Bydgoszcz
country: Poland
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city: Katowice
country: Poland
facility: Research Site
city: Krakow
country: Poland
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city: Lublin
country: Poland
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city: Ostrowiec Świętokrzyski
country: Poland
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city: Ostróda
country: Poland
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city: Poznań
country: Poland
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city: Poznań
country: Poland
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city: Rzeszów
country: Poland
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city: Skierniewice
country: Poland
facility: Research Site
city: Sosnowiec
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Ponce
country: Puerto Rico
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city: Brasov
country: Romania
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city: Bucharest
country: Romania
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city: Cluj-Napoca
country: Romania
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city: Constanta
country: Romania
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city: Timisoara
country: Romania
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city: Penza
country: Russian Federation
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city: Saratov
country: Russian Federation
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city: Hsinchu
country: Taiwan
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city: Kaohsiung
country: Taiwan
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city: Kaohsiung
country: Taiwan
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city: Taichung
country: Taiwan
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city: Taichung
country: Taiwan
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city: Taipei City
country: Taiwan
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city: Taipei
country: Taiwan
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city: Taoyuan
country: Taiwan
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city: Yunlin
country: Taiwan
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city: Bang Kra So
country: Thailand
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city: Bangkok
country: Thailand
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city: Hat Yai
country: Thailand
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city: Khon Kaen
country: Thailand
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city: Muang,
country: Thailand
facility: Research Site
city: Muang
country: Thailand
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city: Mueang
country: Thailand
facility: Research Site
city: Nakhon Ratchasima
country: Thailand
facility: Research Site
city: Bradford
country: United Kingdom
facility: Research Site
city: Corby
country: United Kingdom
facility: Research Site
city: Corby
country: United Kingdom
facility: Research Site
city: Enfield
country: United Kingdom
facility: Research Site
city: Hampshire
country: United Kingdom
facility: Research Site
city: High Wycombe
country: United Kingdom
facility: Research Site
city: Northwood
country: United Kingdom
facility: Research Site
city: Preston
country: United Kingdom
facility: Research Site
city: Shipley
country: United Kingdom
facility: Research Site
Study officials:
References: