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

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— TITANIA  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05158387
• Other study ID #: D9180C00004
• Secondary ID: 2021-003771-34
• Status: Recruiting
• Phase: Phase 3
• Start date: February 7, 2022
• Est. completion date: August 28, 2025

Study information

• Verified date: March 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 28, 2025
• Est. primary completion date: June 5, 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
Australia	Research Site	Adelaide
Australia	Research Site	Campbelltown
Australia	Research Site	Frankstown
Australia	Research Site	Macquarie University
Australia	Research Site	Melbourne
Australia	Research Site	Nedlands
Australia	Research Site	Southport
Australia	Research Site	Spearwood
Australia	Research Site	Wollongong
Australia	Research Site	Woodville South
Brazil	Research Site	Blumenau
Brazil	Research Site	Botucatu
Brazil	Research Site	Brasilia
Brazil	Research Site	Curitiba
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Bernardo do Campo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Chile	Research Site	Curico
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Talca
China	Research Site	Anhui
China	Research Site	Baotou
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changde
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	Haikou
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Hohhot
China	Research Site	Kunming
China	Research Site	Linhai
China	Research Site	Nanchang
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Ningbo
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shengyang
China	Research Site	Shenyang
China	Research Site	Shenzhen
China	Research Site	Shenzhen
China	Research Site	Shijiazhuang
China	Research Site	Suzhou
China	Research Site	Suzhou
China	Research Site	Taiyuan
China	Research Site	Tianjin
China	Research Site	Urumqi
China	Research Site	Wuhan
China	Research Site	Wuxi
China	Research Site	Xiamen
China	Research Site	Xuzhou
China	Research Site	Xuzhou
China	Research Site	Yangzhou
China	Research Site	Yinchuan
China	Research Site	Yinchuan
China	Research Site	Zhanjiang
China	Research Site	Zunyi
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogotá
Colombia	Research Site	Ibague
Colombia	Research Site	Medellin
Colombia	Research Site	Rionegro
Colombia	Research Site	Zipaquira
France	Research Site	Brest Cedex 2
France	Research Site	Dijon Cedex
France	Research Site	Grenoble cedex 9
France	Research Site	Limoges
France	Research Site	Lyon Cedex
France	Research Site	Marseille
France	Research Site	Montivilliers
France	Research Site	Montpellier
France	Research Site	Pessac
France	Research Site	Saint-Herblain
France	Research Site	Suresnes Cedex
France	Research Site	Toulouse
Germany	Research Site	Bamberg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Darmstadt
Germany	Research Site	Frankfurt
Germany	Research Site	Großhansdorf
Germany	Research Site	Halle
Germany	Research Site	Köln
Germany	Research Site	Marburg
Germany	Research Site	München
Germany	Research Site	München-Pasing
Germany	Research Site	Peine
Greece	Research Site	Alexandroupolis
Greece	Research Site	Athens
Greece	Research Site	Exohi Thessaloniki
Greece	Research Site	Ioannina
Greece	Research Site	Patras
Greece	Research Site	Thessaloniki
Israel	Research Site	Ashkelon
Israel	Research Site	Beer Sheva
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar-Saba
Israel	Research Site	Rehovot
Israel	Research Site	Tel Aviv
Italy	Research Site	Bari
Italy	Research Site	Macerata
Italy	Research Site	Massa
Italy	Research Site	Messina
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Roma
Italy	Research Site	Salerno
Italy	Research Site	San Donà di Piave
Italy	Research Site	Sassari
Italy	Research Site	Statte
Italy	Research Site	Telese Terme
Italy	Research Site	Tradate
Italy	Research Site	Vercelli
Italy	Research Site	Verona
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Piura
Philippines	Research Site	Baguio
Philippines	Research Site	Cebu City
Philippines	Research Site	Iloilo City
Philippines	Research Site	Manila
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Bychawa
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Grodzisk Mazowiecki
Poland	Research Site	Grudziadz
Poland	Research Site	Katowice
Poland	Research Site	Krakow
Poland	Research Site	Kraków
Poland	Research Site	Lublin
Poland	Research Site	Nowa Sól
Poland	Research Site	Ostróda
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Rzeszów
Poland	Research Site	Skierniewice
Poland	Research Site	Sosnowiec
Poland	Research Site	Warszawa
Poland	Research Site	Wolomin
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Puerto Rico	Research Site	Caguas
Puerto Rico	Research Site	Ponce
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Bucharest
Romania	Research Site	Bucuresti
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Constanta
Romania	Research Site	Iasi
Romania	Research Site	Timisoara
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	Tomsk
Russian Federation	Research Site	Ulyanovsk
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
Taiwan	Research Site	Yunlin
Thailand	Research Site	Bang Kra So
Thailand	Research Site	Bangkok
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Muang
Thailand	Research Site	Muang,
Thailand	Research Site	Mueang
Thailand	Research Site	Nakhon Ratchasima
United Kingdom	Research Site	Blackpool
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Corby
United Kingdom	Research Site	Corby
United Kingdom	Research Site	Enfield
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Hampshire
United Kingdom	Research Site	High Wycombe
United Kingdom	Research Site	London
United Kingdom	Research Site	Northwood
United Kingdom	Research Site	Preston
United Kingdom	Research Site	Shipley
United Kingdom	Research Site	Wokingham
United States	Research Site	Amarillo	Texas
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Bay Pines	Florida
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Boerne	Texas
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bowling Green	Kentucky
United States	Research Site	Bronx	New York
United States	Research Site	Buffalo	New York
United States	Research Site	Cape Coral	Florida
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Cudahy	Wisconsin
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fullerton	California
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Greenwood	Indiana
United States	Research Site	Hannibal	Missouri
United States	Research Site	Lincoln	California
United States	Research Site	Macon	Georgia
United States	Research Site	McKinney	Texas
United States	Research Site	New Orleans	Louisiana
United States	Research Site	Newark	Delaware
United States	Research Site	Newport Beach	California
United States	Research Site	North Dartmouth	Massachusetts
United States	Research Site	Northridge	California
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Pensacola	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Richmond	Virginia
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	San Diego	California
United States	Research Site	Sheffield	Alabama
United States	Research Site	Tampa	Florida
United States	Research Site	Toledo	Ohio
United States	Research Site	Tomball	Texas
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Webster	Texas
United States	Research Site	West Valley City	Utah
United States	Research Site	White Marsh	Maryland
United States	Research Site	Williamsburg	Virginia
United States	Research Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Chile,  China,  Colombia,  France,  Germany,  Greece,  Israel,  Italy,  Peru,  Philippines,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Taiwan,  Thailand,  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]) 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