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

NCT05158387
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Phase
Phase 3
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Recruitment status
Completed
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Participants
1,172
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Lead sponsor
AstraZeneca
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Start date
2022-02-07
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Number of sites
212
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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.
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Acronym
TITANIA
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Short title
Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations.
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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)
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 3
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Study type
Interventional
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Completion date
2026-03-22
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First posted
2021-12-15
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Registry last updated
2026-04-16
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Primary completion date
2026-01-19
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Start date
2022-02-07
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Actual participants
1,172
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Participants
1,172
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Participant count basis
Actual
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Protocol amendments
5
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Number of sites
212
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
AstraZeneca
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05158387
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ClinicalTrials.gov ID
NCT05158387
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Triple masking
Masking description
unblinded administrator/pharmacist
Masked roles
Participants, Care providers, Investigators
Sources for study design
clinicaltrials.gov

  1. Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers.

    Timeframe: over 52 weeks

    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.

  1. Annualized rate of moderate to severe COPD exacerbations in former or current smokers.

    Timeframe: over 52 weeks

    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.

  2. Time to first moderate to severe COPD exacerbation in former smokers.

    Timeframe: over 52 weeks

    To explore the extent to which treatment with each dose of tozorakimab delays the time to first exacerbation compared with placebo in former smokers.

  3. Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in former smokers.

    Timeframe: Week 52, or over 52 weeks

    Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers.

  4. 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

    Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in the overall population of current and former smokers.

  5. Percentage of responders achieving MCID in E-RS:COPD total score in former smokers

    Timeframe: Week 52

    Responder analyses for E-RS:COPD total score at Week 52 based upon a ≥ 2 point improvement (decrease) from baseline in former smokers.

  6. Percentage of responders achieving MCID in E-RS:COPD total score in the overall population of current and former smokers.

    Timeframe: Week 52

    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.

  7. Mean change from baseline in E-RS:COPD total score in former smokers.

    Timeframe: over 52 weeks

    Difference in mean change in E-RS:COPD total score from baseline in former smokers.

  8. Mean change from baseline in E-RS:COPD total score in the overall population of current and former smokers.

    Timeframe: over 52 weeks

    Difference in mean change in E-RS:COPD total score from baseline in the overall population of current and former smokers.

  9. Percentage of responders achieving MCID in SGRQ total score in former smokers.

    Timeframe: Week 52

    Percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline in former smokers.

  10. Percentage of responders achieving MCID in SGRQ total score in the overall population of current and former smokers.

    Timeframe: Week 52

    Percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline in the overall population of current and former smokers.

  11. Mean change from baseline in SGRQ total score from in former smokers.

    Timeframe: over 52 weeks

    Difference in mean change from baseline in SGRQ total score in former smokers.

  12. Mean change from baseline in SGRQ total score from in the overall population of current and former smokers.

    Timeframe: over 52 weeks

    Difference in mean change from baseline in SGRQ total score in the overall population of current and former smokers.

  13. Time to first severe COPD exacerbation in former smokers.

    Timeframe: over 52 weeks

    To evaluate hazard ratio of first severe COPD exacerbation in former smokers.

  14. Annualized rate of severe COPD exacerbations in former smokers.

    Timeframe: over 52 weeks

    The rate ratio of severe COPD exacerbations will be assessed in former smokers.

  15. Change from baseline in CAT total score.

    Timeframe: Week 52

    Analyses of change from baseline in CAT total score in former smokers.

  16. Percentage of participants with a decrease in CAT total score in former smokers.

    Timeframe: Week 52

    Proportion of participants achieving MCID in CAT total score, a decrease in CAT total score of ≥ 2 points from baseline in former smokers.

  17. Proportion of participants having ≥ 1 healthcare resource utilization type in former smokers.

    Timeframe: over 52 weeks

    Proportion of participants having ≥ 1 healthcare resource utilization type in former smokers.

  18. Annualized rate of healthcare resource utilization in former smokers.

    Timeframe: over 52 weeks

    Annualized rate of healthcare resource utilization in former smokers.

  19. The change from baseline in mean number of puffs per day in rescue use in former smokers.

    Timeframe: over 52 weeks

    Difference in mean number of puffs per day from baseline.

  20. Trough serum concentrations of tozorakimab.

    Timeframe: over 52 weeks

    Pharmacokinetics: concentrations of tozorakimab in trough serum.

  21. Presence of anti-drug antibodies.

    Timeframe: over 60 weeks

    Immunogenicity: presence of tozorakimab anti-drug antibodies in blood serum.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
40 Years
Maximum age
130 Years
Healthy volunteers
No

  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

  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.
Sources for eligibility
clinicaltrials.gov

  • Research SiteSheffield, United States
  • Research SiteLincoln, United States
  • Research SiteNewport Beach, United States
  • Research SiteNorthridge, United States
  • Research SiteColorado Springs, United States
  • Research SiteNewark, United States
  • Research SiteBay Pines, United States
  • Research SiteCape Coral, United States
  • Research SitePensacola, United States
  • Research SiteTampa, United States
  • Research SiteWinter Park, United States
  • Research SiteMacon, United States
  • Research SiteGreenwood, United States
  • Research SiteBowling Green, United States
  • Research SiteWhite Marsh, United States
  • Research SiteNorth Dartmouth, United States
  • Research SiteAnn Arbor, United States
  • Research SiteFarmington Hills, United States
  • Research SiteGrand Rapids, United States
  • Research SiteBuffalo, United States
  • Research SiteThe Bronx, United States
  • Research SiteToledo, United States
  • Research SiteOklahoma City, United States
  • Research SiteTulsa, United States
  • Research SitePhiladelphia, United States

And 187 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2021-003771-34
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (2)