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

NCT06040086
clinicaltrials.gov
Phase
Phase 3
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Recruitment status
Completed
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Participants
1,454
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Lead sponsor
AstraZeneca
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Start date
2023-09-22
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Number of sites
368
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Summary
The purpose of this Phase III study is to evaluate the efficacy and safety of tozorakimab administered subcutaneously (SC) in adult participants with symptomatic COPD with a history of ≥ 2 moderate or ≥ 1 severe exacerbations of COPD in the 12 months prior to enrolment. Participants should be receiving optimised treatment with inhaled maintenance therapy (ICS/LABA/LAMA triple therapy, or dual therapy if triple is not considered appropriate) throughout at least the last 3 months prior to enrolment.
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Acronym
MIRANDA
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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 Tozorakimab in Participants With Symptomatic Chronic Obstructive Pulmonary Disease (COPD) With a History of COPD Exacerbations (MIRANDA)
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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
2026-05-22
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First posted
2023-09-15
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Registry last updated
2026-07-24
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Primary completion date
2026-03-06
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Start date
2023-09-22
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Actual participants
1,454
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Participants
1,454
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Participant count basis
Actual
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Protocol amendments
3
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Number of sites
368
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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
NCT06040086
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ClinicalTrials.gov ID
NCT06040086
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
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 in the primary population (former smokers with symptomatic COPD and a history of exacerbations, on optimised treatment with maintenance inhaled therapy \[triple therapy, or dual therapy if triple is not considered appropriate\]).

  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. 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.

  3. 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.

  4. Annualized rate of severe COPD exacerbations in former smokers

    Timeframe: Variable duration period up to study completion, approximately 3 years

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

  5. Annualized rate of severe COPD exacerbations in former or current smokers

    Timeframe: Variable duration period up to study completion, approximately 3 years

    The rate ratio of severe COPD exacerbations will be assessed in the overall population of current and former smokers.

  6. 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.

  7. Change from baseline in E-RS:COPD total score in former or current 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.

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

    Timeframe: Over 52 weeks

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

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

    Timeframe: Over 52 weeks

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

  10. Change from baseline in post-bronchodilator FEV1 (mL) in former smokers

    Timeframe: Week 52

    Change from baseline in post-bronchodilator FEV1 (mL) in former smokers.

  11. Change from baseline in post-bronchodilator FEV1 (mL) in former smokers or current smokers

    Timeframe: Week 52

    Change from baseline in post-bronchodilator FEV1 (mL) in former smokers or current smokers.

  12. Annualised rate of COPD exacerbations requiring hospitalisations and/or Emergency Room (ER)/Emergency Department (ED) visits in former smokers

    Timeframe: Variable duration period up to study completion, approximately 3 years

    The rate ratio of COPD exacerbations requiring hospitalisations and/or Emergency Room (ER)/Emergency Department (ED) visits in former smokers.

  13. Annualised rate of COPD exacerbations requiring hospitalisations and/or Emergency Room (ER)/Emergency Department (ED) visits in former or current smokers

    Timeframe: Variable duration period up to study completion, approximately 3 years

    The rate ratio of COPD exacerbations requiring hospitalisations and/or Emergency Room (ER)/Emergency Department (ED) visits in former or current smokers.

  14. Change from baseline in pre-BD, pre-dose trough FEV1 (mL)

    Timeframe: 52 weeks

    Change from baseline in pre-BD, pre-dose trough FEV1 (mL).

  15. Change from baseline in post-BD FEV1 (mL)

    Timeframe: Over 52 weeks

    Change from baseline in post-BD FEV1 (mL).

  16. Time to first moderate to severe COPD exacerbation

    Timeframe: Over 52 weeks

    Time to first moderate to severe COPD exacerbation compared with placebo.

  17. Time to first severe COPD exacerbation

    Timeframe: Variable duration period up to study completion, approximately 3 years

    Time to first severe COPD exacerbation compared with placebo.

  18. Change from baseline in CAT total score

    Timeframe: Week 52

    Change from baseline in CAT total score compared with placebo.

  19. Proportion of participants achieving MCID in CAT score

    Timeframe: Week 52

    Proportion of participants achieving MCID in CAT score (percentage of participants with a decrease in CAT total score of ≥ 2 points from baseline).

  20. Proportion of participants achieving MCID in SGRQ total score

    Timeframe: Week 52

    Proportion of participants achieving MCID in SGRQ score (percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline).

  21. Proportion of participants achieving MCID in E-RS:COPD total score

    Timeframe: Week 52

    Proportion of participants achieving MCID in E-RS:COPD total score (percentage of participants with a decrease in E-RS:COPD total score of ≥ 2 points from baseline).

  22. Annualized rate of healthcare resource utilization

    Timeframe: Variable duration period up to study completion, approximately 3 years

    Annualized rate of healthcare resource utilization.

  23. Change from baseline in rescue medication

    Timeframe: Over 52 weeks

    Change from baseline (difference in mean number of puffs/day) in rescue medication use.

  24. Trough serum concentrations of tozorakimab

    Timeframe: Over 52 weeks

    Pharmacokinetics: concentrations of tozorakimab in trough serum.

  25. Presence of anti-drug antibodies

    Timeframe: Over 52 weeks

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

And 1 more, listed on the interactive page.

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 optimised inhaled dual or triple therapy 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. Radiological findings of pulmonary nodules suspicious for lung cancer, as per applicable guidances, without appropriate follow up prior to randomisation. Radiological findings suggestive of acute infection.
  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 active severe inflammatory bowel disease or colitis within one year prior to enrolment, or unexplained diarrhoea within the 4 weeks prior to randomisation.
  12. History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV 2.
  13. History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C)
  14. Evidence of active liver disease, including jaundice during screening.
  15. 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.
  16. Participants who have evidence of active TB.
  17. History of partial or total lung resection.
  18. Scheduled major surgical procedure during the course of the study.
  19. Participants that have previously received tozorakimab.
  20. 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.
Sources for eligibility
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  • Research SiteBirmingham, United States
  • Research SiteDecatur, United States
  • Research SiteSheffield, United States
  • Research SitePhoenix, United States
  • Research SiteTucson, United States
  • Research SiteYuma, United States
  • Research SiteLos Angeles, United States
  • Research SiteNewport Beach, United States
  • Research SiteSan Francisco, United States
  • Research SiteWestminster, United States
  • Research SiteAurora, United States
  • Research SiteBoulder, United States
  • Research SiteWashington D.C., United States
  • Research SiteBoynton Beach, United States
  • Research SiteCape Coral, United States
  • Research SiteLakeland, United States
  • Research SiteLakeland, United States
  • Research SiteNaples, United States
  • Research SiteOcala, United States
  • Research SiteOrmond Beach, United States
  • Research SiteAtlanta, United States
  • Research SiteLithonia, United States
  • Research SiteChampaign, United States
  • Research SiteChicago, United States
  • Research SiteChicago, United States

And 343 more, listed on the interactive page.

Sources for sites
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  • 2023
  • 2023-505543-39-00
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (2)