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

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ClinicalTrials.gov Identifier: NCT06040086
Recruitment Status : Recruiting
First Posted : September 15, 2023
Last Update Posted : May 8, 2024
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease (COPD) Drug: Placebo Drug: Tozorakimab Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 22, 2023
Estimated Primary Completion Date : September 10, 2026
Estimated Study Completion Date : December 7, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD Lung Diseases

Arms and Interventions
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Arm Intervention/treatment
Experimental: Tozorakimab
Dosing subcutaneously tozorakimab
 Drug: Tozorakimab
Administered subcutaneously tozorakimab and placebo throughout the study.
Placebo Comparator: Placebo
Dosing subcutaneously with equivalent volume to tozorakimab
 Drug: Placebo
Placebo administered subcutaneously, equivalent volume to tozorakimab throughout the study.


Outcome Measures
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Primary Outcome Measures :
  1. Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers. [ Time Frame: 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]).


Secondary Outcome Measures :
  1. Annualized rate of moderate to severe COPD exacerbations in former or current smokers. [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: Variable duration period up to study completion, maximum of 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 [ Time Frame: Variable duration period up to study completion, maximum of 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Week 52, 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 [ Time Frame: Week 52, over 52 weeks ]
    Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in the overall population of current and former smokers.

  10. Time to first moderate to severe COPD exacerbation [ Time Frame: Over 52 weeks ]
    Time to first moderate to severe COPD exacerbation compared with placebo.

  11. Time to first severe COPD exacerbation [ Time Frame: Variable duration period up to study completion, maximum of approximately 3 years ]
    Time to first severe COPD exacerbation compared with placebo.

  12. Change from baseline in CAT total score [ Time Frame: Week 52 ]
    Change from baseline in CAT total score compared with placebo.

  13. Proportion of participants achieving MCID in CAT score [ Time Frame: 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).

  14. Proportion of participants achieving MCID in SGRQ total score [ Time Frame: 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).

  15. Proportion of participants achieving MCID in E-RS:COPD total score [ Time Frame: 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).

  16. Annualized rate of healthcare resource utilization [ Time Frame: Variable duration period up to study completion, maximum of approximately 3 years ]
    Annualized rate of healthcare resource utilization.

  17. Change from baseline in rescue medication [ Time Frame: Over 52 weeks ]
    Change from baseline (difference in mean number of puffs/day) in rescue medication use.

  18. Trough serum concentrations of tozorakimab [ Time Frame: Over 52 weeks ]
    Pharmacokinetics: concentrations of tozorakimab in trough serum.

  19. Presence of anti-drug antibodies [ Time Frame: Over 52 weeks ]
    Immunogenicity: presence of tozorakimab anti-drug antibodies in blood serum.

  20. Time to death [ Time Frame: Variable duration period up to study completion, maximum of approximately 3 years ]
    Time to death (all-cause mortality)


Eligibility Criteria
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Ages Eligible for Study:   40 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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

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. 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06040086


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
More Information
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT06040086    
Other Study ID Numbers: D9180C00012
2023-505543-39 ( EudraCT Number )
First Posted: September 15, 2023    Key Record Dates
Last Update Posted: May 8, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame:

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at :

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Chronic Obstructive Pulmonary Disease
COPD
tozorakimab
MEDI3506
 exacerbations
ICS
LABA/LAMA
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
 Chronic Disease
Disease Attributes
Pathologic Processes