xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06040086</url>
    </required_header>
    <id_info>
      <org_study_id>D9180C00012</org_study_id>
      <secondary_id>2023-505543-39</secondary_id>
      <nct_id>NCT06040086</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations</brief_title>
    <acronym>MIRANDA</acronym>
    <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)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>AstraZeneca</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>AstraZeneca</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this Phase III study is to evaluate the efficacy and safety of tozorakimab&#xD;
        administered subcutaneously (SC) in adult participants with symptomatic COPD with a history&#xD;
        of ≥ 2 moderate or ≥ 1 severe exacerbations of COPD in the 12 months prior to enrolment.&#xD;
        Participants should be receiving optimised treatment with inhaled maintenance therapy&#xD;
        (ICS/LABA/LAMA triple therapy, or dual therapy if triple is not considered appropriate)&#xD;
        throughout at least the last 3 months prior to enrolment.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 22, 2023</start_date>
    <completion_date type="Anticipated">December 7, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 10, 2026</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers.</measure>
      <time_frame>Over 52 weeks</time_frame>
      <description>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]).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Annualized rate of moderate to severe COPD exacerbations in former or current smokers.</measure>
      <time_frame>Over 52 weeks</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in SGRQ total score from in former smokers</measure>
      <time_frame>Over 52 weeks</time_frame>
      <description>Difference in mean change from baseline in SGRQ total score in former smokers.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in SGRQ total score from in the overall population of current and former smokers.</measure>
      <time_frame>Over 52 weeks</time_frame>
      <description>Difference in mean change from baseline in SGRQ total score in the overall population of current and former smokers.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Annualized rate of severe COPD exacerbations in former smokers</measure>
      <time_frame>Variable duration period up to study completion, maximum of approximately 3 years</time_frame>
      <description>The rate ratio of severe COPD exacerbations will be assessed in former smokers.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Annualized rate of severe COPD exacerbations in former or current smokers</measure>
      <time_frame>Variable duration period up to study completion, maximum of approximately 3 years</time_frame>
      <description>The rate ratio of severe COPD exacerbations will be assessed in the overall population of current and former smokers.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in E-RS:COPD total score in former smokers</measure>
      <time_frame>Over 52 weeks</time_frame>
      <description>Difference in mean change in E-RS:COPD total score from baseline in former smokers.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in E-RS:COPD total score in former or current smokers</measure>
      <time_frame>Over 52 weeks</time_frame>
      <description>Difference in mean change in E-RS:COPD total score from baseline in the overall population of current and former smokers.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers</measure>
      <time_frame>Week 52, over 52 weeks</time_frame>
      <description>Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former or current smokers</measure>
      <time_frame>Week 52, over 52 weeks</time_frame>
      <description>Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in the overall population of current and former smokers.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to first moderate to severe COPD exacerbation</measure>
      <time_frame>Over 52 weeks</time_frame>
      <description>Time to first moderate to severe COPD exacerbation compared with placebo.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to first severe COPD exacerbation</measure>
      <time_frame>Variable duration period up to study completion, maximum of approximately 3 years</time_frame>
      <description>Time to first severe COPD exacerbation compared with placebo.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in CAT total score</measure>
      <time_frame>Week 52</time_frame>
      <description>Change from baseline in CAT total score compared with placebo.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants achieving MCID in CAT score</measure>
      <time_frame>Week 52</time_frame>
      <description>Proportion of participants achieving MCID in CAT score (percentage of participants with a decrease in CAT total score of ≥ 2 points from baseline).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants achieving MCID in SGRQ total score</measure>
      <time_frame>Week 52</time_frame>
      <description>Proportion of participants achieving MCID in SGRQ score (percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants achieving MCID in E-RS:COPD total score</measure>
      <time_frame>Week 52</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Annualized rate of healthcare resource utilization</measure>
      <time_frame>Variable duration period up to study completion, maximum of approximately 3 years</time_frame>
      <description>Annualized rate of healthcare resource utilization.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in rescue medication</measure>
      <time_frame>Over 52 weeks</time_frame>
      <description>Change from baseline (difference in mean number of puffs/day) in rescue medication use.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Trough serum concentrations of tozorakimab</measure>
      <time_frame>Over 52 weeks</time_frame>
      <description>Pharmacokinetics: concentrations of tozorakimab in trough serum.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Presence of anti-drug antibodies</measure>
      <time_frame>Over 52 weeks</time_frame>
      <description>Immunogenicity: presence of tozorakimab anti-drug antibodies in blood serum.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to death</measure>
      <time_frame>Variable duration period up to study completion, maximum of approximately 3 years</time_frame>
      <description>Time to death (all-cause mortality)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">1240</enrollment>
    <condition>Chronic Obstructive Pulmonary Disease (COPD)</condition>
    <arm_group>
      <arm_group_label>Tozorakimab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dosing subcutaneously tozorakimab</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Dosing subcutaneously with equivalent volume to tozorakimab</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo administered subcutaneously, equivalent volume to tozorakimab throughout the study.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tozorakimab</intervention_name>
      <description>Administered subcutaneously tozorakimab and placebo throughout the study.</description>
      <arm_group_label>Tozorakimab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Participant must be ≥ 40 years of age and capable of giving signed informed consent.&#xD;
  &#xD;
            2. Documented diagnosis of COPD for at least one year prior to enrolment.&#xD;
  &#xD;
            3. Post BD FEV1/FVC &lt; 0.70 and post-BD FEV1 &gt;20% of predicted normal value&#xD;
  &#xD;
            4. Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months&#xD;
               prior to enrolment.&#xD;
  &#xD;
            5. Documented optimised inhaled dual or triple therapy for at least 3 months prior to&#xD;
               enrolment.&#xD;
  &#xD;
            6. Smoking history of ≥ 10 pack-years.&#xD;
  &#xD;
            7. CAT total score ≥ 10, with each of the phlegm (sputum) and cough items with a score ≥&#xD;
               2&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Clinically important pulmonary disease other than COPD.&#xD;
  &#xD;
            2. Radiological findings suggestive of a respiratory disease other than COPD that is&#xD;
               significantly contributing to the participant's respiratory symptoms. Radiological&#xD;
               findings of pulmonary nodules suspicious for lung cancer, as per applicable guidances,&#xD;
               without appropriate follow up prior to randomisation. Radiological findings suggestive&#xD;
               of acute infection.&#xD;
  &#xD;
            3. Current diagnosis of asthma, prior history of asthma, or asthma-COPD overlap.&#xD;
               Childhood history of asthma is allowed and defined as asthma diagnosed and resolved&#xD;
               before the age of 18&#xD;
  &#xD;
            4. Any unstable disorder, including, but not limited to, cardiovascular,&#xD;
               gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious,&#xD;
               endocrine, metabolic, haematological, psychiatric disorder, major physical and/or&#xD;
               cognitive impairment that could affect safety, study findings or participants ability&#xD;
               to complete the study.&#xD;
  &#xD;
            5. COPD exacerbation, within 2 weeks prior to randomization, that was treated with&#xD;
               systemic corticosteroids and/or antibiotics, and/or led to hospitalization.&#xD;
  &#xD;
            6. Active significant infection within the 4 weeks prior to randomization, pneumonia&#xD;
               within 6 weeks prior to randomization, or medical condition that predisposes the&#xD;
               participant to infection.&#xD;
  &#xD;
            7. Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.&#xD;
  &#xD;
            8. Significant COVID-19 illness within the 6 months prior to enrolment.&#xD;
  &#xD;
            9. Unstable cardiovascular disorder.&#xD;
  &#xD;
           10. Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular&#xD;
               failure.&#xD;
  &#xD;
           11. History of active severe inflammatory bowel disease or colitis within one year prior&#xD;
               to enrolment, or unexplained diarrhoea within the 4 weeks prior to randomisation.&#xD;
  &#xD;
           12. History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV&#xD;
               2.&#xD;
  &#xD;
           13. History of positive test or treatment for hepatitis B or hepatitis C (except for cured&#xD;
               hepatitis C)&#xD;
  &#xD;
           14. Evidence of active liver disease, including jaundice during screening.&#xD;
  &#xD;
           15. Malignancy, current or within the past 5 years, except for adequately treated&#xD;
               non-invasive basal cell and squamous cell carcinoma of the skin and cervical&#xD;
               carcinoma-in-situ treated with apparent success more than one year prior to enrolment.&#xD;
               Suspected malignancy or undefined neoplasms.&#xD;
  &#xD;
           16. Participants who have evidence of active TB.&#xD;
  &#xD;
           17. History of partial or total lung resection.&#xD;
  &#xD;
           18. Scheduled major surgical procedure during the course of the study.&#xD;
  &#xD;
           19. Participants that have previously received tozorakimab.&#xD;
  &#xD;
           20. Any clinically significant abnormal findings in physical examination, vital signs,&#xD;
               ECG, or laboratory testing during the screening period, which in the opinion of the&#xD;
               investigator may put the participant at risk because of their participation in the&#xD;
               study, or may influence the results of the study, or the participant's ability to&#xD;
               complete the entire duration of the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>130 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>AstraZeneca Clinical Study Information Center</last_name>
      <phone>1-877-240-9479</phone>
      <email>information.center@astrazeneca.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Sheffield</city>
          <state>Alabama</state>
          <zip>35660</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Newport Beach</city>
          <state>California</state>
          <zip>92663</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Boynton Beach</city>
          <state>Florida</state>
          <zip>33435</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Ormond Beach</city>
          <state>Florida</state>
          <zip>32174</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Bowling Green</city>
          <state>Kentucky</state>
          <zip>42101</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>McKinney</city>
          <state>Texas</state>
          <zip>75069</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Brussels</city>
          <zip>1070</zip>
          <country>Belgium</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Edegem</city>
          <zip>2650</zip>
          <country>Belgium</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Mechelen</city>
          <zip>2800</zip>
          <country>Belgium</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Roeselare</city>
          <zip>8800</zip>
          <country>Belgium</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Sao Bernardo do Campo</city>
          <zip>09715090</zip>
          <country>Brazil</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Burlington</city>
          <state>Ontario</state>
          <zip>L7N 3V2</zip>
          <country>Canada</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Marburg</city>
          <zip>35037</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Athens</city>
          <zip>11521</zip>
          <country>Greece</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Exohi Thessaloniki</city>
          <zip>57010</zip>
          <country>Greece</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Heraklion</city>
          <zip>71409</zip>
          <country>Greece</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Ioannina</city>
          <zip>45500</zip>
          <country>Greece</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Thessaloniki</city>
          <zip>57010</zip>
          <country>Greece</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Cork</city>
          <zip>T12 DV56</zip>
          <country>Ireland</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Dublin</city>
          <zip>D09 V2N0</zip>
          <country>Ireland</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Dublin</city>
          <zip>D24 NR0A</zip>
          <country>Ireland</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Galway</city>
          <zip>H91 YR71</zip>
          <country>Ireland</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Arnhem</city>
          <zip>6815 AD</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Breda</city>
          <zip>4818 CK</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Den Bosch</city>
          <zip>5223 GZ</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Groningen</city>
          <zip>9728 NT</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Harderwijk</city>
          <zip>3844 DG</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Heerlen</city>
          <zip>6419 PC</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Roermond</city>
          <zip>6043 CV</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Rotterdam</city>
          <zip>3045 PM</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Rotterdam</city>
          <zip>3083 AN</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Zutphen</city>
          <zip>7207 AE</zip>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Belgium</country>
      <country>Brazil</country>
      <country>Canada</country>
      <country>Germany</country>
      <country>Greece</country>
      <country>Ireland</country>
      <country>Netherlands</country>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 25, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Chronic Obstructive Pulmonary Disease</keyword>
    <keyword>COPD</keyword>
    <keyword>tozorakimab</keyword>
    <keyword>MEDI3506</keyword>
    <keyword>exacerbations</keyword>
    <keyword>ICS</keyword>
    <keyword>LABA/LAMA</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lung Diseases</mesh_term>
      <mesh_term>Lung Diseases, Obstructive</mesh_term>
      <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_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:&#xD;
  https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.&#xD;
  Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_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 :&#xD;
  https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
      <ipd_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.</ipd_access_criteria>
      <ipd_url>https://vivli.org/</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06040086
  org study id: D9180C00012
  secondary id: 2023-505543-39
  nct id: NCT06040086
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers.
  time frame: Over 52 weeks
  description: 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]).
  measure: Annualized rate of moderate to severe COPD exacerbations in former or current smokers.
  time frame: Over 52 weeks
  description: 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.
  measure: Change from baseline in SGRQ total score from in former smokers
  time frame: Over 52 weeks
  description: Difference in mean change from baseline in SGRQ total score in former smokers.
  measure: Change from baseline in SGRQ total score from in the overall population of current and former smokers.
  time frame: Over 52 weeks
  description: Difference in mean change from baseline in SGRQ total score in the overall population of current and former smokers.
  measure: Annualized rate of severe COPD exacerbations in former smokers
  time frame: Variable duration period up to study completion, maximum of approximately 3 years
  description: The rate ratio of severe COPD exacerbations will be assessed in former smokers.
  measure: 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
  description: The rate ratio of severe COPD exacerbations will be assessed in the overall population of current and former smokers.
  measure: Change from baseline in E-RS:COPD total score in former smokers
  time frame: Over 52 weeks
  description: Difference in mean change in E-RS:COPD total score from baseline in former smokers.
  measure: Change from baseline in E-RS:COPD total score in former or current smokers
  time frame: Over 52 weeks
  description: Difference in mean change in E-RS:COPD total score from baseline in the overall population of current and former smokers.
  measure: Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers
  time frame: Week 52, over 52 weeks
  description: Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers.
  measure: Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former or current smokers
  time frame: Week 52, over 52 weeks
  description: Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in the overall population of current and former smokers.
  measure: Time to first moderate to severe COPD exacerbation
  time frame: Over 52 weeks
  description: Time to first moderate to severe COPD exacerbation compared with placebo.
  measure: Time to first severe COPD exacerbation
  time frame: Variable duration period up to study completion, maximum of approximately 3 years
  description: Time to first severe COPD exacerbation compared with placebo.
  measure: Change from baseline in CAT total score
  time frame: Week 52
  description: Change from baseline in CAT total score compared with placebo.
  measure: Proportion of participants achieving MCID in CAT score
  time frame: Week 52
  description: Proportion of participants achieving MCID in CAT score (percentage of participants with a decrease in CAT total score of ≥ 2 points from baseline).
  measure: Proportion of participants achieving MCID in SGRQ total score
  time frame: Week 52
  description: Proportion of participants achieving MCID in SGRQ score (percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline).
  measure: Proportion of participants achieving MCID in E-RS:COPD total score
  time frame: Week 52
  description: 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).
  measure: Annualized rate of healthcare resource utilization
  time frame: Variable duration period up to study completion, maximum of approximately 3 years
  description: Annualized rate of healthcare resource utilization.
  measure: Change from baseline in rescue medication
  time frame: Over 52 weeks
  description: Change from baseline (difference in mean number of puffs/day) in rescue medication use.
  measure: Trough serum concentrations of tozorakimab
  time frame: Over 52 weeks
  description: Pharmacokinetics: concentrations of tozorakimab in trough serum.
  measure: Presence of anti-drug antibodies
  time frame: Over 52 weeks
  description: Immunogenicity: presence of tozorakimab anti-drug antibodies in blood serum.
  measure: Time to death
  time frame: Variable duration period up to study completion, maximum of approximately 3 years
  description: Time to death (all-cause mortality)
  arm group label: Tozorakimab
  arm group type: Experimental
  description: Dosing subcutaneously tozorakimab
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Dosing subcutaneously with equivalent volume to tozorakimab
  intervention type: Drug
  intervention name: Placebo
  description: Placebo administered subcutaneously, equivalent volume to tozorakimab throughout the study.
  arm group label: Placebo
  intervention type: Drug
  intervention name: Tozorakimab
  description: Administered subcutaneously tozorakimab and placebo throughout the study.
  arm group label: Tozorakimab
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 130 Years
  healthy volunteers: No
  last name: AstraZeneca Clinical Study Information Center
  phone: 1-877-240-9479
  email: information.center@astrazeneca.com
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  country: Belgium
  country: Brazil
  country: Canada
  country: Germany
  country: Greece
  country: Ireland
  country: Netherlands
  country: United States
  responsible party type: Sponsor
  mesh term: Lung Diseases
  mesh term: Lung Diseases, Obstructive
  mesh term: Pulmonary Disease, Chronic Obstructive
  sharing ipd: Yes
  ipd 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.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd 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.
  ipd 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.
  ipd url: https://vivli.org/