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/NCT06020014</url>
    </required_header>
    <id_info>
      <org_study_id>D8210C00003</org_study_id>
      <nct_id>NCT06020014</nct_id>
    </id_info>
    <brief_title>Phase 2a Study to Assess the Efficacy and Safety of AZD4604 in Adult Patients With Moderate-to-Severe Asthma Uncontrolled on Medium-High Dose ICS-LABA</brief_title>
    <acronym>AJAX</acronym>
    <official_title>A Phase 2a Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AZD4604 Twice Daily for Twelve Weeks in Adult Patients With Moderate-to-Severe Asthma Uncontrolled on Medium-High Dose ICS-LABA</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>
        This is a Phase 2a, multicentre, randomised, placebo-controlled, double-blind, parallel-group&#xD;
        study to evaluate the efficacy, safety and PK of AZD4604 administered BID using a dry-powder&#xD;
        inhaler at one dose level over a 12-week Treatment period in adult participants with&#xD;
        uncontrolled moderate-to-severe asthma.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 3, 2023</start_date>
    <completion_date type="Anticipated">September 29, 2025</completion_date>
    <primary_completion_date type="Anticipated">September 29, 2025</primary_completion_date>
    <phase>Phase 2</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>Time to first CompEx Asthma event</measure>
      <time_frame>12 weeks</time_frame>
      <description>CompEx Asthma is a composite surrogate endpoint for exacerbations that captures: - acute worsening events based on a combination of events based on ePRO data (asthma symptoms and rescue medication use), PEF data, and severe asthma exacerbation events.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pre-BD FEV1</measure>
      <time_frame>12 weeks</time_frame>
      <description>Change from baseline in pre-bronchodilator forced expiratory volume in 1 second.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CAAT</measure>
      <time_frame>12 weeks</time_frame>
      <description>Change from baseline in the Chronic Airways Assessment Test (CAAT). The CAAT is an 8-item patient-reported outcome measure developed to measure health status in patients with asthma and COPD.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ACQ-6</measure>
      <time_frame>12 weeks</time_frame>
      <description>Change from baseline in the Asthma Control Questionnaire 6 (ACQ-6). The ACQ-6 has 6 questions (regarding asthma symptoms and rescue bronchodilator use). Answering the questions results in a score out of 6. A Score of 0 indicates complete control and 6 reflects severely uncontrolled disease.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average morning and average evening PEF</measure>
      <time_frame>12 weeks</time_frame>
      <description>Change from baseline in average morning and evening Peak Expiratory Flow (PEF) measurement.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Daily asthma symptom score (total, daytime, and night-time)</measure>
      <time_frame>12 weeks</time_frame>
      <description>Change from baseline in Daily asthma symptom score. Asthma symptoms are assessed (0 to 3 scale) twice daily, once in the morning and once in the evening.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to first CompEx acute worsening event</measure>
      <time_frame>12 weeks</time_frame>
      <description>Time to first CompEx Asthma acute worsening event.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CompEx event rate</measure>
      <time_frame>12 weeks</time_frame>
      <description>The number of CompEx Asthma events recorded in the 12-week period.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CompEx acute worsening event rate</measure>
      <time_frame>12 weeks</time_frame>
      <description>The number of CompEx Asthma acute worsening events recorded in the 12-week period.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">320</enrollment>
    <condition>Asthma</condition>
    <arm_group>
      <arm_group_label>Arm 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>AZD4604</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm 2</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>AZD4604</intervention_name>
      <description>AZD4604</description>
      <arm_group_label>Arm 1</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo</description>
      <arm_group_label>Arm 2</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. 18 to 80 years of age inclusive, at the time of signing the informed consent.&#xD;
  &#xD;
            2. Treated with medium-high dose ICS in combination with LABA at a stable dose for at&#xD;
               least 3 months prior to Visit 1.&#xD;
  &#xD;
            3. Documented history of ≥ 1 severe asthma exacerbation within 1 year prior to Visit 1.&#xD;
  &#xD;
            4. Morning pre-BD FEV1 between ≥ 40% and ≤ 90% predicted at Visit 1 and Visit 3.&#xD;
  &#xD;
            5. Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019&#xD;
               acceptability criteria.&#xD;
  &#xD;
            6. Documented evidence of asthma in the 10 years up to or including Visit 1.&#xD;
  &#xD;
            7. An ACQ-6 score ≥ 1.5 at Visit 1 and at Visit 3.&#xD;
  &#xD;
          9. Body weight of ≥ 40 kg and body mass index of &lt; 35 kg/m2. 10. Male and/or female:&#xD;
          Contraceptive use by males or females should be consistent with local regulations regarding&#xD;
          the methods of contraception for those participating in clinical studies.&#xD;
  &#xD;
          At the end of the Run-in period (Visit 3), participants must fulfil the following&#xD;
          additional criteria in order to be randomised into the study and enter the Treatment&#xD;
          period:&#xD;
  &#xD;
            1. Pre-BD FEV1 between ≥ 40% and ≤ 90% predicted.&#xD;
  &#xD;
            2. A pre-BD/pre-IMP dose FEV1 at Visit 3 that has not increased or decreased by 20% or&#xD;
               more from the pre-BD FEV1 recorded at Visit 1 and at Visit 2.&#xD;
  &#xD;
            3. An ACQ-6 score of ≥ 1.5.&#xD;
  &#xD;
            4. At least 80% compliance with usual asthma background medication during Run-in period&#xD;
               (from Visit 2 to Visit 3) based on the daily asthma ePROs.&#xD;
  &#xD;
            5. Minimum 80% compliance with daily eCOAs (electronic Clinical Outcome Assessments)&#xD;
               during the Run-in period and during the 14 days preceding Visit 3.&#xD;
  &#xD;
            6. For female participants, a negative urine pregnancy test prior to administration of&#xD;
               IMP.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. A severe asthma exacerbation within 8 weeks prior to randomisation.&#xD;
  &#xD;
            2. History of herpes zoster reactivation.&#xD;
  &#xD;
            3. Participants with a significant COVID-19 illness within 6 months of enrolment.&#xD;
  &#xD;
            4. Clinically important pulmonary disease other than asthma.&#xD;
  &#xD;
            5. Any disorder, including, but not limited to, cardiovascular, gastrointestinal,&#xD;
               hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic,&#xD;
               haematological, psychiatric, or major physical impairment that is not stable in the&#xD;
               opinion of the investigator and could:&#xD;
  &#xD;
                 -  affect the safety of the participant throughout the study,&#xD;
  &#xD;
                 -  influence the findings of the study or the interpretation, or&#xD;
  &#xD;
                 -  impede the participant's ability to complete the entire duration of study.&#xD;
  &#xD;
            6. Any clinically significant cardiac or cerebrovascular disease.&#xD;
  &#xD;
            7. History of venous thromboembolism.&#xD;
  &#xD;
            8. Participants who, as judged by the investigator, have evidence of active TB, or latent&#xD;
               TB without completion of an appropriate course of treatment or appropriate ongoing&#xD;
               prophylactic treatment.&#xD;
  &#xD;
            9. Participants with a recent history of, or who have a positive test for, infective&#xD;
               hepatitis or unexplained jaundice, or participants who have been treated for hepatitis&#xD;
               B, hepatitis C, or HIV.&#xD;
  &#xD;
           10. Current or prior history of alcohol or drug abuse (including marijuana), as judged by&#xD;
               the investigator.&#xD;
  &#xD;
           11. History of malignancy other than superficial basal cell carcinoma.&#xD;
  &#xD;
           12. Treatment with systemic corticosteroid within 4 weeks (oral) or 8 weeks&#xD;
               (intramuscular) before Visit 1.&#xD;
  &#xD;
           13. Any immunosuppressive therapy within 12 weeks prior to Visit 1.&#xD;
  &#xD;
           14. Treatment with marketed biologics within 6 months of Visit 1 or 5 half-lives,&#xD;
               whichever is longer.&#xD;
  &#xD;
           15. Inhaled corticosteroid plus fast-acting β2 agonist as a reliever is not allowed 15&#xD;
               days prior to Visit 1, during Screening/Run-in and throughout the Treatment period and&#xD;
               preferably 1 week after the last dose of IMP.&#xD;
  &#xD;
           16. Live, attenuated, or mRNA vaccines within 4 weeks of Visit 1.&#xD;
  &#xD;
           17. Immunoglobulin or blood products within 4 weeks of Visit 1.&#xD;
  &#xD;
           18. Any immunotherapy within 6 months of Visit 1, except for stable maintenance dose&#xD;
               allergen-specific immunotherapy started at least 4 weeks prior to Visit 1 and expected&#xD;
               to continue through to the end of the Follow-up period.&#xD;
  &#xD;
           19. Participant treated with any investigational drug within 4 months or 5 half-lives,&#xD;
               whichever is longer, prior to Visit 1.&#xD;
  &#xD;
           20. Participants with a known hypersensitivity to AZD4604 or any of the excipients of the&#xD;
               product.&#xD;
  &#xD;
           21. Abnormal findings identified on physical examination, ECG, or laboratory testing.&#xD;
  &#xD;
           22. For female participants only - currently pregnant (confirmed with positive pregnancy&#xD;
               test) or breast-feeding.&#xD;
  &#xD;
           23. Current smokers or participants with smoking history ≥ 10 pack-years.&#xD;
  &#xD;
           24. Participants with a known long-term exposure to occupational asbestos, silica, radon,&#xD;
               heavy metals, and polycyclic aromatic hydrocarbons.&#xD;
  &#xD;
           25. Positive family history of lung cancer.&#xD;
  &#xD;
           26. Positive urine cotinine test or exhaled carbon monoxide test at Visit 1 and at any&#xD;
               timepoint throughout the study.&#xD;
  &#xD;
           27. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
               staff and/or staff at the study site).&#xD;
  &#xD;
           28. Judgement by the investigator that the participant should not participate in the study&#xD;
               if the participant is unlikely to comply with study procedures, restrictions, and&#xD;
               requirements.&#xD;
  &#xD;
           29. Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days&#xD;
               before Visit 1.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 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>Stockton</city>
          <state>California</state>
          <zip>95207</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>New Bern</city>
          <state>North Carolina</state>
          <zip>28562</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Houston</city>
          <state>Texas</state>
          <zip>77074</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Alberdi</city>
          <zip>X5033DCE</zip>
          <country>Argentina</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>Berlin</city>
          <zip>10367</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Berlin</city>
          <zip>12159</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Berlin</city>
          <zip>12203</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Berlin</city>
          <zip>13187</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Cottbus</city>
          <zip>03050</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Darmstadt</city>
          <zip>64283</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Frankfurt am Main</city>
          <zip>60596</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Koblenz</city>
          <zip>56068</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Mainz</city>
          <zip>55128</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>München</city>
          <zip>81377</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Peine</city>
          <zip>31224</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Schwerin</city>
          <zip>19055</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Kajang</city>
          <zip>43000</zip>
          <country>Malaysia</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Kota Bahru</city>
          <zip>15586</zip>
          <country>Malaysia</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Kuala Lumpur</city>
          <zip>59100</zip>
          <country>Malaysia</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Bangkok</city>
          <zip>10400</zip>
          <country>Thailand</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Chiang Mai</city>
          <zip>50200</zip>
          <country>Thailand</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Hat Yai</city>
          <zip>90110</zip>
          <country>Thailand</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Khlong Luang</city>
          <zip>12120</zip>
          <country>Thailand</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Khon Kaen</city>
          <zip>40002</zip>
          <country>Thailand</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Argentina</country>
      <country>Brazil</country>
      <country>Germany</country>
      <country>Malaysia</country>
      <country>Thailand</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>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>asthma, Janus kinase inhibitor</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Asthma</mesh_term>
    </condition_browse>
    <!-- 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/NCT06020014
  org study id: D8210C00003
  nct id: NCT06020014
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a Phase 2a, multicentre, randomised, placebo-controlled, double-blind, parallel-group
        study to evaluate the efficacy, safety and PK of AZD4604 administered BID using a dry-powder
        inhaler at one dose level over a 12-week Treatment period in adult participants with
        uncontrolled moderate-to-severe asthma.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Time to first CompEx Asthma event
  time frame: 12 weeks
  description: CompEx Asthma is a composite surrogate endpoint for exacerbations that captures: - acute worsening events based on a combination of events based on ePRO data (asthma symptoms and rescue medication use), PEF data, and severe asthma exacerbation events.
  measure: Pre-BD FEV1
  time frame: 12 weeks
  description: Change from baseline in pre-bronchodilator forced expiratory volume in 1 second.
  measure: CAAT
  time frame: 12 weeks
  description: Change from baseline in the Chronic Airways Assessment Test (CAAT). The CAAT is an 8-item patient-reported outcome measure developed to measure health status in patients with asthma and COPD.
  measure: ACQ-6
  time frame: 12 weeks
  description: Change from baseline in the Asthma Control Questionnaire 6 (ACQ-6). The ACQ-6 has 6 questions (regarding asthma symptoms and rescue bronchodilator use). Answering the questions results in a score out of 6. A Score of 0 indicates complete control and 6 reflects severely uncontrolled disease.
  measure: Average morning and average evening PEF
  time frame: 12 weeks
  description: Change from baseline in average morning and evening Peak Expiratory Flow (PEF) measurement.
  measure: Daily asthma symptom score (total, daytime, and night-time)
  time frame: 12 weeks
  description: Change from baseline in Daily asthma symptom score. Asthma symptoms are assessed (0 to 3 scale) twice daily, once in the morning and once in the evening.
  measure: Time to first CompEx acute worsening event
  time frame: 12 weeks
  description: Time to first CompEx Asthma acute worsening event.
  measure: CompEx event rate
  time frame: 12 weeks
  description: The number of CompEx Asthma events recorded in the 12-week period.
  measure: CompEx acute worsening event rate
  time frame: 12 weeks
  description: The number of CompEx Asthma acute worsening events recorded in the 12-week period.
  arm group label: Arm 1
  arm group type: Experimental
  description: AZD4604
  arm group label: Arm 2
  arm group type: Placebo Comparator
  description: Placebo
  intervention type: Drug
  intervention name: AZD4604
  description: AZD4604
  arm group label: Arm 1
  intervention type: Other
  intervention name: Placebo
  description: Placebo
  arm group label: Arm 2
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: AstraZeneca Clinical Study Information Center
  phone: 1-877-240-9479
  email: information.center@astrazeneca.com
  facility: 
  facility: 
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  country: Argentina
  country: Brazil
  country: Germany
  country: Malaysia
  country: Thailand
  country: United States
  responsible party type: Sponsor
  mesh term: Asthma