<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/NCT04507256</url>
  </required_header>
  <id_info>
    <org_study_id>D8850C00001</org_study_id>
    <nct_id>NCT04507256</nct_id>
  </id_info>
  <brief_title>AZD7442 - a Potential Combination Therapy for the Prevention and Treatment of COVID-19</brief_title>
  <official_title>A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AZD7442 in Healthy Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Parexel</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this first-in-humans dose escalation study, AZD7442 (AZD8895 + AZD1061) will be evaluated&#xD;
      for safety, tolerability, pharmacokinetics, and generation of anti-drug antibodies (ADAs).&#xD;
      The study is intended to enable future studies of AZD7442's efficacy in preventing and&#xD;
      treating COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I, first time in human, randomised, double-blind, placebo-controlled, and&#xD;
      dose escalation study.&#xD;
&#xD;
      The study will comprise of:&#xD;
&#xD;
        1. A Screening Period of up to 27 days (Day -28 through Day -2);&#xD;
&#xD;
        2. A Treatment Period during which participants will be resident at the Clinical Unit from&#xD;
           Day -1, 1 day before Investigational Medicinal Product (IMP) administration (on Day 1)&#xD;
           until at least 24 hours after IMP administration, will be discharged on Day 2 after all&#xD;
           safety evaluations have been completed, and&#xD;
&#xD;
        3. A Follow up Period lasting 360 days (through to Day 361) after the IMP dose.&#xD;
&#xD;
      The study will be conducted at a single study centre in United Kingdom.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 18, 2020</start_date>
  <completion_date type="Actual">October 19, 2021</completion_date>
  <primary_completion_date type="Actual">October 19, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>The study will be blinded for all placebo controlled dose groups, ie, the Principal Investigator (PI), all clinical staff involved in the clinical study, the participants, and the study monitor will remain blinded, unless safety concerns or a regulatory requirement necessitate unblinding.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse events (AEs) and serious AEs</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>Safety and tolerability will be evaluated in terms of number of participants with AEs/SAEs, abnormal values of vital signs, safety laboratory parameters, 12 lead safety electrocardiogram, injection site reactions, and physical examination.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Observed maximum concentration (Cmax) (IV infusion)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>Cmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach maximum concentration (Tmax) (IV infusion)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>Tmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half life, estimated as (ln2)/λz (t½λz) (IV infusion)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>t½λz will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration curve from time zero to the time of last quantifiable concentration (AUClast) (IV infusion)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>AUClast will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration time curve from time zero extrapolated to infinity (AUCinf) (IV infusion)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>AUCinf will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution at steady state (Vss) (IV infusion)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>Vss will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution at terminal phase (Vz) (IV infusion)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>Vz will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic clearance (CL) (IV infusion)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>CL will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (IM injection)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>Cmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax (IM injection)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>Tmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t½λz (IM injection)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>t½λz will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast (IM injection)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>AUClast will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCinf (IM injection)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>AUCinf will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extravascular systemic clearance (CL/F) (IM injection)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>CL/F will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioavailability (F) (IM injection)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>F will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extravascular terminal-phase volume of distribution (Vz/F) (IM injection)</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>Vz/F will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and percentage of participants who are ADA positive</measure>
    <time_frame>From Day 1 up to last follow-up day (Day 361)</time_frame>
    <description>The incidence of ADAs to AZD7442 in serum will be summarised by number and percentage of participants who are ADA positive. The ADA titer will be listed by participant at different time points.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>AZD7442</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive AZD7442 doses across five fixed-dose cohorts via intravenous (IV) infusions (three cohorts will be administered sequentially, and one cohort will receive co-administration of AZD8895 + AZD1061, mixed into a single infusion) and direct gluteal intramuscular (IM) injections (administered sequentially).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be administered to participants across five fixed-dose cohorts similar to the active treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>AZD7442</intervention_name>
    <description>Participants randomized to AZD7442 will be administered dose 1, each in Cohort 1a (IM) and Cohort 1b (IV). Participants in Cohort 2 and 3 will receive AZD7442 (IV) doses 2 and 3, respectively. Participants in Cohort 4 will receive AZD7442 (IV) dose 4.</description>
    <arm_group_label>AZD7442</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants randomised to placebo will receive the same volume of solution as participants on active treatment.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent and any locally required authorisation obtained from the&#xD;
             participant prior to performing any protocol-related procedures, including screening&#xD;
             evaluations.&#xD;
&#xD;
          -  Negative SARS-CoV-2 qRT-PCR and/or serology tests prior to randomisation.&#xD;
&#xD;
          -  Weight ≥ 50 kg and ≤ 110 kg at screening, including a BMI of ≥ 18.0 to ≤ 30.0 kg/m^2.&#xD;
&#xD;
          -  Healthy by medical history, physical examination, and baseline safety laboratory&#xD;
             studies, according to the judgement of the PI.&#xD;
&#xD;
          -  Electrocardiogram without clinically significant abnormalities at screening.&#xD;
&#xD;
          -  Able to complete the Follow-up Period through Day 361.&#xD;
&#xD;
          -  Females of childbearing potential who are sexually active with a non-sterilised male&#xD;
             partner must have used a highly effective method of contraception for at least 28 days&#xD;
             prior to dosing with IMP and must agree to continue using such precautions until the&#xD;
             Final Follow-up Visit. Periodic abstinence, the rhythm method, and the withdrawal&#xD;
             method are not acceptable methods of contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hypersensitivity to any component of the IMP.&#xD;
&#xD;
          -  History of allergic disease or reactions likely to be exacerbated by any component of&#xD;
             the IMP.&#xD;
&#xD;
          -  Previous hypersensitivity, infusion-related reaction or severe adverse reaction&#xD;
             following administration of a mAbs.&#xD;
&#xD;
          -  Acute (time-limited) illness, including fever above 37.5°C (99.5 °F), on day prior to&#xD;
             or day of planned dosing; participants excluded for transient acute illness may be&#xD;
             dosed if illness resolves within the 27-day Screening Period or may be rescreened&#xD;
             once.&#xD;
&#xD;
          -  Any drug therapy within 7 days prior to Day 1 (except contraceptives or a single use&#xD;
             of acetaminophen, aspirin, antihistamine, or combination over the counter (OTC)&#xD;
             product that contains acetaminophen with an antihistamine, or OTC nonsteroidal&#xD;
             anti-inflammatory agent at a dose equal to or lower than that recommended on the&#xD;
             package). Vitamins and other nutritional supplements that are not newly introduced,&#xD;
             ie, have been taken for at least 30 days prior to enrolment, are not exclusionary.&#xD;
&#xD;
          -  Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 2 months&#xD;
             prior to screening.&#xD;
&#xD;
          -  Receipt of immunoglobulin or blood products within 6 months prior to screening.&#xD;
&#xD;
          -  SARS CoV-2 or COVID-19:&#xD;
&#xD;
               -  Participants with any confirmed current or previous COVID-19 infection before&#xD;
                  randomisation.&#xD;
&#xD;
               -  Participant has clinical signs and symptoms consistent with COVID-19, eg, fever,&#xD;
                  dry cough, dyspnoea, sore throat, fatigue or confirmed infection by appropriate&#xD;
                  laboratory test within the last 4 weeks prior to screening or on admission.&#xD;
&#xD;
               -  Any prior receipt of investigational or licensed vaccine indicated for the&#xD;
                  prevention of SARS CoV-2 or COVID-19 or expected receipt during the period of&#xD;
                  study follow up.&#xD;
&#xD;
          -  Receipt of any IMP in the preceding 90 days or expected receipt of IMP during the&#xD;
             period of study follow-up, or concurrent participation in another interventional&#xD;
             study.&#xD;
&#xD;
          -  Previous receipt of a mAb within 6 months, or five antibody half lives (whichever is&#xD;
             longer), prior to study start.&#xD;
&#xD;
          -  Immunodeficiency due to illness, including Human immunodeficiency virus (HIV)&#xD;
             infection, or due to drugs, including any course of glucocorticoid therapy exceeding 2&#xD;
             weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6&#xD;
             months prior to screening. HIV testing must be negative at screening.&#xD;
&#xD;
          -  Either history of active infection with hepatitis B or C or positive test for&#xD;
             hepatitis C or for hepatitis B surface antigen at screening.&#xD;
&#xD;
          -  History of infection with SARS or MERS.&#xD;
&#xD;
          -  Aspartate aminotransferase, ALT, or serum creatinine above the ULN; bilirubin and ALP&#xD;
             &gt;1.5 × ULN.&#xD;
&#xD;
          -  Haemoglobin or platelet count below the LLN at screening. White blood cell or&#xD;
             neutrophil count outside normal references ranges.&#xD;
&#xD;
          -  History of malignancy.&#xD;
&#xD;
          -  Any laboratory value in the screening panel that, in the opinion of the PI, is&#xD;
             clinically significant or might confound analysis of study results.&#xD;
&#xD;
          -  Pregnant or nursing female.&#xD;
&#xD;
          -  History of alcohol or drug abuse within the past 2 years that, according to the PI,&#xD;
             might affect assessments of safety or ability of participant to comply with all study&#xD;
             requirements OR positive urine drug or alcohol screening.&#xD;
&#xD;
          -  Any condition that, in the opinion of the PI, might compromise participant safety or&#xD;
             interfere with evaluation of the IMP or interpretation of participant safety or study&#xD;
             results.&#xD;
&#xD;
          -  Employees of the sponsor, clinical study site, or any other individuals involved with&#xD;
             the conduct of the study, or immediate family members of such individuals.&#xD;
&#xD;
          -  Absence of suitable veins for blood sampling (IM and IV cohorts) and administration of&#xD;
             IMP (IV cohorts).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pablo Forte Soto, MD, MSc, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Parexel EPCU (London)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Harrow</city>
        <zip>HA1 3UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 7, 2020</study_first_submitted>
  <study_first_submitted_qc>August 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2020</study_first_posted>
  <last_update_submitted>October 26, 2021</last_update_submitted>
  <last_update_submitted_qc>October 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Coronavirus</keyword>
  <keyword>Severe acute respiratory syndrome coronavirus 2</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Safety and tolerability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cilgavimab and tixagevimab drug combination</mesh_term>
  </intervention_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 requests 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_description>
    <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at 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 deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </patient_data>
  <pending_results>
    <submitted>October 7, 2022</submitted>
    <returned>August 25, 2023</returned>
    <submitted>September 15, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04507256
org study id: D8850C00001
nct id: NCT04507256
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In this first-in-humans dose escalation study, AZD7442 (AZD8895 + AZD1061) will be evaluated
      for safety, tolerability, pharmacokinetics, and generation of anti-drug antibodies (ADAs).
      The study is intended to enable future studies of AZD7442's efficacy in preventing and
      treating COVID-19.
This is a Phase I, first time in human, randomised, double-blind, placebo-controlled, and
      dose escalation study.

      The study will comprise of:

        1. A Screening Period of up to 27 days (Day -28 through Day -2);

        2. A Treatment Period during which participants will be resident at the Clinical Unit from
           Day -1, 1 day before Investigational Medicinal Product (IMP) administration (on Day 1)
           until at least 24 hours after IMP administration, will be discharged on Day 2 after all
           safety evaluations have been completed, and

        3. A Follow up Period lasting 360 days (through to Day 361) after the IMP dose.

      The study will be conducted at a single study centre in United Kingdom.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: The study will be blinded for all placebo controlled dose groups, ie, the Principal Investigator (PI), all clinical staff involved in the clinical study, the participants, and the study monitor will remain blinded, unless safety concerns or a regulatory requirement necessitate unblinding.
measure: Number of participants with adverse events (AEs) and serious AEs
time frame: From Day 1 up to last follow-up day (Day 361)
description: Safety and tolerability will be evaluated in terms of number of participants with AEs/SAEs, abnormal values of vital signs, safety laboratory parameters, 12 lead safety electrocardiogram, injection site reactions, and physical examination.
measure: Observed maximum concentration (Cmax) (IV infusion)
time frame: From Day 1 up to last follow-up day (Day 361)
description: Cmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Time to reach maximum concentration (Tmax) (IV infusion)
time frame: From Day 1 up to last follow-up day (Day 361)
description: Tmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Terminal elimination half life, estimated as (ln2)/λz (t½λz) (IV infusion)
time frame: From Day 1 up to last follow-up day (Day 361)
description: t½λz will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Area under the concentration curve from time zero to the time of last quantifiable concentration (AUClast) (IV infusion)
time frame: From Day 1 up to last follow-up day (Day 361)
description: AUClast will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Area under the concentration time curve from time zero extrapolated to infinity (AUCinf) (IV infusion)
time frame: From Day 1 up to last follow-up day (Day 361)
description: AUCinf will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Volume of distribution at steady state (Vss) (IV infusion)
time frame: From Day 1 up to last follow-up day (Day 361)
description: Vss will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Volume of distribution at terminal phase (Vz) (IV infusion)
time frame: From Day 1 up to last follow-up day (Day 361)
description: Vz will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Systemic clearance (CL) (IV infusion)
time frame: From Day 1 up to last follow-up day (Day 361)
description: CL will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Cmax (IM injection)
time frame: From Day 1 up to last follow-up day (Day 361)
description: Cmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Tmax (IM injection)
time frame: From Day 1 up to last follow-up day (Day 361)
description: Tmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: t½λz (IM injection)
time frame: From Day 1 up to last follow-up day (Day 361)
description: t½λz will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: AUClast (IM injection)
time frame: From Day 1 up to last follow-up day (Day 361)
description: AUClast will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: AUCinf (IM injection)
time frame: From Day 1 up to last follow-up day (Day 361)
description: AUCinf will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Extravascular systemic clearance (CL/F) (IM injection)
time frame: From Day 1 up to last follow-up day (Day 361)
description: CL/F will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Bioavailability (F) (IM injection)
time frame: From Day 1 up to last follow-up day (Day 361)
description: F will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Extravascular terminal-phase volume of distribution (Vz/F) (IM injection)
time frame: From Day 1 up to last follow-up day (Day 361)
description: Vz/F will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
measure: Number and percentage of participants who are ADA positive
time frame: From Day 1 up to last follow-up day (Day 361)
description: The incidence of ADAs to AZD7442 in serum will be summarised by number and percentage of participants who are ADA positive. The ADA titer will be listed by participant at different time points.
arm group label: AZD7442
arm group type: Experimental
description: Participants will receive AZD7442 doses across five fixed-dose cohorts via intravenous (IV) infusions (three cohorts will be administered sequentially, and one cohort will receive co-administration of AZD8895 + AZD1061, mixed into a single infusion) and direct gluteal intramuscular (IM) injections (administered sequentially).
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo will be administered to participants across five fixed-dose cohorts similar to the active treatment.
intervention type: Combination Product
intervention name: AZD7442
description: Participants randomized to AZD7442 will be administered dose 1, each in Cohort 1a (IM) and Cohort 1b (IV). Participants in Cohort 2 and 3 will receive AZD7442 (IV) doses 2 and 3, respectively. Participants in Cohort 4 will receive AZD7442 (IV) dose 4.
arm group label: AZD7442
intervention type: Other
intervention name: Placebo
description: Participants randomised to placebo will receive the same volume of solution as participants on active treatment.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pablo Forte Soto, MD, MSc, PhD
role: Principal Investigator
affiliation: Parexel EPCU (London)
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Cilgavimab and tixagevimab drug combination
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 requests 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 time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma 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 deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home
submitted: October 7, 2022
returned: August 25, 2023
submitted: September 15, 2023