<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/NCT03272165</url>
  </required_header>
  <id_info>
    <org_study_id>D6340C00001</org_study_id>
    <nct_id>NCT03272165</nct_id>
  </id_info>
  <brief_title>Single Ascending Dose Study of MEDI1341 in Healthy Volunteers</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of MEDI1341 in Healthy Male and Female Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Covance</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>MMS Holdings, Inc</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Catalent</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </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 study of single ascending intravenous doses of MEDI1341 or placebo in up to 48&#xD;
      healthy volunteers, aged 18 to 65 years. The study will include up to 6 planned cohorts; each&#xD;
      cohort will comprise 8 participants.&#xD;
&#xD;
      Each participant will receive a single 60 minute intravenous infusion of MEDI1341 or placebo&#xD;
      and will undergo scheduled assessments over a period of 13 weeks.&#xD;
&#xD;
      The main aim of the study is to assess the safety and tolerability of single doses of&#xD;
      MEDI1341 in healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, placebo-controlled study of single ascending intravenous&#xD;
      doses of MEDI1341 in male and nonfertile female healthy volunteers, aged 18 to 65 years.&#xD;
&#xD;
      The study will include up to 6 planned cohorts; each cohort will comprise 8 participants.&#xD;
      Within each cohort, 6 participants will be randomized to receive MEDI1341 and 2 will be&#xD;
      randomized to receive placebo. A Safety Review Committee will review data from each cohort&#xD;
      before progression to the next higher dose cohort occurs. On Day 1, each randomized&#xD;
      participant will receive a single 60 minute intravenous infusion of MEDI1341 or placebo and&#xD;
      will undergo scheduled safety, pharmacokinetic, pharmacodynamic, and immunogenicity&#xD;
      assessments. Additional study assessments will occur on Days 2, 4, 8, 15, 22, 29, 43, 57, and&#xD;
      92.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 17, 2017</start_date>
  <completion_date type="Actual">March 31, 2021</completion_date>
  <primary_completion_date type="Actual">March 31, 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>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants are randomized to one of two groups within a cohort of 8 participants (N=6 MEDI1341; N=2 placebo)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)</measure>
    <time_frame>Day 1 through 92 days after a single dose of study drug</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Abnormal Vital Signs, Physical and Neurological Examinations, and Body Weight Measurements Reported as TEAEs</measure>
    <time_frame>Day 1 through 92 days after a single dose of study drug</time_frame>
    <description>Vital signs assessment included body temperature, respiration rate, pulse rate, and blood pressure. Participants with abnormal vital signs, physical and neurological examinations, and body weight measurements reported as TEAEs are reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline in 12-Lead Electrocardiogram (ECG) Data in Paper and Digital Recordings (PR Interval, QRS Duration, QT Interval, QTcF Interval, and RR Interval)</measure>
    <time_frame>12-lead paper ECG: Baseline (Day -49) to Day 92; Digital ECG: Baseline (Day 1) to Day 92</time_frame>
    <description>Changes from baseline in 12-Lead ECG data in paper recordings (PR interval, QRS duration, QT interval, and QTcF interval) and digital recordings (PR interval, QRS duration, QT interval, QTcF interval, and RR interval) are reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline in Heart Rate by 12-Lead ECG in Paper and Digital Recordings</measure>
    <time_frame>12-lead paper ECG: Baseline (Day -49) to Day 92; Digital ECG: Baseline (Day 1) to Day 92</time_frame>
    <description>Change from baseline in heart rate by 12-Lead ECG in paper and digital recordings are reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs</measure>
    <time_frame>Day 1 through 92 days after a single dose of study drug</time_frame>
    <description>Laboratory assessment included hematology, clinical chemistry, and urinalysis. Participants with abnormal laboratory parameters reported as TEAEs are reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Abnormal Findings for Ophthalmic Assessment (Ophthalmic Examination and Slit-lamp Examination) for Placebo and Cohorts 4 to 6 at Follow-up Visit</measure>
    <time_frame>Follow-up Visit (Day 57)</time_frame>
    <description>Number of abnormal findings for ophthalmic assessment (ophthalmic examination and slit-lamp examination) at follow-up visit (Day 57) are reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intraocular Pressure at Screening for Placebo and Cohorts 4 to 6</measure>
    <time_frame>Screening (Day -49)</time_frame>
    <description>Intraocular pressure at Screening (Day -49) is reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intraocular Pressure at Day 29 for Placebo and Cohorts 4 to 6</measure>
    <time_frame>Day 29</time_frame>
    <description>Intraocular pressure at Day 29 is reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intraocular Pressure at Day 92 for Placebo and Cohorts 4 to 6</measure>
    <time_frame>Day 92</time_frame>
    <description>Intraocular pressure at Day 92 is reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Injection Site Reactions</measure>
    <time_frame>Day 1</time_frame>
    <description>Participants who had injection site reactions (bleeding, bruising, erythema, swelling, or induration) on Day 1 are reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Visual Analogue Scale (VAS) Pain Score for Site Reaction Pain</measure>
    <time_frame>Day 1 (within 24 hours after end of infusion)</time_frame>
    <description>The VAS (0 to 10 cm) was used to describe reaction site pain. The score 0 means 'no pain at all' and 10 score means 'worst pain imaginable'. The higher the VAS score, the greater the reaction site pain experienced.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Suicidal Ideation and Suicidal Behavior Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>Screening (Day -49) through 92 days after a single dose of study drug</time_frame>
    <description>The C-SSRS is a scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviours, and has a binary response (yes/no).&#xD;
Suicidal Ideation: a &quot;yes&quot; answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent.&#xD;
Suicidal Behaviour: a &quot;yes&quot; answer to any of 5 suicidal behaviour questions: preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt (non-fatal), completed suicide.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Montreal Cognitive Assessment (MoCA) Total Score at Screening (Day -1)</measure>
    <time_frame>Screening (Day -1)</time_frame>
    <description>The MoCA is s standardized cognitive screening tool for mild cognitive impairment and dementia. The total score was used as outcome measure and this score ranges from 0-31, with higher scores representing better cognitive ability and scores below 26 were considered as cognitive dysfunction.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With MoCA Total Score at Day 92</measure>
    <time_frame>Day 92</time_frame>
    <description>The MoCA is s standardized cognitive screening tool for mild cognitive impairment and dementia. The total score was used as outcome measure and this score ranges from 0-31, with higher scores representing better cognitive ability and scores below 26 were considered as cognitive dysfunction.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Serum Concentration (Cmax) of MEDI1341</measure>
    <time_frame>Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92</time_frame>
    <description>The Cmax of MEDI1341 is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Serum Concentration (tmax) of MEDI1341</measure>
    <time_frame>Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92</time_frame>
    <description>The tmax of MEDI1341 is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC0-t) of MEDI1341</measure>
    <time_frame>Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92</time_frame>
    <description>The AUC0-t of MEDI1341 is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of MEDI1341</measure>
    <time_frame>Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92</time_frame>
    <description>The AUC0-∞ of MEDI1341 is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-life (t1/2λz) of MEDI1341</measure>
    <time_frame>Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92</time_frame>
    <description>The t1/2λz of MEDI1341 is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Clearance (CL) of MEDI1341</measure>
    <time_frame>Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92</time_frame>
    <description>The CL of MEDI1341 is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution at Steady State (Vss) of MEDI1341</measure>
    <time_frame>Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92</time_frame>
    <description>The Vss of MEDI1341 is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Residence Time (MRT) of MEDI1341</measure>
    <time_frame>Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92</time_frame>
    <description>The MRT of MEDI1341 is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change From Baseline in Plasma Concentrations of Total α-synuclein</measure>
    <time_frame>Baseline (Day 1 predose) through Day 92</time_frame>
    <description>Maximum change from baseline through Day 92 and change from baseline at Day 92 in plasma concentrations of total α-synuclein are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change From Baseline in Cerebrospinal Fluid Concentrations of Free α-synuclein</measure>
    <time_frame>Baseline (Day 1 predose) and Day 29</time_frame>
    <description>Change from baseline in cerebrospinal fluid concentrations of free α-synuclein is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Positive Antidrug Antibodies (ADAs) to MEDI1341 by Titer Levels at Day 92</measure>
    <time_frame>Day 92</time_frame>
    <description>Percentage of participants with positive ADAs to MEDI1341 by titer levels are reported.</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive a single intravenous (IV) infusion of placebo matched to MEDI1341 and will be followed up for 13 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1: MEDI1341 Dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single IV infusion of MEDI1341 Dose 1 and will be followed up for 13 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: MEDI1341 Dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single IV infusion of MEDI1341 Dose 2 and will be followed up for 13 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3: MEDI1341 Dose 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single IV infusion of MEDI1341 Dose 3 and will be followed up for 13 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4: MEDI1341 Dose 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single IV infusion of MEDI1341 Dose 4 and will be followed up for 13 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5: MEDI1341 Dose 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single IV infusion of MEDI1341 Dose 5 and will be followed up for 13 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 6: MEDI1341 Dose 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single IV infusion of MEDI1341 Dose 6 and will be followed up for 13 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MEDI1341</intervention_name>
    <description>Participants will receive IV infusion of MEDI1341 doses as stated in the arms' description.</description>
    <arm_group_label>Cohort 1: MEDI1341 Dose 1</arm_group_label>
    <arm_group_label>Cohort 2: MEDI1341 Dose 2</arm_group_label>
    <arm_group_label>Cohort 3: MEDI1341 Dose 3</arm_group_label>
    <arm_group_label>Cohort 4: MEDI1341 Dose 4</arm_group_label>
    <arm_group_label>Cohort 5: MEDI1341 Dose 5</arm_group_label>
    <arm_group_label>Cohort 6: MEDI1341 Dose 6</arm_group_label>
    <other_name>TAK-341</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive IV infusion of placebo matched to MEDI1341.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must be healthy, with no clinically significant abnormality identified on&#xD;
             the medical or laboratory evaluation at screening&#xD;
&#xD;
          -  Participants must weigh ≥50 kg and must have a body mass index between 18 and 32&#xD;
             kg/m^2, inclusive&#xD;
&#xD;
          -  Participants must have a 12-lead electrocardiogram recorded at screening that is&#xD;
             normal for the appropriate age group and shows no abnormalities that will compromise&#xD;
             safety in this study&#xD;
&#xD;
          -  Participants must have no clinically significant findings on the clinical neurological&#xD;
             examinations at screening and at baseline or on the ophthalmic examination at&#xD;
             screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Nicotine use within 6 months before screening&#xD;
&#xD;
          -  Considered to be at a high risk of developing a stroke&#xD;
&#xD;
          -  Significant medical history of dizziness, blackouts, fainting, or vaso-vagal attacks&#xD;
&#xD;
          -  History of any significant ophthalmic disorder, including congenital, genetic or&#xD;
             acquired conditions affecting the retina or choroid&#xD;
&#xD;
          -  History of severe allergy or history of hypersensitivity to immunizations or&#xD;
             immunoglobulins&#xD;
&#xD;
          -  History of any significant psychiatric disorder&#xD;
&#xD;
          -  History of alcohol abuse&#xD;
&#xD;
          -  History of cancer within 5 years of screening&#xD;
&#xD;
          -  History of drug abuse&#xD;
&#xD;
          -  Any contraindication to Lumbar Puncture&#xD;
&#xD;
          -  Any clinically significant abnormality in ECG rhythm, conduction or morphology&#xD;
&#xD;
          -  Positive serologic findings at screening for human immunodeficiency virus (HIV)&#xD;
             antibodies, hepatitis B surface antigen, or hepatitis C virus antibodies&#xD;
&#xD;
          -  Use of prescription or non-prescription drugs&#xD;
&#xD;
          -  For female participants, a positive serum or urine pregnancy test result at screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeanelle Kam, MD, CPI</last_name>
    <role>Principal Investigator</role>
    <affiliation>Covance Dallas CRU, USA</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John E Blanchard, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Covance Madison CRU, USA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75247</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>United Kingdom</country>
  </removed_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>June 29, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>June 7, 2022</last_update_submitted>
  <last_update_submitted_qc>June 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy Volunteers</keyword>
  <keyword>Safety</keyword>
  <keyword>Tolerability</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Pharmacodynamics</keyword>
  <keyword>Immunogenicity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers can request access to anonymised 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</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 de-identified individual patient-level data in an approved sponsor 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>
  <!-- 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/NCT03272165
org study id: D6340C00001
nct id: NCT03272165
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a study of single ascending intravenous doses of MEDI1341 or placebo in up to 48
      healthy volunteers, aged 18 to 65 years. The study will include up to 6 planned cohorts; each
      cohort will comprise 8 participants.

      Each participant will receive a single 60 minute intravenous infusion of MEDI1341 or placebo
      and will undergo scheduled assessments over a period of 13 weeks.

      The main aim of the study is to assess the safety and tolerability of single doses of
      MEDI1341 in healthy volunteers.
This is a randomized, double-blind, placebo-controlled study of single ascending intravenous
      doses of MEDI1341 in male and nonfertile female healthy volunteers, aged 18 to 65 years.

      The study will include up to 6 planned cohorts; each cohort will comprise 8 participants.
      Within each cohort, 6 participants will be randomized to receive MEDI1341 and 2 will be
      randomized to receive placebo. A Safety Review Committee will review data from each cohort
      before progression to the next higher dose cohort occurs. On Day 1, each randomized
      participant will receive a single 60 minute intravenous infusion of MEDI1341 or placebo and
      will undergo scheduled safety, pharmacokinetic, pharmacodynamic, and immunogenicity
      assessments. Additional study assessments will occur on Days 2, 4, 8, 15, 22, 29, 43, 57, and
      92.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants are randomized to one of two groups within a cohort of 8 participants (N=6 MEDI1341; N=2 placebo)
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
time frame: Day 1 through 92 days after a single dose of study drug
description: An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
measure: Number of Participants With Abnormal Vital Signs, Physical and Neurological Examinations, and Body Weight Measurements Reported as TEAEs
time frame: Day 1 through 92 days after a single dose of study drug
description: Vital signs assessment included body temperature, respiration rate, pulse rate, and blood pressure. Participants with abnormal vital signs, physical and neurological examinations, and body weight measurements reported as TEAEs are reported.
measure: Change from Baseline in 12-Lead Electrocardiogram (ECG) Data in Paper and Digital Recordings (PR Interval, QRS Duration, QT Interval, QTcF Interval, and RR Interval)
time frame: 12-lead paper ECG: Baseline (Day -49) to Day 92; Digital ECG: Baseline (Day 1) to Day 92
description: Changes from baseline in 12-Lead ECG data in paper recordings (PR interval, QRS duration, QT interval, and QTcF interval) and digital recordings (PR interval, QRS duration, QT interval, QTcF interval, and RR interval) are reported.
measure: Change from Baseline in Heart Rate by 12-Lead ECG in Paper and Digital Recordings
time frame: 12-lead paper ECG: Baseline (Day -49) to Day 92; Digital ECG: Baseline (Day 1) to Day 92
description: Change from baseline in heart rate by 12-Lead ECG in paper and digital recordings are reported.
measure: Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs
time frame: Day 1 through 92 days after a single dose of study drug
description: Laboratory assessment included hematology, clinical chemistry, and urinalysis. Participants with abnormal laboratory parameters reported as TEAEs are reported.
measure: Number of Abnormal Findings for Ophthalmic Assessment (Ophthalmic Examination and Slit-lamp Examination) for Placebo and Cohorts 4 to 6 at Follow-up Visit
time frame: Follow-up Visit (Day 57)
description: Number of abnormal findings for ophthalmic assessment (ophthalmic examination and slit-lamp examination) at follow-up visit (Day 57) are reported.
measure: Intraocular Pressure at Screening for Placebo and Cohorts 4 to 6
time frame: Screening (Day -49)
description: Intraocular pressure at Screening (Day -49) is reported.
measure: Intraocular Pressure at Day 29 for Placebo and Cohorts 4 to 6
time frame: Day 29
description: Intraocular pressure at Day 29 is reported.
measure: Intraocular Pressure at Day 92 for Placebo and Cohorts 4 to 6
time frame: Day 92
description: Intraocular pressure at Day 92 is reported.
measure: Number of Participants With Injection Site Reactions
time frame: Day 1
description: Participants who had injection site reactions (bleeding, bruising, erythema, swelling, or induration) on Day 1 are reported.
measure: Visual Analogue Scale (VAS) Pain Score for Site Reaction Pain
time frame: Day 1 (within 24 hours after end of infusion)
description: The VAS (0 to 10 cm) was used to describe reaction site pain. The score 0 means 'no pain at all' and 10 score means 'worst pain imaginable'. The higher the VAS score, the greater the reaction site pain experienced.
measure: Number of Participants With Suicidal Ideation and Suicidal Behavior Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
time frame: Screening (Day -49) through 92 days after a single dose of study drug
description: The C-SSRS is a scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviours, and has a binary response (yes/no).
Suicidal Ideation: a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent.
Suicidal Behaviour: a "yes" answer to any of 5 suicidal behaviour questions: preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt (non-fatal), completed suicide.
measure: Number of Participants With Montreal Cognitive Assessment (MoCA) Total Score at Screening (Day -1)
time frame: Screening (Day -1)
description: The MoCA is s standardized cognitive screening tool for mild cognitive impairment and dementia. The total score was used as outcome measure and this score ranges from 0-31, with higher scores representing better cognitive ability and scores below 26 were considered as cognitive dysfunction.
measure: Number of Participants With MoCA Total Score at Day 92
time frame: Day 92
description: The MoCA is s standardized cognitive screening tool for mild cognitive impairment and dementia. The total score was used as outcome measure and this score ranges from 0-31, with higher scores representing better cognitive ability and scores below 26 were considered as cognitive dysfunction.
measure: Maximum Observed Serum Concentration (Cmax) of MEDI1341
time frame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
description: The Cmax of MEDI1341 is reported.
measure: Time to Maximum Serum Concentration (tmax) of MEDI1341
time frame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
description: The tmax of MEDI1341 is reported.
measure: Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC0-t) of MEDI1341
time frame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
description: The AUC0-t of MEDI1341 is reported.
measure: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of MEDI1341
time frame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
description: The AUC0-∞ of MEDI1341 is reported.
measure: Terminal Half-life (t1/2λz) of MEDI1341
time frame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
description: The t1/2λz of MEDI1341 is reported.
measure: Serum Clearance (CL) of MEDI1341
time frame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
description: The CL of MEDI1341 is reported.
measure: Volume of Distribution at Steady State (Vss) of MEDI1341
time frame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
description: The Vss of MEDI1341 is reported.
measure: Mean Residence Time (MRT) of MEDI1341
time frame: Day 1 (predose; 0 minute and 8 and 24 hours at the end of infusion), and Days 4, 8, 15, 22, 29, 43, 57, and 92
description: The MRT of MEDI1341 is reported.
measure: Percentage Change From Baseline in Plasma Concentrations of Total α-synuclein
time frame: Baseline (Day 1 predose) through Day 92
description: Maximum change from baseline through Day 92 and change from baseline at Day 92 in plasma concentrations of total α-synuclein are reported.
measure: Percentage Change From Baseline in Cerebrospinal Fluid Concentrations of Free α-synuclein
time frame: Baseline (Day 1 predose) and Day 29
description: Change from baseline in cerebrospinal fluid concentrations of free α-synuclein is reported.
measure: Percentage of Participants With Positive Antidrug Antibodies (ADAs) to MEDI1341 by Titer Levels at Day 92
time frame: Day 92
description: Percentage of participants with positive ADAs to MEDI1341 by titer levels are reported.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive a single intravenous (IV) infusion of placebo matched to MEDI1341 and will be followed up for 13 weeks.
arm group label: Cohort 1: MEDI1341 Dose 1
arm group type: Experimental
description: Participants will receive a single IV infusion of MEDI1341 Dose 1 and will be followed up for 13 weeks.
arm group label: Cohort 2: MEDI1341 Dose 2
arm group type: Experimental
description: Participants will receive a single IV infusion of MEDI1341 Dose 2 and will be followed up for 13 weeks.
arm group label: Cohort 3: MEDI1341 Dose 3
arm group type: Experimental
description: Participants will receive a single IV infusion of MEDI1341 Dose 3 and will be followed up for 13 weeks.
arm group label: Cohort 4: MEDI1341 Dose 4
arm group type: Experimental
description: Participants will receive a single IV infusion of MEDI1341 Dose 4 and will be followed up for 13 weeks.
arm group label: Cohort 5: MEDI1341 Dose 5
arm group type: Experimental
description: Participants will receive a single IV infusion of MEDI1341 Dose 5 and will be followed up for 13 weeks.
arm group label: Cohort 6: MEDI1341 Dose 6
arm group type: Experimental
description: Participants will receive a single IV infusion of MEDI1341 Dose 6 and will be followed up for 13 weeks.
intervention type: Drug
intervention name: MEDI1341
description: Participants will receive IV infusion of MEDI1341 doses as stated in the arms' description.
arm group label: Cohort 1: MEDI1341 Dose 1
arm group label: Cohort 2: MEDI1341 Dose 2
arm group label: Cohort 3: MEDI1341 Dose 3
arm group label: Cohort 4: MEDI1341 Dose 4
arm group label: Cohort 5: MEDI1341 Dose 5
arm group label: Cohort 6: MEDI1341 Dose 6
other name: TAK-341
intervention type: Drug
intervention name: Placebo
description: Participants will receive IV infusion of placebo matched to MEDI1341.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jeanelle Kam, MD, CPI
role: Principal Investigator
affiliation: Covance Dallas CRU, USA
last name: John E Blanchard, MD
role: Principal Investigator
affiliation: Covance Madison CRU, USA
facility: 
facility: 
country: United States
country: United Kingdom
responsible party type: Sponsor
mesh term: Parkinson Disease
sharing ipd: Yes
ipd description: Qualified researchers can request access to anonymised 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
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 de-identified individual patient-level data in an approved sponsor 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